Welcome back, thank you for joining us this morning for part two of Investor Day, where we will cover the remainder of our key R&D programs. Today, we'll hear from our immunology and inflammation, oncology, and rare disease teams, then we'll end with a segment on our COVID vaccine and antiviral programs. As a reminder, presentations at today's session include forward-looking statements about, among other things, our anticipated future operating and financial performance, business plans and prospects, and expectations for our product pipeline, in-line products, and product candidates. By their nature, all statements about future events and expectations for our pipeline products are forward-looking. Each forward-looking statement contained in these presentations is subject to risks and uncertainties that could cause actual results to differ materially from those in such statements.
Additional information regarding these factors appears in the slide entitled Forward-Looking Statements and Other Notices and under Risk Factors in our Form 10-K and Form 10-Q. Forward-looking statements in these presentations speak only as of the original date of the presentation. We undertake no obligation to update or revise any of these statements. As was the case with yesterday's presentations, the slides that will be presented during this call will be posted on pfizer.com/investors after each session. You can also find today's speaker bios and the day's agenda on a separate tab on that site. As with the format yesterday, there will be time for Q&A via the operator following each business unit's presentation. Before we dive into our I&I programs, we'd first like to share a video featuring Steve, an atopic dermatitis patient.
[Presentation]
[Presentation]
Now, I would like to turn it over to our I&I leadership team.
That was Steve. I met Steve late last year, and his story reminds us of how inflammatory diseases are so underappreciated. It's so easy to fail to understand the suffering. We hear things like, "Well, it's just a bit of swelling. It's a digestive issue. It's just a rash." It isn't. It's a life blighted by inflammation, affecting self-confidence, relationships, employment prospects, and limiting daily activities. Steve reminds us, too, of the transformative potential of modern medicines. After a life of living by the ocean, when he found a treatment that really worked for him, he went into the sea for the first time in his 50s. Good morning, everyone. I'm Richard Blackburn, and together with my colleagues, Mike Corbo and Mike Vincent, we lead the Inflammation & Immunology category here at Pfizer.
Over the next decade, we will bring breakthroughs, not just for people like Steve with skin conditions, but many others with gastroenterological and rheumatological ones as well. Now, maybe you think of us as tenured in this therapeutic area, given our involvement with Enbrel since the 1990s. Maybe you also see us as innovators, given our launch of XELJANZ, the first JAK inhibitor for rheumatoid arthritis back in 2012. Well, the time has now come to also see us as leaders in I&I research and development based on the strength and breadth of our pipeline and the exciting range of treatments that we expect to make available in the coming years. We're confident about our potential to change lives with this portfolio, and we want to share some of the reasons why. I really want to start, though, with two simple messages.
The unmet need in inflammatory disease is enormous, therefore is the opportunity for innovative new medicines. Secondly, delivering for patients depends on matching the right treatment to the right condition. Firstly, the unmet need. Let's just consider the U.S. Over two million people suffer with inflammatory bowel disease, three million with rheumatoid arthritis, and over 30 million people with atopic dermatitis. That's just for the U.S. population. Obviously, there are millions more suffering worldwide. Some of those conditions, such as rheumatoid arthritis and IBD, are widely treated with biologics and other advanced agents. Today, a huge proportion of patients are still unable to achieve remission. Some other conditions, such as alopecia areata, today have no licensed therapies anywhere. That's another autoimmune disease characterized by hair loss.
More than a million people live with moderate to severe alopecia areata in the U.S. alone, and it can have a profound impact on people's quality of life and emotional well-being, sometimes even leading to severe depression. I'm excited that we're on track to potentially bring a first-ever FDA-approved therapy for this condition. Let's go back to those 30 million U.S. patients with atopic dermatitis. One out of three of those patients has moderate to severe disease. Today, out of the 6.5 million adults living with moderate to severe AD, only 2.6 million are treated with a systemic therapy, and as many as 1.6 million are uncontrolled. Now, patients' expectations have rightly been raised in the past couple of years following the introduction of new treatments. Not all patients receiving advanced therapies achieve clear skin, so more alternatives are needed.
There's also an opportunity to focus on the defining symptom of itch, which is a top priority for patients. You heard from Steve about how everything starts with itch. He's not alone in that. Research has shown that itch is the most bothersome symptom for the majority of patients with AD and the one that they'd most like addressed with treatment. Now, my second key message is that as more therapies become available, finding solutions for the remaining needs of patients demands us to look at multiple options. There's no such thing as the right medicine for everyone. There is no silver bullet. Now, our aim today is not to take you through the whole pipeline here, but across rheumatology, gastroenterology, and dermatology, we're progressing multiple projects. We're studying five new immunokinase alone and in combinations, in oral and topical formulations across 10 diseases.
Our research efforts extend well beyond JAKs with three biologics, each with novel mechanisms in phase II. This year alone, we have four proof-of-concept readouts featuring three separate molecules. Our approach is not one of developing a single molecule for multiple different indications. It's honestly unlikely that any medicine will represent a breakthrough option in, let's say, six different diseases. Our approach is to purposefully match the right molecule to the disease where we believe it can make the most difference. What emerges for patients from our pipeline will only be breakthroughs. We're setting a high bar for what will move forward. We're not interested in just another option for RA. We'll only bring to patients a medicine or a combination of medicines that will significantly increase the percentage of patients achieving remission compared to current best care.
We'll only launch a medicine in atopic dermatitis if it meets needs that aren't fully addressed by what's available today. In a moment, Mike Vincent will tell you more about our purposeful approach to match the right treatment to the right condition. He'll illustrate it with just two examples from our phase II and III immunokinase portfolio. Mike Corbo will talk in depth about abrocitinib, our exciting phase III compound that has FDA breakthrough designation for moderate to severe atopic dermatitis. I'll close my remarks by saying that we are highly optimistic that we're poised to help hundreds of thousands more people like Steve in the years ahead. Here's our Chief Scientific Officer for I&I, Dr. Mike Vincent. Mike.
Thank you, Richard. You just heard about the breadth and depth of our pipeline, but let me focus in on our immunokinase portfolio to illustrate our overarching scientific approach. Our strategy is to purposefully match candidates with unique selectivity profiles with the disease or diseases where they hold the greatest potential to relieve suffering. One point I want to leave you with today is our scientific perspective on differing cytokine inhibitory profiles within the JAK class. As illustrated by the distinctive shapes in each of these spider grams, we believe these unique selectivity profiles will translate into differing efficacy and safety profiles across diseases. Our scientific view is now supported by a growing body of clinical data, some of which we'll share with you today.
JAK pathways play an important role in inflammatory processes involved in signaling for over 50 cytokines and growth factors, many of which drive immune-mediated diseases. For each of our JAK inhibitors, we have a molecule whose design corresponds not just to broad immunosuppression, but to the function driven by specific cytokines and corresponding immune cells that drive disease. For example, in contrast to an agent that inhibits only IL-4 and IL-13, our JAK1 inhibitor, abrocitinib, also targets IL-31 which is a cytokine that's believed to drive itch that torments AD patients and is generally regarded as the most burdensome aspect of their disease. Our JAK3/TEC inhibitor, ritlecitinib, has a unique activity, shown at six o'clock in the spider gram, of blocking CD8 T-cell killing, which is widely believed to be a key mechanism in the immune system's attack on the hair follicles in alopecia areata.
Our brepocitinib molecule, which I'll share some new data on today, covers some of the same cytokines I mentioned a moment ago that are associated with AD, but also inhibits IL-23, which is a key cytokine driving Th17 inflammation, commonly associated with psoriasis. You'll notice the molecule on the right does not have a spider gram, which is because there's zero overlap with JAK-dependent cytokines. Instead, IRAK4 is downstream of a range of receptors that collectively trigger inflammation in response to danger signals, as you might find in an inflamed joint. This was the first IRAK inhibitor to enter the clinic and the first and only to show efficacy in a phase II study in RA. We have just initiated a phase II trial in RA in combination with tofacitinib or ritlecitinib.
Now to provide some evidence that our strategy is sound, we'll show a few examples of recent data for investigational molecules that, if approved, have the potential to be breakthroughs for patients. I'd first like to turn to our ritlecitinib program for alopecia areata, which has been granted breakthrough designation by the FDA and could potentially be the first-ever approved treatment for this disease. This slide shows the data we first presented at EADV in 2018 and formed part of the data package on which the FDA granted ritlecitinib breakthrough therapy designation. You can see the hair regrowth of the patients shown in the study pictures at 12 and 24 weeks of treatment.
Positive phase II data showed that the use of ritlecitinib resulted in improved hair regrowth on the scalp relative to baseline at week 24, as measured by the severity of alopecia tool, or SALT, which is scored on a 100-point scale. In addition to meeting the primary efficacy endpoint, ritlecitinib also met all the secondary endpoints in the study and was well-tolerated. Ritlecitinib is currently in a pivotal phase III clinical trial for the treatment of patients with moderate to severe alopecia areata. We expect top-line results in the third quarter of 2021 and a potential filing by early 2022. As a result, we could bring the first-ever approved treatment for alopecia. I'd now like to transition to another exciting molecule that we're looking to advance to phase III, brepocitinib. It's important to emphasize here that matching the right molecule to the right patient includes understanding its formulation properties.
We recognize that brepocitinib, our TYK2/JAK1 inhibitor, could be delivered in a convenient daily topical cream formulation, creating a potential novel topical treatment option for patients with a variety of inflammatory skin diseases. The diagram on the left illustrates a couple of the key activities of brepocitinib. The inhibition of TYK2 blocks the Th17 axis, which is believed to be important in psoriasis and some forms of atopic dermatitis. The inhibition of JAK1 blocks the Th2 axis, which is believed to be a dominant pathway in atopic dermatitis. Our phase II data for topical brepocitinib in patients with mild to moderate AD indicated a strong dose-dependent efficacy signal, with 42% of the patients in the 3% once-daily cohort achieving EASI 90 by week six, which is really encouraging given that EASI 90 reflects the 90% reduction in the score measuring an AD patient's inflamed skin.
These data illustrate the concept I described on the spider gram plot a few slides ago. That this particular selectivity profile shows the potential to provide meaningful benefit to patients with mild to moderate atopic dermatitis. I should note that we have an ongoing phase II psoriasis study to explore the full versatility of this agent's diverse cytokine inhibitory profile. That benefit is further illustrated by these images. Here we see a patient journey over six weeks of using topical brepocitinib at the 1% dose, a 20-year-old white male. After two weeks, we saw a 50% improvement in the EASI score. After six weeks, we saw an 83% decrease in EASI score from baseline, with almost no visible symptoms.
Now I'll hand it over to Dr. Mike Corbo, our Chief Development Officer, to continue our discussion on atopic dermatitis, and he'll walk you through our abrocitinib development program.
Thanks, Mike. Thank you for sharing some of the new data from our emerging pipeline. As you may be able to surmise, we are committed to the patients that we serve across our portfolio. In AD alone, we've introduced the first topical PDE4 inhibitor, what we hope to be the first and only dual-acting JAK1 topical, and potentially the first and only dermatology-specific JAK1 inhibitor in atopic dermatitis. This is the right way to address our patients' needs. While you saw some of the pictures for mild to moderate AD patients in Mike's presentation, this is what a severe patient looks like. As you've heard today, living with AD is not easy. This is the type of patient we hope to treat with abrocitinib. We have a highly focused development plan for abrocitinib in AD.
The core program consists of two placebo-controlled monotherapy studies and one placebo-controlled active comparator study. The results from these studies form the core basis of efficacy for our filing. We now have the results from all three of the efficacy studies. We have accumulated the required long-term safety data and have submitted the NDA to the FDA. We have also completed the JADE TEEN study, which met all of its primary endpoints. Later this year, we will receive top-line data from JADE REGIMEN, which should be helpful in understanding dose flexibility in the future. We will now look at some of the relevant data from JADE MONO-1 and MONO-2 and COMPARE. As you have already seen the primary endpoints for the 12-week MONO-1 and MONO-2 studies, we're going to focus on raising the bar higher. First, looking at the EASI-90 over time.
Basically, this looks at a 90% improvement in signs and symptoms. Here, we have pooled the data from both monotherapy studies since the trial designs and results were very similar. You will notice a very rapid onset and substantial portion of patients achieving an EASI-90 by week 12 for both the 200 mg once daily dose in red and the 100 mg dose in dark blue. Placebo is in gray. Importantly, in our long-term open label safety extension, using as observed data, we continue to see improvements in signs and symptoms through week 24. As you've heard earlier directly from a patient, the one symptom that is most bothersome and worrisome for patients is pruritus or itch.
In that regard, we can look at the improvement in the itch or pruritus score over time, again using MONO-1 and MONO-2 pooled data. Looking over the first two weeks, you can see a very rapid onset beginning as early as day two, after just one dose, for both the 200 milligram dose in red and the 100 mg in dark blue. Again, placebo is in gray. Importantly, these results are sustained throughout the 12-week duration of this study. Beyond just being fast, abrocitinib has an effect on itch that's also durable, which is critically important to our patients. While the overall safety profile has already been presented, we thought we would focus on some events of special interest from MONO-1 and MONO-2. As you will note, we did see a dose-dependent increase in nausea.
The majority of these cases were mild to moderate and occurred shortly after dosage initiation and were self-limiting. One thing we have noted is that when abrocitinib is taken with food, the nausea can be mitigated. As expected in this population and with JAK inhibition, we did see herpetic infections, including herpes simplex and herpes zoster, which were dose dependent. The overall safety profile is well understood in the clinical trial environment to date, and many of these events can be managed with well-established mitigation approaches. Of note, we have not seen an increase in serious infections at this point in time in the development program. Moving on to COMPARE. As you are aware, we reported top-line results from this study earlier this year. This was a four-arm randomized placebo-controlled double-dummy study. The study allowed for concomitant topical steroid use consistent with dupilumab labeling.
The study met all of its primary endpoints. A key secondary endpoint, abrocitinib at 200 mg was superior to dupilumab at two weeks in the improvement of itch. Pruritus is the primary concern that patients have with atopic dermatitis, and we're encouraged to see a rapid and sustained response addressing this key feature of the disease. As we have said previously, we always need to strive to do better for patients beyond the standard measures. We can look at some higher-level responses from the secondary analyses next. We need to always strive to do better. One way to look at this would be to look at resolution of itch, not just reduction, but resolution, and looking at it just after two weeks.
Resolution of itch is defined as a score of a 0 or a 1 in the PP-NRS score, so essentially complete relief by week two. Note that the baseline mean score for patients in this study was 7, we're talking about a very substantial improvement. Moving left to right, we can see that the placebo had 4.6% of patients with resolution of itch, 100 milligram abrocitinib around 9%, the 200 milligram abrocitinib dose at 15%, and 4.6% in dupilumab. If you can think about this is resolution of itch in just two weeks in moderate to severe patients. This is the goal we need to strive for. Now let's look at the EASI-90 over time in JADE COMPARE. Again, focusing on 90% improvement. We can see the results from abrocitinib 200 milligram in red with a substantial proportion of patients rapidly reaching an EASI-90.
Nearly 50% of patients achieve this level of relief by week 16. 100 mg in dark blue also has a rapid onset. Dupilumab is in green, which appears similar to the 100 mg by week 16. Again, placebo is in gray. We are encouraged by these results. We've used these data to design an additional head-to-head study, which has already initiated. Turning to safety, we've observed a profile for both doses of abrocitinib that was consistent with our prior monotherapy studies. Qualitatively, the types of events seen in the abrocitinib arm were consistent with the monotherapy studies. The dupilumab arm was similar to published literature and product labeling. While it's always good to look at data, it's more important to understand what do these numbers actually mean when it comes to a patient.
If you recall the picture of the gentleman that I showed you in the beginning of this section of the presentation, this is a patient with severe AD. Well, he was a participant in the 200 milligram arm in the MONO-2 study. Well, this is what an EASI-90- plus responder looks like. This is the reason we do what we do and why we're excited about abrocitinib's breakthrough potential. I hope that we've given you an appreciation for the commitment and the dedication that we have at I&I for our patients. I'll now turn it back to Richard for some closing comments.
What Mike just shared is a genuine potential breakthrough for patients with moderate to severe atopic dermatitis. While recent product introductions for these patients have represented real advances, the unmet need in AD remains enormous. Today, only 40% of suitable patients are receiving an advanced treatment, and as new systemic treatment options become available, we expect more usage. Physicians and patients have told us that rapid efficacy against itch, dose flexibility, and the convenience of oral administration are highly attractive. Backed by the experience, relationships, geographic reach, and resources of Pfizer, we are confident we can make a significant impact. Abrocitinib represents just the first of what's to come. You've seen also why ritlecitinib is a potential breakthrough for alopecia and potentially for vitiligo too.
Even with conservative assumptions about diagnosis and treatment rates and usage of our new medicines, we can model significant potential global peak revenues for both. Beyond that, we intend to bring forward additional breakthroughs with a significant remaining unmet need in a range of other conditions, always with our criterion that nothing comes to patients that doesn't offer an advantage over what is currently available. As a reminder, five immunokinases, oral and topical, being researched for 10 separate conditions, as well as three other modes of action in phase II. We have the potential to help across the landscape of inflammatory diseases. Our purpose is to change lives, and this portfolio, we believe, will deliver the power of that purpose. I turn it back to Chuck to facilitate the question and answer session.
Thanks, Richard. Okay, now our I&I leadership team is available to answer your questions about their pipeline. Operator, can we please now poll for questions for the I&I team?
To ask a question, please press star one on your telephone keypad. To withdraw your question, press the pound key. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Umer Raffat from Evercore. Umer, your line is open. You may proceed with your question.
Hi, this is Bo for Umer. Thank you for taking our questions. Just a quick one on the abrocitinib COMPARE data. It's curious to see that the SAE rate for the 200 mg is higher than 100 mg, but the duration, the discontinuation is actually lower than the lower dose. Just curious on the general thoughts on how do you see the duration of treatment on abrocitinib for the atopic derm patients. Thank you.
Okay. Thanks for the question, Umer. I'm going to hand over to Mike Corbo to address the specific question about from the COMPARE data, and then maybe I'll just make a couple of follow-up comments. Mike, do you want to address the question about the dosage there?
Sure. Thank you for the question. Thank you, Richard. In the COMPARE data or the 200 mg data, there were really not a large difference with SAEs across the board. In general, I think we see a relatively low SAE rate across both the 100 mg and the 200 mg. These do not seem to increase over time, as you were talking about duration. I think primarily what we do see are obviously some initial nausea, vomiting in the beginning, which does fade over time. As far as SAEs go, we do not see that increasing over the time and shouldn't impact the duration of therapy. Hopefully, that addresses your question. Richard, I can go back to you.
Yes. I think you've covered it really, Mike. We see abrocitinib as an exciting new option for patients. You've heard in our presentation just how significant the unmet need is and how great the need for new options are. We see abrocitinib as providing physicians exactly what they're looking for, a rapid onset of action, profound and early impact on itch, and a sustained efficacy over time. We see this as an ideal agent for long-term use in patients with moderate to severe disease. Hope that covers the question, and maybe we can go to the next one.
Your next question comes from Geoff Meacham from Bank of America.
Hi, guys. Thanks for the question. Just another one on abrocitinib, but more higher level. I just wanted to ask on the commercial positioning, clearly, the JAK class is pretty crowded. Wanted to ask you how you think, what would you say the biggest attribute, the differentiation point is? When you look beyond atopic derm, does that same sort of risk-benefit profile also hold with respect to differentiation? Thank you.
Okay, Geoff. Thanks for the question. You said that the JAK space is becoming crowded. I guess the first thing that I would say is that the fact that other companies are investigating JAK inhibitors in atopic dermatitis and indeed other conditions, rather reinforces our confidence in the value of this mechanism. It's, I think, too early for us to make any comments about potential differentiation between JAK inhibitors in atopic dermatitis. While data is emerging for other compounds, there are no comparative studies available at this point, and probably too many differences between development programs to be able to make a definitive statement. I will pause here and ask if Mike Corbo would just like to make a couple of comments about potential differences, and then I'll come back and talk about a bit more on the commercial position. Mike?
Okay. Thanks, Richard, and thanks, Geoff. I think in general, it's going to be hard, as Richard said, to be able to show any kind of an understanding without doing a head-to-head study for differentiation. I think if you go back to our development philosophy and how we're developing the variety of different JAKs that we have in our portfolio, you can see that we are being very specific. For abrocitinib, it is strictly a derm molecule. Its next hopeful expansion will be within the derm space. From a differentiation perspective, abro will be dedicated to dermatology. Again, as we look at our profile, we're lucky that we have so many different varieties of JAK profiling. It allows us to look at different therapeutic areas a little bit more focused. That way we can direct our benefit risk to a specific therapeutic area. Richard?
Yeah. I think the one thing I would want to add is, in your question, you said it's a crowded space between JAK inhibitors. One thing I'd just like you to really remember from our presentation is just how huge the unmet need is, particularly in moderate to severe atopic dermatitis. There are 30 million patients in the U.S. suffering, maybe 27 million that are aged over 12. Only around half of them are treated with a prescription medicine today, and a small proportion of those get a systemic treatment, less than 20%. We see an enormous opportunity for a great increase in the systemic treatment of this condition as more new agents become available. One of the reasons we're confident about that is, of course, that's exactly what we've seen in the psoriasis market.
The availability of new, effective systemic agents leading to a significant increase in the proportion of patients treated. We think that same revolution is coming to atopic dermatitis. I guess my point is that this isn't a zero-sum game between new agents competing for a very small number of patients. Actually, the opportunity is to greatly expand the effective treatments. We're confident that that's going to happen, and we're introducing abrocitinib, we think at exactly the right time, the right profile coming into the market at the right time. I hope that covers the question. Thanks very much. Operator, maybe we can go to the next one.
Your next question comes from Steve Scala from Cowen.
Thank you. I apologize if I missed this. I had some webcast issues. The topical JAK inhibitor is scheduled for launch in atopic dermatitis in 2025. This is four years post a possible launch of topical ruxolitinib by Incyte. How is Pfizer seeking to differentiate? Will the topical JAK be looked at in vitiligo? A second question, which I was unable to ask yesterday, so allow me to ask it now. The 6%+ revenue growth for the company overall, yesterday it was said to be risk-adjusted. When Pfizer has described growth in the past, the words risk adjustment don't seem to have been used. Is this a new disclosure, and if so, what does it imply about Pfizer's confidence in the outlook? Thank you.
Okay. Steve, thanks for the two questions. The second one obviously is not specific to the inflammation immunology portfolio, so I'll just pause and ask if, Chuck, you'd like to take that one first, and then we'll deal with topical abrocitinib.
Thanks, Richard. Steve, what we were showing yesterday on an unrisk-adjusted basis was we showed two numbers. We showed a total value of the pipeline that was $35 billion to $40 billion, again, with the caveat that not all of those assets hit peak sales, of course, in the same year. That's an amalgamation of all the assets and their peak sales in each given year. The unrisk-adjusted number we showed on Angela's slide when we showed what we need to get to achieve the 6% growth, we showed that we had a very large buffer, well beyond the 6% CAGR on an unrisk-adjusted basis, and then we risk-adjusted it back down to show you how we hit the 6%.
I think the main message here is this is not a story about just one or two assets, either in market or in the pipeline that need to hit. It's a broad portfolio approach, both on the in-market programs that Angela went through and then within some of the pipeline programs here. Yes, the disclosure was new on the value on an unrisk-adjusted basis, Steve. We had not put those numbers out up until yesterday. You're correct, up to now, we've been saying the 6% is risk adjusted. We showed you, basically gave you some context around the confidence intervals, in a sense, on the risk adjustment rate. I think that's the key takeaway. We have a lot of cushion, and we have multiple programs all potentially contributing to this growth over that time period.
Hope that helps, and I'll turn it back to Richard now for your other questions.
Thank you, Chuck. Steve, your other question related to topical abrocitinib, and I think probably both Mikes will want to comment on that. Mike Vincent, maybe we can go to you first and just talk about what we see and the question relating to our profile versus for the Incyte product. Mike, you may want to add a little bit. Mike Vincent first.
Thanks, Richard, thanks for the question. We think there remains an incredible need for other topical formulations for patients with mild to moderate disease, where symptom relief can be achieved via direct action on the skin, minimizing systemic exposure. We're aware of competitor data. We haven't seen all of that yet, but we think that the EASI-90 responses we've seen with topical brepocitinib are very strong in the 40% range with a single daily application. The other feature of ritlecitinib that we like and think will add to the differentiation is its ability to hit multiple inflammatory pathways like the Th17 axis, which we think will be useful in psoriasis. Currently, we have an ongoing study in psoriasis in addition to the AD program. We haven't yet initiated work in vitiligo , but that's something that we'll certainly consider in the future.
Maybe I'll hand it to Mike Corbo to talk a little bit about the differentiation strategy.
Okay. Thanks, Mike, and thanks for your question, Steve. In addition to what Mike said, we do think given its dual activity, that we do have the potential to work effectively in the Th17 phenotype that you do see in AD. That's one differentiator, as Mike mentioned also, QD dosing is also a potential advantage. We also don't anticipate any limitations in body surface area, with application of the drug. We also intend to start our program with children from the beginning, if we can do that from a regulatory perspective. The other key feature, I think of the late-stage development plan that's important is that we will be including long-term dosing data. That's from an efficacy perspective. We'll look at posology out through one year from the very beginning. We do think that's going to be an important feature of the development program.
As Mike mentioned also, having the ability to potentially be treating psoriasis will further differentiate us from rux.
Great. Thank you to both of you. Steve, I hope that addresses the question. Operator, perhaps we can go to the next one.
Your next question comes from Navin Jacob from UBS.
Hi. Thanks so much for taking the question. TYK2 JAK1 looks very interesting, likely will show some very good efficacy. Just wondering about the pathway, the TYK2 being some investigators that we've talked to, experts have suggested, that regulators may view TYK2 as part of the JAK class, and as such, there's potential for a broad-based class warning. I realize it's very early to perhaps be having those kind of discussions with regulators, but how do you view that potential for a broad-based class warning if this was to get to the market? Then on alopecia areata, very interesting data that you're showing.
Wondering if you could give some color on that marketplace, what the dynamics are, what percentage of patients fall into managed care versus Medicare, as well as what level of pricing power we should think you can achieve there. What are some of the comps that you're looking at? Thanks so much.
Great, Navin. Thank you. Thanks. Two questions there. I think for the question on ritlecitinib to JAK1, we'll go to Mike Vincent, and then I'll come back and talk about the potential that we see for ritlecitinib in alopecia. Mike, over to you first.
Yeah. Thanks for the question. I think it's really important to remember that when you're talking about JAK inhibitors, you're talking about four distinct enzymes. Unlike the case with TNF inhibitors or IL-6 inhibitors, it's not really a class. Maybe just to follow up on that example, most of the JAK1 inhibitors have pretty profound inhibitory effects on IL-6. Yet, if you looked at the graph on ritlecitinib, we have no IL-6 coverage at all. To expect extrapolation of one label for a particular selectivity profile to another molecule that has a different selectivity profile and inhibits a different group of cytokines, we think is probably not the most scientific approach, and we don't think that regulators will take that approach in any kind of a programmatic way.
We think you really have to look at each individual molecule, the safety and efficacy profile, and the population you studied. We think that's how regulators will decide on safety labeling. Let me hand it back to Mike, I guess. Or maybe it's you, Richard.
Yeah, I'll talk a little bit about the marketplace for alopecia. A condition that is not well understood by many people today. A very significant autoimmune disease. Maybe it is missed as a cosmetic condition. That's absolutely not the case. As you heard in the presentation, it has a profound impact on patients' well-being. It affects self-esteem. Patients often experience anxiety and depression. Very much a devastating disease that today really has no licensed treatment options anywhere in the world. Patients today either really receive no medical care, or they receive off-label treatments which are either ineffective or particularly unpleasant. Multiple steroid injections into the scalp, for instance. We're really excited about the possibility of bringing to market an agent which will be effective and well-tolerated. Has the potential to really revolutionize treatment for this group of patients.
What may surprise you is how many of them there are. An estimated 1%-2% of the population in the U.S. suffers from alopecia. Maybe three million people, of which perhaps one million have moderate to severe disease. It's a significant number, and we think that upwards of 35%-40% of patients may eventually be receiving an advanced treatment, so a significant opportunity. I think behind your question, there's a question around will payers be willing to reimburse this condition? We think there is a need for education on the burden of disease and the benefits of treatment. Those conversations are already starting. We understand the need to invest in education for a new market area like this. We have a lot of experience and track record at Pfizer of launching new treatments into new markets.
A little early to speculate on pricing and so on, but I think I can tell you with some confidence that we think we'll be able to bring this to market with good access from payers around the world. I hope that kind of gives you enough at this point. Thanks for the question, Navin. Operator, I think we've got time for one more.
The next question comes from Andrew Baum from Citi.
Thank you. A couple of questions, please. You've highlighted the fragmented addressing each sub-market with its own JAK inhibitor. In the commercial setting, arguably part of the success of HUMIRA at delaying the adoption of some of the novel therapies, including your own XELJANZ, has been the rebates, the sizable rebates, having one drug addressing multiple indications has delivered. How do you anticipate addressing this going forward? Are you betting that the rebate system will evolve by the time these drugs reach the market, or be driven, you believe, by more compelling data, greater familiarity with oral JAKs? That's the first question. The second question is, obviously oncology has very successfully adopted precision medicine, identifying subgroup of patients who are more responsive to a particular mechanism within a broader phenotype.
To what extent could you think adopt the same approach with autoimmune diseases, i.e., subgroups of patients who may be particularly JAK1 or IRAK or whatever, and is there a role for some type of basket trial in order to try and segment these individual patient groups?
Andrew. Thanks for those two questions. Let me deal with the first one. I'll ask Mike Vincent to pick up on the second one. Yeah, I think you hit on the key thesis really behind our development strategy, which is that as more new medicines come to market, what's going to really matter for patients and frankly for payers as well therefore is differentiation. Are we bringing something which offers to patients a benefit that is not currently available? We think the very best way of doing that is to develop a broad range of candidates and match purposefully the right one to the right disease. We think that that's the best way to bring value to patients. Ultimately, we think that that will be recognized by payers.
Of course, the rebate system continues to be a challenge with any new product introduction, but I think you've seen our willingness elsewhere in our portfolio to make the appropriate investments to make sure that we secure commercial access for our products. As our portfolio grows in I&I, then the options obviously for contracting become wider as well. That's a brief answer to the question. I want to give Mike enough time just to cover the second question about precision medicine. Thanks, Mike.
Thanks, Richard, and thanks for the question. I think it's an astute observation, and indeed, I think we do see the direction of travel in autoimmune diseases reflecting what's been observed in oncology diseases. Maybe just to point out a couple of examples, we know now that diseases where TYK2 might be particularly useful involve the Th17 axis, IL-23 and IL-17 signaling seem to be important in driving psoriasis, psoriatic arthritis, ankylosing spondylitis as prototypic spondyloarthropathies. We also think of our JAK3 inhibitor as a molecule whereby its mechanism inhibiting cell killing of CD8 cells may be particularly valuable for diseases like alopecia, where sensitive stem cells in the hair follicles are killed by immune cells, and vitiligo may be a similar example. We do see a similar paradigm emerging in autoimmune diseases, and we think our strategy really plays well to that change in the field.
Thanks for the question.
Thanks, Mike, and I'm afraid that's all we've got time for. Thanks for the questions, and thanks to everyone for listening. I'll pass this back to Chuck.
Great. Thanks, Richard. Thanks to the triad for taking the questions. Now we're going to transition to our Rare Disease programs, and before we dive into the Rare Disease area, we'd first like to share a video featuring Jake Marrazzo, a DMD patient.
[Presentation]
[Presentation] .
Now I'd like to turn it over to our Rare Disease Leadership team.
There are approximately 7,000 rare diseases in the world, and fewer than 5% have an approved therapy on market. Further, it is important to note that 80% of rare diseases are genetic, and greater than 50% impact children. Although individually rare, with each disease impacting under 200,000 people in the U.S., and less than one in every 2,000 people in Europe, rare diseases are collectively common, impacting approximately 400 million patients worldwide. We are pleased to see that the global community is responding in a robust manner by engaging and investing in an increasing number of clinical trials, which leads to more robust pipelines and potential double-digit growth for the global rare disease market. The high unmet need, coupled with significant investments in this space, have created both a hopeful environment for patients and an attractive one for investors.
Pfizer Rare Disease aspires to be the world's leading innovator in Rare Disease by pioneering breakthroughs that have a profound impact on the lives of underserved patient populations with unmet needs. Hi, my name is Suneet Varma, and I'm the President of our global Rare Disease Business Unit. I, along with my R&D partners, am pleased to have the opportunity to share with you our excitement for Pfizer's growing Rare Disease unit, anchored by VYNDAQEL, and the transformational pipeline we have built, which includes a robust set of gene therapy programs and underlying capabilities. By way of brief background, I have more than 25 years in the industry, and I've been with Pfizer for more than a decade, having come over from Wyeth in 2009. I lead the Rare Disease business along with Brenda Cooperstone, our Chief Development Officer, and Seng Cheng, our Chief Scientific Officer.
Brenda and Seng will briefly introduce themselves to you during this presentation. You also have access to all of our bios. The rare disease unit was formally established in 2015 in order to further pursue our aspiration of leadership in this space after having made key investments internally in tafamidis and externally with Spark in 2014, Bamboo in 2016, Sangamo in 2017, and Vivet just last year in 2019. We are incredibly proud of the progress we've made to date and for the exciting future ahead. Let me share with you our approach to rare disease leadership. We are building on a leading in-line portfolio by extending our current positions in rare hematology and rare endocrine, where we have a 30-year heritage that includes well-known brands such as BeneFIX and GENOTROPIN, upon which we have now built a pipeline to bolster our presence even further.
Second, we are expanding into two new additional therapeutic areas, rare cardiology and rare neurology. In cardiology, VYNDAQEL will continue to drive growth in the U.S., Japan, and Germany, and we have many more international launches planned. Further, we have another treatment in phase III today that will augment this franchise. We are also excited to launch new therapies in neurology with our highly anticipated DMD gene therapy program, for which we'll be sharing new details later in this presentation. Finally, to be a true leader in rare disease, a critical component for us to realize our aspiration is gene therapy.
As such, we have made significant investments in end-to-end capabilities that facilitate the discovery through buying, building, and partnering, and the development of gene therapies through our global network of study sites, and also to ensure delivery of full commercial supply at launch, which will be achievable through our state-of-the-art internal manufacturing capabilities. We are in an unrivaled position to go to market, both commercially and medically, around the world so we can ensure these breakthrough therapies get into the hands of patients. On this slide, you can see our four therapeutic areas horizontally across the top with a reference to our current in-market products, including VYNDAQEL. Along the left-hand side, you can see the development stages of our various clinical programs, which is where we will focus our presentation today. As you can see, we have a robust pipeline with multiple modalities.
Let me highlight some key numbers for you. We have 10 products total in clinical development, including six new molecular entities in phase III, of which three are gene therapy programs, all of which will have begun dosing by the end of 2020. We also have 10 pre-clinical gene therapy programs. Net-net, we have the potential to launch one new medicine every year for the next five years. Today, we will do a deeper dive into the ones highlighted in red. We will start with rare cardiology. I will now hand it over to my colleague, Brenda Cooperstone.
Thank you, Suneet. Hi, I'm Brenda Cooperstone, the Chief Development Officer for Rare Disease, leading our late-stage development. I'm a pediatric nephrologist by training with more than 20 years of industry experience. Throughout my career, my focus and passion has been in Rare Disease, and recently it became personal for me as well. The picture on the right is of me and my father. Just this past year, my dad, Harvey, was diagnosed with Transthyretin Amyloid Cardiomyopathy, or ATTR-CM, at the vigorous age of 83. It was a long and difficult journey to an official diagnosis, even with a daughter who has worked to develop a drug for this condition for the past seven years. My family is grateful that my father became one of the first patients to be prescribed VYNDAQEL for ATTR-CM, and I'm happy to say that he's doing very well on therapy.
At Pfizer Rare Disease, we are all passionate about bringing medicines to patients like my dad with the potential to transform their lives. As Suneet mentioned, we are growing our leadership in rare cardiology anchored with VYNDAQEL. Our vision is to build a rare cardiac franchise that delivers breakthrough therapies to patients with rare cardiomyopathies, including restrictive, hypertrophic, and dilated cardiomyopathy. We've achieved our first milestone for this vision with tafamidis, ensuring patients globally have access to this life-changing medicine with 34 submissions completed or in progress around the world. PF-07265803, formerly known as ARRY-797, has the potential to be a transformational treatment for patients with a dilated cardiomyopathy caused by an LMNA mutation. Today, I will share with you an update on this investigational therapy and our phase III program, which is currently enrolling.
Additionally, although we will not do a deep dive into this today, I do want to highlight that as part of our overall gene therapy strategy, we have preclinical programs for other genetic rare cardiac disorders. As leaders in Transthyretin cardiomyopathy, we remain committed to this patient community and continue to build our knowledge of this disease and its treatment, as well as develop innovative solutions to facilitate earlier diagnosis of patients with ATTR-CM. First, we have new data that further supports the indicated dose for patients. Given that ATTR-CM is a rare disease with limited numbers of patients available for clinical trial, the pivotal ATTRACT study examined both the 80 mg and 20 mg doses of tafamidis in a pooled analysis versus placebo. The combined 80 mg and 20 mg treatment group showed a dramatic benefit over placebo in both survival and cardiovascular hospitalizations.
The study wasn't powered to show whether 80 mg was definitively better than 20 mg on these important clinical endpoints. We therefore randomized patients from the placebo arm who are coming into the long-term extension study to receive either 20 mg or 80 mg of tafamidis. When these patients were added to the 20 and 80 milligram cohorts from the pivotal trial, we have a robust analysis set of randomized patients with a median of 51 months of follow-up. As you can see on the left panel of this slide, these data confirm that 80 mg of VYNDAQEL, which is equivalent to the 61 mg dose of VYNDAMAX, achieved a 30% reduction in mortality compared to 20 mg. This remains significant across adjustments for age and baseline severity of disease. These results reinforce the importance of appropriate dosing for patients with ATTR-CM to allow for the best outcomes.
A second example is our commitment to better understanding the epidemiology of Transthyretin cardiomyopathy. We are currently proceeding with two large-scale studies, including 3,500 patients, to confirm the prevalence of this rare disease. Finally, clinical trial data has demonstrated that earlier diagnosis and treatment are clearly associated with improved outcomes. We have developed an AI machine learning model using medical claims and EMR data sets that can be launched into healthcare information systems to flag those at risk for wild-type ATTR-CM. We are currently conducting pilot programs with select institutions to further validate its performance and hope to share more later this year upon publication. PF-07265803 is our next opportunity to potentially transform the lives of patients with rare cardiac disease.
This investigational therapy is an oral selective MAPK inhibitor in late phase development for dilated cardiomyopathy related to mutations in the LMNA gene. Patients with this genetic disease present with progressive heart failure, with the majority requiring transplantation or experiencing a major cardiac event by the age of 45. The estimated prevalence is approximately 50,000 in the U.S., but this condition is severely underdiagnosed because genetic screening is currently very limited. Today, there are no treatment options beyond supportive care. p38 MAPK activation is seen in this disease, and treatment with this compound improves survival, cardiac function, and normalized left ventricular morphology in an LMNA mutation mouse model as seen in the lower right of this slide.
The phase II trial of this experimental therapy was a single-arm assessment of change from baseline in six-minute walk distance, which revealed an increase of 69 m over a baseline of 321. This was sustained for the 48-week period of follow-up. Based on these encouraging data, a phase III randomized placebo-controlled trial was initiated with a primary endpoint of six-minute walk distance at 12 weeks and follow-up to 24 weeks to ensure durability of effect. We anticipate top-line results in 2023. We are very excited about the potential of this medicine to bring hope to patients with no treatment today, and we believe that we will be able to leverage our expertise, key learnings, and synergies with tafamidis to ensure its success. We will leave cardiology, and I will transition to my colleague, Seng Cheng, to discuss our focus on gene therapy.
Thank you, Brenda. Good morning, everybody. My name is Seng Cheng, and I'm the Chief Scientific Officer of the Rare Disease Category at Pfizer. I'm a research scientist by training, and I've worked in translational research and gene therapy of rare diseases for over 30 years, during which I had the opportunity to contribute to the advancement of multiple drug candidates into clinical development. Today, I'm pleased to have the opportunity to share with you our efforts at developing what we believe can be a next wave of breakthrough therapies for rare monogenic diseases, particularly in the context of gene therapy. As Suneet mentioned earlier, gene therapy as a therapeutic modality represents an important component of our growth strategy.
Over the past six years, we've made significant investments to build a state-of-the-art end-to-end infrastructure that spans research, development, and commercial to enable the delivery of these transformation therapies to patients worldwide. We are proud of our current late-stage pipeline, with three programs that are expected to gain regulatory approval by 2023, all of which we will discuss in detail today. Additionally, we've developed a pipeline of 10 preclinical initiatives internally that are at various stages of maturity. We've built three state-of-the-art manufacturing facilities with 30,000 sq ft of capacity, which I will also address in this presentation. We are confident that our end-to-end capabilities, combined with our expertise, scale, and geographic footprint, are the key ingredients to successfully ensure that these transformational therapies make it into the hands of patients who need them.
Our most advanced gene therapy programs are for patients with hemophilia B, hemophilia A, and Duchenne muscular dystrophy. Today, I'm happy to share that our gene therapy program in hemophilia B, we now have data from our phase I/II study using fidanacogene elaparvovec, shown as illustrated on this slide, durable expression of factor IX in a 20% of normal range at the four-year time point when administered a dose of 5E11 vector genomes per kilogram. I want to highlight that this represents the longest period of durability data that's been produced by any company to date for a gene therapy for hemophilia B patients. Importantly, the mean annualized bleeding rates and the annualized infusion rates remain significantly reduced in these treated patients.
Given this encouraging safety and efficacy profile, we have initiated a phase III study in 2019, and I'm happy to report that the prospective leading study with 40 patients has now been fully enrolled. Our current plan is to perform an interim analysis and have a pivotal readout with 20 patients and 12 months of ABR in 2021. We are obviously closely monitoring the hemophilia gene therapy development space, which continues to be dynamic to ensure that our clinical plans and timelines meet regulatory expectations. However, given the sustained durability of functional factor level and the ABR rates that we've seen over the four years in the phase I/II study, we believe that fidanacogene elaparvovec has the potential to be best in class for hemophilia B patients. Early this summer, we had reported encouraging safety and efficacy data in patients with hemophilia A who were administered giroctocogene fitelparvovec.
Today, we're sharing an additional four months of expression data in a cohort that have been treated with a dose of three E13 vector genomes a kilogram of this viral vector. As you can see on this slide, we continue to observe expression of factor and activity levels that are sustained at a clinically meaningful levels with a geometric mean of 71% when measured between the weeks of nine and 52. I should note that we also have additional data for a small subset of patients with up to 85 weeks of additional follow-up, showing consistent factor VIII levels as well. Importantly, there have been no bleeds in any of these patients treated in this cohort, and the ABRs of these patients remain at 0.
Should we continue to demonstrate sustained factor levels and reduced ABRs, we believe that this investigational treatment also has the potential to be best in class. We're currently enrolling patients in the six-month leading portion of the phase III study and plan to dose our first patient later this year, which could lead to a pivotal readout of the data in early 2022. Our third clinical program is for boys with Duchenne muscular dystrophy, a program that we've been working on for over four years. In May, we had reported the results from nine boys who were treated at two different doses.
While we observed clear evidence of expression of mini dystrophin, as well as encouraging preliminary signs of efficacy, we had reported the occurrence of three serious adverse events in the six boys who were treated with a high dose, where we saw evidence of complement activation as well as platelet consumption. Today, we're sharing new data from an additional nine boys who were all administered the high dose. We now have a total of 15 boys who were treated with a high dose and 18 boys treated overall. I'm thrilled to share that we have not observed any SAEs using a modified immunomodulatory and monitoring regimen in any of these nine patients. With these boys, we had changed the prophylactic steroid treatment from one milligram per kilogram to an intermediate dose of 2 mg/kg .
I also want to flag that three of the last nine boys were dosed with drug that had been produced using the commercial manufacturing process that had been developed at a facility in Sanford, North Carolina. As a reminder, we had reported expression of mini dystrophin in approximately 50% of muscle fibers and at levels that were sustained at 52% of normal levels at the 12-month time point. Associated with these expression levels were encouraging functional results that included improvement of 7.5 points in the North Star Ambulatory Assessment rating score when compared with an external placebo group, as well as a significant reduction in fat fraction in the thighs of the treated boys. Based on this positive data, we plan to advance this initiative towards a pivotal study start in the next several weeks with a plan to perform an interim analysis of the clinical data in 2022.
Given investments in the manufacturing that I mentioned earlier, we believe we'll be prepared to fully supply the global DMD patient demand for drug following approval. This is particularly important when we engage with non-ambulatory DMD patients who will need higher amounts of the viral vector because of their increased weight. In addition to these three clinical programs, we also have an initiative in Wilson disease, which we are developing in partnership with Vivet Therapeutics. Wilson disease is a chronic, life-threatening disease that's caused by aberrant accumulation of copper in the liver as well as other vital organs. Similar to hemophilia and DMD that I just spoke about, this disease is also caused by a loss of function.
As such, we are applying the same approach of AAV-mediated gene therapy to restore functional levels of the affected protein, which in this case is encoded by the gene referred to as ATP7B. Indeed, as illustrated on the slide, in preclinical studies, we have shown that administration of an AAV vector encoding ATP7B into a mouse model of the Wilson disease led to restoration of copper homeostasis in the liver in a dose-dependent manner. This decrease in copper was widespread, as illustrated in the top panel, showing a uniform decrease in copper levels throughout the liver, which you can see by the change in color from red for high copper levels to green for lower levels when measured using laser ablation inductively coupled with plasma spectrometry. Associated with this decrease in hepatic copper was an increase in fecal copper secretion.
The normal route of disposal of copper is illustrated on the bottom panel. Based on this encouraging preclinical data, we are working to complete the IND-enabling studies and anticipate filing an IND later this year, which could lead to a BLA submission in 2025. We believe that if successful, this would be a first-in-class therapy for this patient population. As you're aware, gene therapy development is a complex task requiring specialized and novel methodologies as well as high levels of expertise. Few companies have complete end-to-end capabilities, expertise, and facilities to support the research, development, and production of these important new medicines, particularly at scale. In this regard, a critical component and key differentiating feature for gene therapy initiatives is our expanding manufacturing footprint.
In anticipation for the need for large amounts of viral vector, we have proactively invested in manufacturing at scale to support rapid drug development and, importantly, urgent and timely access to these medicines. Over the past few years, we made arguably the largest investment, totaling approximately $800 million, to ready three manufacturing facilities. Of particular significance is the ongoing expansion of our plant in North Carolina that will house eight 2,000-liter bioreactors, which when fully operational, will support the production of several thousands of DMD doses per annum. It is our expectation that these facilities will support the production of viral vectors for preclinical and clinical development, and importantly, commercial manufacturing of multiple gene products in parallel by 2022. With that, I will hand this back to Suneet.
Thank you, Seng and Brenda. In addition to updating you on our selected development programs, we also want to share how we are thinking about the go-to-market opportunity. Now I'm going to tie together the information you heard today by sharing insight into our forecasting, which could also be helpful to you for the purposes of modeling. For example, for rare cardiology, in LMNA, we start with prevalence data. We apply other assumptions, which we have simply summarized here and include but are not limited to diagnosis rate, eligibility, access considerations, and competitive landscape. As you can see, we show LMNA side by side with VYNDAQEL to give insight about the commonalities between VYNDAQEL today and what a future dilated cardiomyopathy therapy could be.
For hemophilia gene therapy, we show both A and B together as there is a synergy and consistency in the assumptions, including our beliefs about patients' intent to seek gene therapy treatment. This assumption on motivation is embedded within the eligibility criteria, along with NAb and hepatic impairment. For DMD and Wilson gene therapies, we believe the bolus populations will be drivers of value at launch as existing patients seek treatment quickly, given the lack of available therapies. Beyond that, future value should remain solid for years to come, driven by incident populations for DMD with a meaningful number of boys aging in every year, and Wilson gene therapies as more patients become destabilized over time. We aim high in each of our investigational therapies, and they're being developed to be either first or best in class, and in some cases, we expect they will be both.
We are excited by the trajectory of our business and the potential of our pipeline. In the first half of this year alone, our Rare Disease unit grew 36%, driven by our first big launch, VYNDAQEL. We expect to see even more growth with additional launches in many new countries. VYNDAQEL is just the beginning for Pfizer Rare Disease. You can see here how much substrate we have for the future. Over the next five years, we plan to launch at least one new medicine each year with the aim to make a profound impact on patients' lives. Given our recent success and our robust pipeline, we believe we are poised for significant growth. Our focus, the depth and breadth of our pipeline, our world-leading end-to-end gene therapy platform, and our global footprint position us to continue to be a leading innovator in Rare Disease. Thank you.
We will now turn to Q&A.
Our Rare Disease leadership team is here to answer your questions about the portfolio and the pipeline. Operator, can we please now poll for questions for Rare Disease? Thanks.
Your first question comes from Geoffrey Porges from SVB Leerink.
Thank you very much for taking the question. Just a couple first, you didn't talk much about somatrogon. Just wondering if you could give us a sense of whether that's a meaningful revenue opportunity given the somewhat commoditized market that you're coming into. Secondly, for this business, huge amount of capital that you're investing. Could you give us a sense of whether the profitability and the return on capital for the rare disease business is going to ultimately, or even now, be comparable to the rest of the pharmaceutical portfolio? Should we think about it differently, for example, more like vaccines?
Lastly, just a development question on the Wilson disease program, do you have any sense yet, I know it's early animals, but whether you're seeing a reduction in the copper in the CNS that would result in reduction of the CNS liabilities of that disease in humans? Thanks.
Okay. Well, thank you. I'll start off answering the first two questions, then I'll ask Seng to comment on Wilson specifically. Let me just say we're very excited about somatrogon. We didn't cover it here today simply because we had a lot of, let's say, next wave or next stage opportunities in our pipeline that we really wanted to focus on. That innovation is absolutely on track. It's a big patient innovation, not just convenience going from daily to weekly. It really marks a shift from short-acting to long-acting products. We are on track to file that this year and launch it next year.
I do believe that that is not just a patient innovation in terms of daily dose, but in fact, it's an incremental opportunity for that franchise as we build and maintain scale because there are far fewer competitors in the long-acting market than there are in the short-acting market. In terms of profitability and return on invested capital, if I can say, you can think about this the same as the other innovative units within Pfizer. We abide, as you would have heard yesterday in the executive presentations, by the same criteria for both internal development and for external business development. Seng, if I can turn it over to you for Wilson disease.
Yeah. Thank you, Suneet. That's a good question. We've not had the opportunity to actually measure copper levels in the CNS of the preclinical animals that we tested so far. We are assuming that if we lower the levels of copper in systemic circulation, that's an opportunity for us to actually lower the levels in the CNS as well. That's the aspiration that we have right now with the data that we have in hand. With that, I'll pass it back to you, Suneet.
Okay, thank you. Operator, can we have the next question, please?
Your next question comes from Randall Stanicky from RBC Capital.
Great, thanks. Just a couple on VYNDAQEL, and then another follow-up. With respect to VYNDAQEL, Alnylam's running a phase III studies with an RNA silencing approach. Can you guys talk about how you're thinking about the opportunity for combinations, any supporting data, any hurdles from the payer stance on that? Secondly, I was surprised yesterday, I think was the first time you talked about diagnosis rates for VYNDAQEL looking to come north of 40%. That's above prior rare disease analogs. What's driving that? What caught me is we're in the middle of a pandemic, scintigraphy and patient visits are obviously constrained, and now we're talking about the opportunity for higher diagnosis rates. Thanks.
Okay, great. I'll start off. I'll take the second one first, and then I will ask Brenda to comment on VYNDAQEL in terms of your question on RNAi. Yeah, listen, the diagnosis rates have been steadily increasing over time, and we're pretty pleased with that. You might remember that was one of our key areas of focus when we launched the product. Our treatment rate is also increasing as a percentage of our diagnosis rate. We're very pleased. It's as expected, and that makes us more optimistic for the future, which I think you heard come through before. That's really driven by a concerted effort on our part on the top end to drive diagnosis. We've really been doing a lot of education around our red flag symptoms to educate cardiologists to spot the signs.
Then, yes, scintigraphy has been the pull-through to make sure the diagnosis is confirmed. That's worked out very well. Now, in terms of making sure that people get on treatment, access and affordability has been a key focus of ours, I can say we've also made good progress on that with payers. I think that everyone recognizes the seriousness of this disease and the lack of other available treatments. That has been a favorable recognition, I would say, and that continues to be the case as we go forward. Net-net, a good outcome for VYNDAQEL. Yes, we had previously communicated 30%-50% as the peak diagnosis rate, you would have heard that we're going to go a little bit in the upper part of the range, we'll probably achieve that earlier than we expected. A good outcome.
To your point about COVID, not an impacting factor given the nature of this disease. Brenda, if I could turn it over to you to talk about the other question, please.
Thank you, Suneet. I would say that there is nothing with regard to mechanism that would prevent the combination of tafamidis and RNA silencers. Since tafamidis is the only approved medication currently for ATTR-CM, we do not have any data looking specifically at that. As competitors run through their pivotal clinical trials, there will likely be co-administration, so there may be data available in the future with respect to the efficacy and safety of that combination. Thanks, Suneet. Back to you.
Okay. Thanks, Brenda. Operator, can we have the next question, please?
The next question comes from Terence Flynn from Goldman Sachs.
Hi. Thanks for taking the questions. Maybe just two for me. On your DMD program, any more details you can share about the design of the phase III program and the interim analysis? Maybe remind us what the modified immunomodulatory and monitoring regimen actually entails, and how many patients were treated with Soliris in the phase II study. The second part of the question, you talked about this at the beginning in your prepared remarks, is the acquisition history here in rare diseases where you've built out a pretty broad portfolio. As you think about the forward external opportunities, do you feel like you have more to do here, or are you pretty full at this point in terms of the opportunity set? Thank you.
Okay. Thanks for the question. I'll start off. I'll answer the second question first, and then I'll ask Brenda to comment on both the DMD phase III and the modified regimen that we discussed. The short answer is no, we're not done here. Our focus and our approach, which has been very successful so far, and you would have seen it from the programs we shared, is focused on the four rare therapeutic areas that we talked about. We have three gene therapies in phase III, and we have 10 more in pre-clinical. It's really a result of our build, buy, and partner strategy. When you look through, let's say, the dozen programs that we showed, it's about a third, a third, a third. A 1/3 of them have been internally developed. That's the build. A 1/3 of them are buys, which are sort of more traditional M&A.
About a 1/3 are partnering opportunities where we really collaborate with each. We think we've got more headspace in this area and building out each of our rare TAs, and we're going to continue to use, let's say, both internal development and external BD as a way to accelerate our development. BD is not a strategy unto itself. It's really a means, and one of the means or levers to achieve the goal that we've set for ourselves. Brenda, if I could turn it over to you for the DMD phase III interim and modified regimen question.
Thanks, Suneet. We are very excited about our DMD phase III program, and we understand how important it is to move this forward as quickly as possible for patients and families that are waiting for it. The phase III trial in ambulatory patients is in boys between the ages of four and seven. It's a randomized, placebo-controlled, double-blinded trial. The endpoint of the NSAA is at 12 months. The interim analysis will occur after a portion of patients have received that 12-month data point and will occur in 2022. We will make decisions with regard to disposition of the rest of the study and filing based on the data that is generated. The immunomodulatory changes were specifically increasing the steroid prophylaxis from 1 mg/kg to 2 mg/kg .
No other prophylactic medications were added, and we did increase monitoring, and these are general monitoring diagnostic tests in that critical period of the first two weeks post-dose. With regard to your question on the number of patients treated with Soliris, I'll turn that over to Seng to answer.
Thank you, Brenda. In regard to the amendments that we made recently, we've actually also included guidance on when we might trigger a criteria for use of eculizumab in the event of complement activation with evidence of clinical sequelae. I do want to make the case that with the last line boys that we treated, we've not had the need to use this intervention.
Okay. Thank you, Brenda, and Seng, if I could just say, I think if I could capture Seng's words from his talking points, we are really thrilled about where we are on this DMD program. We've made a lot of progress and especially given what we just discussed, the nine new boys that were diagnosed without any SAEs. Very encouraging and frankly, we're optimistic again about the future here. Operator, please, next question.
Your next question comes from Vamil Divan from Mizuho.
Hi, great. Thanks for taking the question. A couple maybe bigger picture questions on rare disease if I could. Appreciate the comments around how you're thinking about the commercial opportunities for these assets. Can you talk a little bit more on the pricing side? We've seen pretty robust pricing power in rare disease so far. I'm just wondering what your expectation is there going forward, and if there's anything you want to share around sort of innovative thoughts you have around how to adapt our pricing system in the U.S. to accommodate these rare diseases. The second one is just, you mentioned the areas you focus on, things like Wilson, with about a $500 million global market. I'm just trying to get a sense of sort of what size opportunities would you consider meaningful, obviously, Pfizer's a large company.
I think a lot of questions whether these very small targeted rare diseases can move the needle. I'm wondering if your sort of metrics or your thresholds for what's considered meaningful is different in rare diseases than, say, in oncology or other areas. Obviously, the commercial infrastructure here is sometimes less as well. Just trying to get a sense of how you think about opportunities, whether internal or external, that would be meaningful in the future. Thanks.
Let me take both of those, if I could. In terms of Wilson, yeah, you look at the $500 million mark sales. We pulled that out of Evaluate Pharma. I want to be clear, we don't think that that captures the impact of gene therapy. That's based on what current substrate people envision. Obviously, we see that as being a bigger opportunity. You would've seen that we called out Wilson as a $500 million to $1 billion opportunity for us. Right there, our own internal estimates might eclipse what potentially could be as a market size projected or otherwise. We're pretty pleased about where we're going, and obviously that we believe that'll be a first-in-class product, as you would've heard. Look, when it comes to gene therapies, obviously we use the same metrics that all, as I mentioned earlier.
It's really an end-to-end platform where we believe that with the vectors we've chosen, the capacities we've built, the scientific and commercial footprint that we've got, that essentially we can create operational leverage on top of what we're building. In fact, that is something that might be a little bit different than other parts of Pfizer or maybe any other part of another company. That's why we have the multiplicity of the programs that we have. Three gene therapy programs in phase III by the end of this year, and 10 more in pre-clinical. There's a lot for us to benefit from there operationally. Of course, in terms of metrics, we use the same kinds of things that others would use.
In terms of pricing, obviously it would be very early to speculate on pricing, but if I could just give a sense of where we are. We price based on value, okay? That value is based on the profile of the products that we're developing. Those profiles are revealed over time and confirmed, obviously, in phase III. We get to see kind of what comes out of that. Of course, we consider access and affordability to make sure that these would be considered. Now, if I could just add one point. Gene therapy is slightly different than other rare disease products because there's the one-time nature of gene therapies and the changes that that could impact on other chronic treatments that patients might have had that they would no longer need. Okay?
That's maybe an additional variable in gene therapy we might not see in the rest. In all cases, access and affordability remains important. Now, in the U.S., you would've seen with Medicare Part D, we are a long time advocate of reforms, specifically capping out-of-pocket for people on those plans. Frankly, we are also looking internationally at new and creative solutions, such as annuity payments or performance-based payments. I think that you're right in pointing out that there's a certain robustness there, but we're being very thoughtful about how we make sure that those innovative therapies get in the hands of patients, because that's where the impact is actually going to happen. Thank you. Operator, next question, please.
Your next question comes from Louise Chen from Cantor.
Hi. Thanks for taking my questions. First question I had for you is, does the FDA's recommendation for BioMarin to show two years of ABR data close the commercial gap between you and BioMarin, or will you also have to show two-year ABR data? If your hemophilia drug is approved, do you basically think that there's the potential where would it fit into the treatment paradigm, basically, with the potential for another therapy to be approved and lentiviral gene therapy potentially in the future? Last one here is, for hemophilia, what percentage of patients do you think are eligible and would consider a gene therapy treatment? Thank you.
Okay, great. Thank you so much. I'll start off answering the portfolio question you asked. Maybe I'll touch upon the hemophilia numbers. I'll ask Brenda to comment on the FDA and our timing versus the BioMarin CRL. In terms of portfolio, obviously we look at our portfolio in a couple different parts, and you might have seen that we have three different hemophilia products coming to market in the next four years. Two of which are gene therapies and one which is a mAb, the marstacimab. We are obviously playing across the full spectrum, given that rare hematology is one of our key therapeutic areas. We will have products for A, we'll have products for B. We'll have with and without inhibitors. We'll have gene therapies and non-gene therapies.
We think there's a place for all of those, and what we've seen recently in the marketplace is that when a new product comes to market, if it has innovation, that innovation is recognized and has the impact that we think it should have. We're very encouraged by what we've seen, and we see a place for our future innovations in the same way. That's very exciting. In terms of when you look at the second part of your question, which is around hemophilia, and you look at the percentages, we see these markets developing over time, and ultimately we believe gene therapies and non-factor treatments will come to represent 40%-50% of the hemophilia A and B markets.
A might be a little bit on the higher end because they've started that earlier with the non-factors, so maybe closer to 50, and the B would be on the 40, maybe on the lower end. That's kind of where we see those markets coming into play. Specifically around gene therapy, just to be clear, we know that in this category, which is well developed, some patients may or may not choose to elect for gene therapy, and some may also not be eligible. Okay. We believe that that number could be in the 30%-40% range, and we've shown that on our modeling slides in our eligibility, which includes neutralizing antibodies, hepatic impairment, inhibitors, and then we filled in the gap with those sort of intent to seek treatment metrics. You'll see that on the slide there.
Brenda, if I could turn it over to you to talk about the timing and the implications of the BioMarin CRL, please.
Thank you, Suneet. It's our understanding from public commentary that the FDA maintains its same high standards and has not changed the goalpost for approval in gene therapy. We've had robust and collaborative interactions with the agency around our hemophilia A and B programs, and currently there are no planned changes to our ongoing development plan. The hemophilia A program will begin dosing in the next few weeks, and we still anticipate data readout in 2022 as planned. Back to you, Suneet.
Thank you, Brenda. Thank you so much. We're nearly at the end of our Q&A time. Let me just say thank you to everyone for your questions. I think they're very informative, et cetera. I hope you get a sense of our excitement. We're very confident in what we've built here. We are competitive, and we are very focused on what's happening in the market, obviously in the name of patients, et cetera. We've built a lot of capability that we think can really be brought to bear for the benefit of patients and their caregivers. We ultimately aim to have significant growth and impact from what we've built here, and I think you get the sense of that from our prepared remarks and from our Q&A as well. Thank you so much. Let me pass it back over to Chuck.
Great. Thanks, Suneet. Okay, we will now take a 10-minute break, and when we come back, we will pick up with our oncology leadership team. We'll be back in 10. Thanks. Okay, we're back. Before we dive into our oncology program, we'd first like to share a video featuring Scott Wilson, who was diagnosed with metastatic colorectal cancer.
[Presentation]
Now I'd like to turn it over to our oncology leadership team.
Hello, and welcome on behalf of the oncology team. It's people like Scott who motivate us and why we're here today. My name's Andy Schmeltz, and I'm here with Chris Boshoff, our chief development officer, Jeff Settleman, our Head of Oncology R&D, who oversees our research facility in La Jolla, California, and Nick Saccomano, the Chief Scientific Officer at our Boulder, Colorado, research site. Before we dive deeper into our exciting oncology pipeline projects, I'd like to briefly touch on what we've been able to achieve over the past decade. I'm very proud of Pfizer's trajectory from a niche player to a bona fide leader in oncology. The portfolio has delivered unparalleled growth with a 32% five-year revenue CAGR, generating nearly $10 billion in revenue in the last year.
Perhaps most importantly, all six areas of our portfolio are contributing meaningfully to this growth trend, which bodes well for our future. Each area has multiple growth drivers in place, and as you'll soon hear, we anticipate more potential breakthroughs over the years ahead. Bottom line, we're well positioned to sustain growth over the near, medium, and long term. While most of today's presentation will focus on the next wave of potential cancer medicines at Pfizer, I thought it was also important to address our most significant medicine right now, IBRANCE. IBRANCE remains an important growth driver for the company and a critical medicine for breast cancer patients. Since its approval in the U.S. in 2015, over 300,000 patients have been treated with IBRANCE. As a first-in-class medicine, IBRANCE catalyzed the use of CDK inhibitors to treat metastatic breast cancer.
Today, an estimated 66% of first-line metastatic breast cancer patients in the U.S. are prescribed a CDK inhibitor. We see continued opportunities for further class growth moving forward. Despite intense competition, IBRANCE continues to be the CDK leader. Approximately seven out of eight first-line CDK patients are on IBRANCE. As Angela mentioned yesterday, last December, we presented pioneering real-world evidence that showed a compelling 42% overall survival benefit for IBRANCE plus letrozole compared to letrozole alone.
In short, we expect to maintain our leadership position in metastatic breast cancer due to IBRANCE's extensive and sustained positive patient and physician experiences. As you're likely aware, we also have ongoing late-stage clinical trials for potential new indications for IBRANCE on the horizon, including for high risk early breast cancer that's being evaluated in the PENELOPE-B trial, as well as for the PATINA trial in ER positive, HER2 positive breast cancer. Looking at the broader picture, as you can see, the oncology pipeline is not levered to IBRANCE. In fact, our pipeline spans numerous tumor areas. We're advancing a range of targeted therapies as well as medicines that trigger an immune system response to fight cancer, and we expect up to 14 potential approvals by the end of 2025. When I think about these opportunities, a few themes emerge.
First, we're purposely building our leadership in key tumor areas by launching medicines in later lines of therapy or stages of disease, and then quickly investigating these agents in earlier settings where typically more patients are treated for a longer period of time. Second, we have world-class capabilities to deliver therapies that can penetrate the blood-brain barrier, which is a particularly difficult area and represents a significant unmet need for many cancers. Third, we're focusing our science where we are best, where we are pioneers in areas such as ALK and BRAF as well as CDK inhibition. For today's discussion, we'll cover the programs outlined in red. Chris will discuss recent positive data for LORBRENA and BRAFTOVI and walk you through our robust life cycle plans for prostate and bladder cancers.
I'm excited that Jeff and Nick will provide a closer look into our early programs, sharing several new disclosures. With that, I turn the presentation over to Chris to begin our discussion of the pipeline.
Thank you, Andy. Almost a decade ago, we pioneered the first biomarker-driven medicine for ALK-positive non-small cell lung cancer with LORBRENA. Today, we are continuing to make significant advancements for this malignancy with the recent positive top-line results from our phase III CROWN study with LORBRENA in the first-line setting, for which I will share some data today. Up to 40% of patients with ALK-positive non-small cell lung cancer present with brain metastases. LORBRENA is a third-generation ALK inhibitor that we specifically developed to be more potent, to inhibit the most common mutations that may drive resistance to other first- or second-generation ALK inhibitors and to cross the blood-brain barrier. A brain scan is shown from a patient participating in the CROWN study, which is in the first-line setting. This patient had a complete intracranial response, which is ongoing after 24 months on LORBRENA.
The full data set from CROWN will be presented at a future medical meeting where the primary endpoint of PFS compared to crizotinib will be detailed. For the first time, I'm sharing the waterfall plot for a subset of patients presenting with measurable brain metastases. The overall response rate is 82%, with an unprecedented 71% achieving complete response of brain metastases. The Kaplan-Meier curve comparing intracranial progressions on LORBRENA versus XALKORI demonstrates a striking hazard ratio of 0.07. The PFS hazard ratios for the overall population and for those presenting with brain metastases are also compelling. We believe that the CROWN results will position LORBRENA to be highly competitive with second-generation ALK inhibitors in the first-line setting, assuming regulatory approval. We are rapidly advancing our global regulatory submissions for the first-line indication. In the U.S., the application will be reviewed through the FDA's Real-Time Oncology Review Pilot Program.
I will next update you on our targeted medicines, BRAFTOVI and MEKTOVI. We are rapidly expanding our presence in BRAF-driven malignancies. BRAF mutations occur in up to 15% of patients with colon cancer. These represent a particular poor prognostic subgroup, with less than 4% of patients with advanced disease alive at five years. Despite challenges presented by the pandemic, the CRC label expansion from the BEACON data has continued to help drive growth for the BRAFTOVI franchise. Since the CRC launch, the BRAFTOVI combination now comprises 36% of the targeted therapy share of class, and hundreds of new patients have started on this regimen. This is an early look at the phase II data from ANCHOR, which evaluates the combination of BRAFTOVI, MEKTOVI, and cetuximab in first-line BRAF-mutated CRC.
The majority of patients benefited from this combination, with a high objective response rate of 50% and a disease control rate of 85%. We have also seen encouraging duration of treatment for many patients. These data provided a proof of concept to initiate a three-arm phase III study called BREAKWATER that is planned to start later this year in first-line BRAF-mutated CRC. We believe that BRAFTOVI is a best-in-class BRAF inhibitor and with a comprehensive development plan for BRAFTOVI and MEKTOVI that we are rapidly advancing across BRAF-driven cancers. Across the portfolio, we anticipate up to $2 billion of annual revenue contributions in 2027. In addition to the CRC program, we have an ongoing registration enabling study in BRAF lung cancer and phase II studies where BRAFTOVI, MEKTOVI are either combined or sequenced with immunotherapies.
These studies informed a new first-line melanoma trial called STARBOARD, where BRAFTOVI, MEKTOVI are combined with pembrolizumab. Moving now to our franchise of medicines being developed in urogenital cancer, where we are rapidly expanding in prostate and bladder cancer. Urogenital malignancies represent the first and fourth most common cancers in men. Up to 25% of prostate cancers harbor mutations in DNA damage repair or DDR pathway genes, representing potentially a poor prognostic subgroup. For bladder cancer, the majority of patients present with non-muscle invasive bladder cancer. This is an early setting of this disease, before bladder invasion and before systemic spread. These are the latest results from TALAPRO-1, a phase II study of our PARP inhibitor, talazoparib, in heavily pretreated patients with DDR mutated metastatic castration-resistant prostate cancer. At the interim analysis, the objective response rate was 27%.
The response rate in those harboring BRCA1 or two mutations was 42%, with a composite response rate of 72%. Note responses were observed in BRCA1 mutated tumors, potentially differentiating talazoparib from other PARP inhibitors in prostate cancer. These results also give us confidence in TALAPRO-2, our phase III trial exploring XTANDI in combination with talazoparib in metastatic castration-resistant prostate cancer. TALAPRO-2 has now completed enrollment to the all-comer cohort, and the final analysis is expected in 2021. TALAPRO-2 will be the first study to read out for PARP inhibitor in combination with a next-generation androgen receptor inhibitor. This represents a significant opportunity as we anticipate that this investigational combination has the potential to become a new standard of care in this setting if successful. Moving now to bladder cancer.
The waterfall plot is from a phase I study of our subcutaneous anti-PD-1 antibody, sasanlimab, dosed every four weeks or every six weeks in patients with advanced metastatic urothelial carcinoma. In this study, patients were previously treated with at least one prior therapy. These results show activity for sasanlimab comparable to intravenous immune checkpoint blocker data previously reported, and there are ongoing responses in patients coming up to two years on treatment. Earlier this year, we initiated the phase III CREST study combining sasanlimab with BCG or using sasanlimab as a maintenance post BCG induction. There's significant interest in this study from urologists, and we're seeing rapid recruitment to this trial. This is the only global phase III study, including the U.S., in upfront non-muscle invasive bladder cancer. Furthermore, subcutaneous sasanlimab is being developed as a future backbone in various umbrella studies with targeted medicines in our portfolio.
An overview of our GU cancer program shows a robust portfolio of phase III studies spanning early to later stages of the disease. Across the bladder and prostate portfolio alone, we anticipate up to $5 billion of annual revenue contributions in 2027. This includes EMBARK in early non-metastatic castration-sensitive prostate cancer. In summary, we are focused on building our oncology franchises by advancing therapies to earlier lines of therapy. As you can see with the shaded boxes, the majority of our late-stage portfolio is following this strategy. Moving into earlier settings allow us to improve outcomes for larger patient populations, which also correlates to longer durations of treatment. In total, we have 12 ongoing programs that could read out by 2025 with an anticipated $6 billion of incremental revenue contributions in 2027.
I'll now hand it over to Jeff to highlight our next wave of breakthroughs in early development, including our BCMA bispecific, for which we are initiating a registration enabling program.
Thanks, Chris. Chris just described the registration enabling readouts we're anticipating over the next four to five years. Now I'll highlight a few of our earlier stage oncology programs. Here's an overview of our early stage NMEs that are currently in the clinic or are expected to enter the clinic within the next year from our research sites in La Jolla and Boulder. As you can see, there are multiple therapeutic modalities featured in our early pipeline, including small molecule inhibitors, T cell redirecting bispecific antibodies, an inhibitory antibody, an antibody drug conjugate, and a cancer vaccine, targeting cancers in our core indications and more broadly. It's worth noting that there are several potential first-in-class programs listed here that haven't been disclosed previously, and 10 of these NMEs could potentially be approved by 2026.
I'll focus briefly on breast cancer, where there's still a large need for breakthrough medicines that can overcome resistance to CDK inhibitors, including IBRANCE. First, I'll describe our three most advanced next generation CDK inhibitor programs, which enable disruption of each of the critical cell cycle checkpoints. On the left is our CDK2/4/6 inhibitor, which differentiates from our CDK4/6 inhibitor IBRANCE, with the ability to additionally target CDK2. Since CDK2 activation seems to drive IBRANCE resistance in some breast cancers, this molecule has the potential to overcome such resistance, which would be a major advancement for patients. It also has the potential to deliver benefit beyond ER-positive breast cancer, particularly in cancers where CDK2 activation seems to drive tumorigenesis. This molecule is currently in phase I clinical development.
In the middle is our CDK4 selective inhibitor, which has been shown pre-clinically to target CDK4 with more than 10 times the potency of IBRANCE, and without the neutropenia sometimes seen with CDK6 inhibition. That improved TI provides more opportunity for safe combination treatments in other cancer types, and this molecule is expected to be in clinical development later this year. On the right is our CDK2 selective inhibitor, which has been shown in pre-clinical models to combine with IBRANCE to overcome resistance in ER-positive breast cancer and has the potential to drive efficacy in a variety of tumors exhibiting CDK2 activation, especially in combination with standard of care therapies. This molecule is also expected to enter clinical development later this year.
I should add that these novel CDK2 and CDK4 selective molecules resulted from a real tour de force of protein structure-guided medicinal chemistry efforts from Pfizer scientists that yielded candidates with selectivity profiles that many in the industry had predicted would not be possible to achieve. Now I'll describe another exciting oncology program, our HER2 ADC for treatment of breast cancer and other HER2-expressing cancers. This molecule is highly differentiated from other HER2 ADCs, with a very stable, site-specifically conjugated, cell-permeable auristatin payload that yields a molecule with the potential for an improved safety and potency profile. We initiated clinical testing in 2017, and we've seen a very impressive response rate in HER2 positive breast and GI cancers in phase I, including in many patients who had previously been treated with T-DM1.
Notably, we haven't seen any cases of interstitial lung disease to this point, which is expected to enable safer combination treatments and advancement to earlier line treatment settings. We've also seen very encouraging pre-clinical data in HER2 low non-small cell lung cancer tumor models with complete regressions observed in T-DM1 refractory xenografts. When we consider that as many as 40% of non-small cell lung cancers express detectable surface HER2, together with the opportunity in breast cancer, there's the potential for a substantial market for this molecule, and we're now expanding testing in HER2 low breast cancers with plans to expand in HER2 positive lung cancer as well. Lastly, I'd like to highlight a phase I program that we're very excited about, our BCMA-targeted bispecific antibody for the treatment of multiple myeloma.
While there are several approved myeloma drugs, they aren't curative, and there's still a substantial unmet need for these patients. The antibody format we've used is shown on the left. It's worth noting that our antibody has been optimized for binding affinity to both BCMA and CD3, enabling more potent T cell-mediated tumor cell toxicity. We've recently completed dose escalation with more than 50 patients treated. We're expecting to identify a dose this month to support a registrational study start by year-end. Importantly, we've moved from IV delivery to subcutaneous administration. As expected, this has significantly reduced the incidence and grade of cytokine release syndrome, which is a dose-limiting toxicity for T cell redirecting bispecific antibodies and for CAR-T. Sub-Q dosing has the potential for better safety and is also more convenient for patients and physicians.
We're very encouraged by the responses we're seeing so far, including stringent complete responses and responses in several patients who had previously experienced other BCMA-targeted agents. We're now moving aggressively to develop this antibody, both as monotherapy and in combination with other agents. With that, I'll hand it off to Nick for some highlights from the Boulder lab.
Thanks, Jeff. I'm excited to join our forces in Boulder with this great team. These forces are the legacy Array BioPharma team that helped build Loxo Oncology and Mirati Therapeutics. Looking forward, our efforts in Colorado will focus exclusively on the Pfizer pipeline. Boulder's expertise is small molecule drug discovery, and we have a specific track record in drugging the very important RAS, RAF, MEK, ERK signaling pathway, as you saw in Chris Boshoff's portion of the presentation. We have also created two novel dendritic cell-targeted IO therapies. I will touch on one of these today. I'm also going to elaborate on how we're advancing a set of potentially first-in-class tumor agnostic targeted molecules that we anticipate will have differentiated efficacy profiles, and in particular, have the potential to treat or forestall intracranial progression of disease.
Let me start, though, by telling you a little bit more about our potentially first-in-class AXL/MER tyrosine kinase inhibitor, a dendritic cell-targeting IO agent. This molecule has a unique mechanism of anti-tumor immunity that not only enhances the function of dendritic cells, but also protects dendritic cells from the powerful immune-suppressing environment of the tumor. Pre-clinical data support the creation of durable anti-tumor immunity, both as a single agent and in combination with checkpoint inhibition. As such, this compound should combine favorably with sasanlimab and other IO agents. Our initial clinical development plan is focused on lung and gastric cancers, which represent a potential patient population of 70,000-100,000 patients worldwide. We imagine that this mechanism of action could be active across many other solid tumors, including renal cell carcinoma and melanoma. We'll be exploring these additional opportunities in subsequent studies.
The first-in-human phase I clinical trial is now enrolling, and we are aiming to establish proof of mechanism by the end of this year. A potentially important targeted therapy we'd like to highlight today is a molecule that has the potential to become a first-in-class, fully brain-penetrant V600 BRAF inhibitor, which could expand and deepen treatment for patients across multiple BRAF-driven cancers. In melanoma, where we see a significant opportunity, 40%-60% of patients harbor the Class 1 V600 BRAF mutation, and of those, approximately 25% will present with brain metastases at first diagnosis. Pre-clinical studies have shown that our molecule matches the anti-tumor activity of encorafenib in treating systemic disease and demonstrates superior activity in eradicating intracranial tumor implants. We're targeting the end of this month for first-in-human clinical trials. The efficacy of current BRAF inhibitors is limited by poor brain penetrance.
Given this, we believe this molecule, in combination with binimetinib, has the potential, if successful, to represent a significant advance on standard of care regimens in melanoma and other BRAF-driven cancers. Two other examples of our next generation targeted oncology programs take aim at HER2 exon 20 and c-MET exon 14. In both of these cases, the clinical candidate is also engineered to cover the amplified wild type protein, known drug resistance mutants, and to treat or forestall intracranial disease, and as such, together expand the utility of the molecule. Thus, each of these programs addresses a significant patient need. Our HER2-directed molecule targeting amplified breast cancer and exon 20 mutated lung cancer represents approximately 20,045 hundred patients respectively. In non-small cell lung cancer, c-MET exon 14 alterations appear in approximately 10,000-12,000 patients or 3%-4% of lung cancers worldwide.
While c-MET amplification is recognized as a dominant resistance mechanism in patients progressing on targeted EGFR inhibitor therapy. Similar to the BRAF program, both of these are designed to improve upon standard of care given their stellar activity, ability to target resistance, and that they'll treat CNS disease. For both of these programs, we're targeting 2021 for first-in-human clinical studies. I'll now pass back to Andy for some final remarks.
Thanks, Nick. We hope we've given you a clear picture of where we lead the science, how we're prioritizing brain penetrance, and moving our medicines from late stage to earlier settings. We believe there are several potential breakthroughs in our late, middle, and early pipeline. Even with conservative assumptions about diagnosis, treatment rates, and duration of therapy, we can model significant commercial opportunities for several of our key late stage programs, as you can see here. To summarize, we have a strong and growing in-line portfolio with 23 cancer medicines today. We expect to have 24 new molecular entities in the clinic by the end of 2021, and we anticipate up to 14 potential approvals by 2025. We are determined to change the trajectory of cancer for patients like Scott, who are battling this disease every day. Thank you for your time, attention, and interest.
I'll now turn the call over to Chuck to facilitate Q&A.
Thanks, Andy. Our oncology leadership team is here, and we'll be happy to answer your questions about the portfolio and the pipeline. Operator, at this point, can we please poll for questions for oncology?
Your first question comes from Seamus Fernandez from Guggenheim.
Thanks very much for the question. Just a couple here. On the HER2 targeted ADC, can you guys talk about the importance of efficacy versus tolerability? I know with your ADC at ASCO, the data were quite impressive on response rates, but we also saw some neutropenia, and just wondering how that might compare to the kind of efficacy that we see with trastuzumab deruxtecan and the safety issues that we see there, or the lung safety issues that we see there. Separately, can you just help us understand how you think about the size of the HER2 low market opportunity, and the path to development there? Thanks.
Thanks, Seamus, for your questions. I think I'll hand it over to Jeff first to speak to our HER2 ADC program, specifically, on the data, and then I think Chris can chime in in terms of forward development options. Jeff?
Yeah. Thanks for the question. Yeah, let me start by saying we certainly understand that we're not first with a HER2 ADC. We do see some unique attributes of our molecule that we believe give it the potential to be a best-in-class treatment in the right indications. As I mentioned, our ADC was developed using a proprietary linker payload technology and a site-specific conjugation strategy, as well as a very potent cell-permeable cytotoxic payload. That's produced a molecule which so far has shown a very favorable safety and efficacy profile, and importantly, without any signs of interstitial lung disease, which we think could be a real advantage, especially as we move into earlier lines of treatment. We'll need to see how we fare against competitors as we initially expand in HER2 low breast and lung cancer, as I mentioned.
We're being very purposeful about where to pursue further clinical development, but we're prepared to move opportunistically and aggressively as we learn about the strengths and liabilities of the various HER2 ADCs across this landscape.
Thanks, Jeff. Chris, you want to pick up?
Perhaps just to add, you're absolutely correct that the HER2 low is a much bigger space in both breast cancer, but also an opportunity in lung cancer. We are planning to start an expansion cohort specifically in HER2 low, including lung cancer. In the HER2 low breast cancer space, as you know, a lot of those tumors do overlap with hormone receptor positivity. There's an opportunity to combine with either palbo or preferentially for us in the future with one of our next-gen CDK inhibitors, for example, CDK4, which Jeff described.
Thanks, Chris. Maybe just to wrap it together. While we're mindful with our HER2 ADC program, we are not first in class. We're going to leverage that opportunity to use the totality of information available, not only about where we can differentiate with our program, but where there might be gaps in the profile of other programs that are ahead, gaps either in the inherent profile of the molecule, perhaps on the safety side, or gaps in populations where they're not studying. We'll capitalize on that information, to differentiate. Because to be a best-in-class breakthrough HER2 ADC, we're certainly going to need to have a differentiated profile. That's front and center to us. Thanks. Operator, next question, please.
Your next question comes from Andrew Baum from Citi.
Thank you. Couple of questions. Firstly, in light of PALLAS and while noting your real-world data, you do not have a randomized control trial which has shown survival benefit, unlike your competitors. What is your confidence in being able to preserve that market-leading position? It would seem a challenge despite the fact that penetration of the class may go up. Second on the pipeline, two questions. Number one, for your ZYTIGA talazoparib combination, there is a significant co-pay contribution given the Medicare-centric nature of the patient population compared to abiraterone, LYNPARZA. How are you thinking about that? Same vein on your subcutaneous PD-1, again, given fairly substantial Medicare representation, the out-of-pocket contribution is going to be much greater than under Medicare Part B given Medigap. Again, how do you think about that? Many thanks.
Thanks, Andrew, for your questions. I think all three are right up my alley. I'll take a shot first. First, in terms of IBRANCE and kind of our prospects given the intense competition, especially in metastatic breast cancer. IBRANCE is the undisputed leader in metastatic breast cancer. Even over the past year with the accumulation of competitive data, seven out of eight first-line metastatic breast cancer patients are on IBRANCE relative to other CDK. That being said, because it's competitive, one would expect when you start as the only CDK inhibitor and now you're one of three, that share will be challenged over time. Although I must say we've held share very nicely. We do expect growth to come from continued CDK expansion. In the U.S., it's about 66% first-line CDK penetration. In Europe, it's a little bit below 50%, and in Japan, it's around 30%.
We see continued opportunity for CDK penetration that will enable growth. I've got to say that we've had lots of discussions with thought leaders. We've done lots of market research since the PALLAS results have been out, since some of the competitive announcements in early breast cancer have been out. It is clear that oncologists treat early breast cancer very differently patients than they do metastatic breast cancer. We've not seen to date an impact on our metastatic business, and we don't anticipate one going forward based on the strength of IBRANCE's benefit risk profile. The perception of efficacy across all three CDK inhibitors, generally the same. On the safety tolerability side, IBRANCE continues to stand out.
Your second question in terms of really talazoparib, you said ZYTIGA, but I know you meant XTANDI and TALAPRO-2, and then also with our sacituzumab in non-muscle invasive bladder cancer. Clearly, these are going to be not infusions, so not Part B, although I think still to be determined for sasanlimab. We have lots of experience in Pfizer Oncology with oral oncolytics. That's the majority of our portfolio. We understand the considerations around out-of-pocket cost and the importance of patients being able to get the medicine that they are prescribed regardless of their situation. With XTANDI already, lots of experience in an older male population that's Medicare. While we anticipate continued considerations and thoughtfulness that need to be put there, we don't anticipate any downside or concerns.
Obviously, we'll have an opportunity with these medicines to be thoughtful in how we price, certainly with sasanlimab, and in terms of how we contract as well. Thanks for the question. Operator, next question.
The next question comes from Chris Schott from JPMorgan.
Great. Thanks so much for the questions and for all the information today. First on the CDK2/4/6, can you just talk about what type of incremental benefit you're looking at here relative to IBRANCE to move that asset ahead? Does this asset play more of a role in IBRANCE failures? As part of that, can you talk about the selectivity of that asset to CDK2 versus CDK4 and CDK6? The second question, just coming back to IBRANCE and the metastatic breast cancer market. Certainly hear your argument in terms of IBRANCE remaining a leader in that setting. Can you just elaborate a little bit more just on the size of that market? I think you've talked in the past about you expect that there could be some CDK retreatment, post adjuvant therapy.
Just talk a little bit, is that something you expect that we need to see more data for that to occur? Can we think about maybe some of these markets contracting a bit as adjuvant comes on the market and maybe slows the progression of some of those patients to metastatic? Thanks so much.
Thanks, Chris, for your questions. Jeff, I'll hand it to you on the CDK2/4/6 program. Chris, maybe you can speak to some of the clinical trials that are underway in terms of CDK and some early breast cancer and subsequently CDK-based regimens in metastatic breast cancer as well. Jeff?
Sure. Yeah, thanks for the question. First, just to reinforce a point, Andy, that you made, it's worth noting that Pfizer has been leading the way in the CDK space. By doubling down in this area with our next generation CDK inhibitors, we now have really three different kinds of opportunities to further improve on IBRANCE and to expand the utility of cell cycle inhibition to tumor types beyond ER-positive breast cancer. Your question was focused on CDK2/4/6. With that program, where we're close to identifying a safe phase II dose, we'll be exploring its ability to overcome resistance to IBRANCE in the setting of combination treatment with endocrine therapy. Whereas I mentioned accumulating evidence implicates CDK2, you had asked about how hard we're hitting CDK2 versus CDK4 and CDK6 when we compare to IBRANCE.
We're pretty potent and almost equal potent on all three, CDK2, CDK4, and CDK6 with this molecule. We're optimistic about its profile in terms of target coverage. We anticipate a pivotal start for that combination potentially in 2022. Now, as I described, we expect to be in the clinic in the next few months with our CDK2 and CDK4 selective programs, which you asked about as well. With our CDK4 selective inhibitor, we anticipate being able to cover that really important cell cycle regulator with unprecedented potency and without the neutropenia that we can sometimes see with IBRANCE. When we consider the critical role of CDK4 in cell cycle checkpoint control in cancer cells from breast and other tissues, we see several additional opportunities for this molecule.
Depending on what we experience in terms of safety and efficacy, the CDK4 inhibitor could potentially be combined with our CDK2 selective inhibitor, or in other indications, it could be combined with other targeted agents, as well as IO agents, where our preclinical data support a rationale. With our CDK2 selective inhibitor, there are three different kinds of ways it could deliver value. As I just mentioned, it could be combined with our CDK4 selective inhibitor to cover both CDK2 and CDK4 while avoiding CDK6-mediated neutropenia. It could also be combined with IBRANCE to overcome CDK2-driven resistance. It could also be used in tumors that are CDK2-driven primarily, such as those that have lost RB or those with increased cyclin E, which is seen, for example, in many ovarian and triple-negative breast cancers.
Because neither of these two selective inhibitors is expected to cause significant neutropenia, we also expect them to be combined safely with other agents, including cytotoxic chemotherapies that can cause neutropenia. We see a variety of development opportunities in indications in both breast cancer and beyond, where CDK activation seems to be playing an important role. Chris, do you want to add to that?
Yes. I think just to state in endocrine or hormone receptor-positive breast cancer, we really see the cell cycle as foundational because the estrogen receptor and the progesterone receptor pathways work by way of the cell cycle. Blocking CDK4/6, we see it as a foundational therapy that should be used in different lines. We already have some evidence for palbo after palbo, but there's ongoing at least six studies that we're aware of testing a CDK4/6 after CDK4/6. We suspect it's going to be just like endocrine therapy that's used after endocrine therapy. Also from a phase II study, one of our in-house PI3K inhibitors, which we combined with palbociclib, post-palbociclib, we did see significant responses. We also have to remember in terms of adjuvant versus metastatic treatment, there's often a difference in the time of progression.
For tumors that progress during adjuvant treatment or within six months of adjuvant treatment, that's very different from a cancer or malignancy that progressed six or 12 months post stopping adjuvant therapy. In this case, in hormone receptor-positive breast cancer, the majority of tumors will progress much later. I suspect there will not be any erosion into using a CDK4/6 in first-line metastatic setting, post-use in the adjuvant setting.
Thanks, Jeff and Chris. Operator, another question, please.
Your next question comes from Steve Scala from Cowen.
Thank you. I have a few. First, now that you have seen the full PALLAS data, perhaps stratified by risk, are you more or less confident in the outcome of PENELOPE-B? The second question is, what do you think about the prospects for success of immune oncology in prostate cancer generally? Then third is, what is Pfizer's interest in KRAS, and specifically combination of KRAS with CDK4/6 and BRAF MEK? Thank you.
Thanks, Steve. Good questions. PALLAS and PENELOPE prospects, IO in prostate cancer, KRAS and KRAS combinations. Chris, maybe to you for the first two. You can comment on KRAS. Nick probably will take that one.
Okay. Thank you. Very good question. Obviously, we were very disappointed in the result of PALLAS. A reminder that Pfizer is not the sponsor. This study was conducted by external sponsors. We are working very closely with them to understand the sub-analysis better, to understand the subgroup analysis better, and some of those data will be presented later this week at ESMO, when monarchE will also be presented. Just a reminder that between monarchE, NATALEE, PENELOPE, and PALLAS, the baseline patient characteristics, the inclusion criteria, and the trial designs are very different. It's going to be very difficult to just compare between the different studies. Very different studies. PENELOPE-B will read out, as you know, later this year in Q4. It's designed specifically for the highest-risk population.
It's a subgroup of the Stage 2 and Stage 3 disease population, specifically those patients with residual disease after new adjuvant chemotherapy with a high clinico-pathological stage. CPS scoring is a standard scoring used by oncologists and pathologists for risk stratification. It's the high-risk group specifically. We are looking forward to the readout later this year. In terms of prostate cancer, we do have, I think the next question was on prostate immunotherapy. There's two ongoing studies that we are collaborating with Merck, and Merck are conducting these studies with pembrolizumab in combination with XTANDI, enzalutamide. One study is in metastatic castration-resistant prostate cancer, and one is in metastatic castration-sensitive prostate cancer. These are ongoing studies. They haven't read out yet.
I think in general, we think of prostate cancer, certainly like you, as a tumor that's more cold, low tumor mutational burden, and also low in PD-L1. Certainly a higher bar in prostate cancer. We do have a program, though, that's ongoing in terms of bispecifics that we're developing in early development. That could potentially be T-cell redirected therapy is potential one way to get T-cells into prostate cancer and have activity there. I don't know if you want to add anything to prostate cancer and the immune landscape, Jeff, and then over to Nick.
No. I think you covered it well, Chris.
Nick? KRAS.
Okay, Nick, KRAS question.
I'm picking up on KRAS. We're clearly aware of the attributes of the Mirati compound as well as the other competitors, as well as the preclinical data supporting beneficial combination with CDK inhibitors as well. I know the Boulder site was very involved in drugging GTPases over the last several years, and we clearly maintain an interest in this area as well. I think you should look to some of those who are in the clinic right now to capitalize on the preclinical data in configuring studies in combination.
Thanks, Nick. Operator, I think we have time for one more question.
The next question comes from Umer Raffat from Evercore.
Hi. Thanks so much for taking my question. I had a couple, if I may. First, I noticed on your slide deck yesterday that PENELOPE readout timing is now indicated for 2021, and it was previously expected second half 2020, broadly speaking. I just wanted to understand what drove that. Is there any possibility that the PENELOPE data, which is in higher-risk patients, CPS, EG 3 plus, could be combined with a higher risk subgroup of PALLAS to form the basis of some sort of adjuvant indication for IBRANCE? Does that possibility exist? That'd be really helpful.
Thanks, Umar. Chris, to you for these.
Okay. Uma, as you know, PENELOPE is obviously like all these studies of event-based . We are now confident that the readout will occur in Q4 2020. It's not 2021, Q4 2020. We have to wait for the result. If PENELOPE, as we hope, is a positive study, we'll have to look at that opportunity and whether there's an opportunity to use some of the data from PALLAS. I don't want to speculate about that yet until we have a positive study or positive readout for PENELOPE-B.
Thanks, Chris. Well, looks like we're just about out of time. On behalf of the four of us, I want to thank you for your questions. We're very excited about our future prospects in oncology, and we look forward to bringing breakthroughs, to help serve cancer patients. Chuck, back to you.
We'll now have a short break, five minutes, and then we'll return to hear from three of our leaders regarding our COVID-19 antiviral and vaccine program. We'll be back in five minutes. Okay, we're back. We'll move into the COVID program. I just want to make one quick comment just so there's no confusion. The question on the PENELOPE-B study readout in 2021. What Mikael Dolsten's slide showed yesterday was a potential launch in 2021 for that potential indication. The readout, as Chris and Andy still reiterated, is still expected in the fourth quarter of this year. Before we jump into our COVID-19 program, we'd first like to share a video. Roll the video, please.
[Presentation]
[Presentation]
[Presentation]
[Presentation]
[Presentation]
[Presentation]
[Presentation]
[Presentation]
Now I'd like to welcome back live Mikael Dolsten, our Chief Scientific Officer and President, Worldwide Research, Development and Medical, Angela Hwang, Group President, Biopharmaceuticals Group, and Kathrin Jansen, Senior Vice President and Head of Vaccines R&D. I'll now turn it over to Mikael to start the COVID presentation.
Thank you, Chuck. Today, we will focus on Pfizer's robust response to COVID-19, discussing the development of a potential mRNA vaccine and our efforts advancing a potential novel antiviral. I want to talk first about our potential first-in-class antiviral. As COVID-19 began to emerge, we screened some of the compounds from our legacy SARS protease lead collection for activity against SARS-CoV-2 3CL main protease and against other coronaviruses. From the compound screened, we identified.
Mike, I can talk to you.
PF-07321332 as a potential drug candidate. On the top left, we can see the effect of PF-07321332 against two key lineages of SARS-CoV-2, the one that originally emerged in the pandemic in yellow and a strain that emerged later in the pandemic in blue. As you can see from the table on the bottom left, our compound has strong antiviral activity against both SARS-CoV-2 lineages in a human lung carcinoma cell line. On the right-hand side of the slide, you can note that our drug candidate displayed potent activity against a series of different coronaviruses. This suggests that we have a pan-coronavirus protease inhibitor, as it is effective in vitro against many existing coronaviruses, and thus may possibly also be active against new coronaviruses. In the next chart, you can see lower numbers reflect better potency. The PF-07321332 drug candidate displays 100-fold selectivity for coronavirus 3CL proteases over human proteases.
We have in vivo antiviral studies ongoing with academic labs, and we are encouraged by the interim results we are seeing. Given that remdesivir and our compound have distinct antiviral mechanism of action and antiviral treatments have historically benefited from combination therapy, we explore the antiviral in vitro activity of this combination. The figure shows different concentrations level of remdesivir, represented by different line colors in a dose response with our 00231 drug candidate. Our compound has a potent single agent EC90 in this SARS-CoV-2 antiviral assay, a level where there is precedence for clinical efficacy with viral protease inhibitors. We recorded that there was a two to threefold more potent EC90 value with both agents combined. These in vitro data suggest that you may be able to get the same control of the virus with lower concentration of each compound when used in combination.
Collectively, this in vitro data suggests our compound has the potential to be effective as a single and combination agents against SARS-CoV-2. To develop 2C1 into a drug candidate for intravenous infusion, we prepared a phosphate prodrug, which has high solubility. The prodrug candidate is efficiently converted in in vivo models to the active 2C1 drug candidate. Intravenous fusion of the prodrug candidate is expected to leave a high concentration of active compound to efficiently inhibit the viral protease. Well tolerated and safe in rodent preclinical safety thus far, which has supported IND filing, is being further studied in ongoing multi-dose GLP rodent and non-rodent studies for up to four days. Collectively, the preclinical data suggests that we should be able to test several multiples of the antiviral EC90 clinical trials.
We believe this potential first-in-class protease inhibitor may give us the best opportunity to show meaningful antiviral activity to help treat COVID-19 patients. We initiated a phase I-B study early in September and recently began dosing. We are planning a pivotal phase II/III study starting late 2020 or early 2021, with a projected approval in the second half of 2021. Moving on to our mRNA COVID-19 vaccine candidate in collaboration with BioNTech. The mRNA platform is well suited for a pandemic response on many levels. First, safety. Unlike some conventional vaccines, mRNA vaccines are non-infectious, and there is no need for virus to deliver the mRNA vaccine. These are potential favorable safety properties. Second, mRNA vaccines pose minimal risk of anti-vector neutralizing antibody response, thereby permitting repeated boosting, which may be important if additional vaccinations are needed to control the virus in the future. Third, speed.
mRNA technology enables rapid development if the vaccine is to quickly adapt to potential mutation of SARS-CoV-2. mRNA vaccines have an efficient path production process without the need for complex mammalian cell systems. Let's discuss more about the design feature of our COVID-19 lipid nanoparticle. In the middle, we see the depiction of a lipid nanoparticle based on prior EM data and informed by our hypothesis on how we expect lipids and RNA to behave. The lipid nanoparticle, or short LNP, has two components, the encapsulated mRNA and the lipids. On the left is the encapsulated modified mRNA, which is codon-optimized and encodes the viral spike protein. Our encapsulated mRNA vaccine candidate elicited a broad immune response in the phase I/II trial, and we have seen mostly mild to moderate vaccine reaction in our trials to date.
Let's look at the lipids, which together with the RNA form chemically defined lipid nanoparticles with no ability to infect or spread. The lipid nanoparticles do not include foreign viral proteins or vector protein without immune potential. In our phase I/II trials, LNP-formulated vaccines candidates have elicited robust antibody CD4 and CD8 T cell response against the virus at low doses with favorable tolerability. I want to share our thinking on the long-term opportunity to expand on the mRNA platform across three possible waves. We are in the first wave with a BNT162b2 COVID-19 vaccine candidate that has the cutting-edge design of a lipid nanoparticle and modified mRNA. We are currently working on wave two, which we anticipate in 2021 to have a defined lyophilized formulation candidate that would be stored at refrigerator temperature.
We will also explore new mRNA technology with a potentially lower dose and augmented immune response. These innovations could help us deliver next generation SARS-CoV-2 vaccine, potentially suitable for different variants of SARS-CoV-2. In wave three, possibly around 2022, we see the emergence of a potential self-amplifying multivalent flu mRNA vaccine. This may substantially improve flu vaccine efficacy. We see the opportunity to extend the use of this technology beyond flu and into other infectious diseases. It's my pleasure to turn it over to Kathrin.
Thank you, Mikael. It is a pleasure to speak with everyone. My name is Kathrin Jansen. I'm Senior Vice President and Head of Vaccine Research and Development at Pfizer. Today, I will share data with you on our quest to develop a COVID-19 RNA vaccine with our partner, BioNTech, to curb this devastating global pandemic. To briefly orient you again to our program, unlike other companies, we have made a conscious decision to evaluate multiple RNA-based candidates to position ourselves and select the one with the best safety and tolerability profile. From day one, we knew that the selection would be data-driven with an emphasis on clinical data.
Based on the totality of data obtained at the end of July, we announced that our BNT162b2 candidate or b2, as we call it, based on a modified RNA platform expressing the full spike protein and at the 30 mcg dose level, would advance in our phase III efficacy studies using a two-dose regimen. Why did we choose b2? We chose the b2 vaccine candidate because our early work showed beneficial protective effects in a primate SARS-CoV-2 challenge model, a safe tolerability profile in younger and older adults, a robust SARS-CoV-2 neutralizing antibody response across all ages, and strong CD4 and CD8 T cell responses. First, I'm excited to share our preclinical challenge data that are now available on a preprint server. Six rhesus macaques were immunized with two doses of our b2 clinical candidate.
The immunized rhesus and three unimmunized controls were challenged with one million live SARS-CoV-2 virus units, split equally between the trachea and nose. As you can see in the control rhesus in the gray bars, viral RNA was detected in the bronchoalveolar lavage or BAL, indicating infection in the controls. In b2 immunized rhesus, shown in the teal bars, infection was completely prevented in the bronchoalveolar lavage of the lung, while RNA positivity was still observed on day six in the control group. The difference in viral RNA detection in BAL between b2 immunized and control rhesus macaques after challenge is highly statistically significant. Here, I share with you the clinical safety and tolerability profile from our phase I U.S. clinical study that evaluated multiple b2 dose levels.
Shown on this graph are post-dose one tolerability data after administration of 30 mg of the b2 candidate in 12 subjects, 18 to 55 years of age, and 12 subjects, 65 to 85 years of age. Also shown are the nine subjects in each age group that received placebo. We see a mostly mild and moderate tolerability profile. On this graph, we see the post-dose two data. As expected, we saw a somewhat higher systemic event rate after dose two. The 30 microgram b2 candidate continued to be well-tolerated in both young adults on the top and older adults, bottom, with only mild to moderate events and low incidence of fever and chills in older adults. There were no Grade 4 events where efficacy is reported. In general, tolerability was similar to the rates we see in some licensed vaccines.
I'm delighted to share with you now our clinical SARS-CoV-2 neutralizing antibody responses. Note that the data were generated in a real virus neutralization assay. The vaccine candidate at the 30 microgram dose level elicited modest neutralizing antibody responses after a single dose that were boosted to higher and very robust levels after a second vaccine dose, shown here for day 28 and 35 in young and older adults. We were pleased to see that neutralizing titers in older adults, the right panel, while somewhat lower than the younger adults, still increased between day 28 and day 35. For 18 to 55-year-old participants, only 11 serum specimens were available per protocol on day 28, and only 10 were available on day 35, which makes an interpretation of the day 28 to day 35 responses difficult in this cohort.
Note, however, the generally very tight neutralizing antibody responses in young and older adults compared to naturally infected individuals in the HCS panel . For all post-dose two time points, neutralizing titers in immunized individuals were higher than those in the convalescent serum panel. As Mikael mentioned, the ability of RNA vaccines to boost without the vulnerability of anti-vector immunity is a strong plus for the RNA platform should we see the need to give more frequent boosters. Now I'm pleased to share with you an example of the T cell responses we see with our vaccine candidate b2. Why are T cells important? We are learning now that people can contract COVID-19 more than once, and antibody levels to prevent infection may wane over time. CD4 and CD8 T cells are first responders and help our adaptive immune system.
CD8 T cells particularly are important to identify and destroy virally infected cells to contribute to prevent disease. Shown here are representative T cell data from a single trial participant who received 10 mcg of b2 to exemplify the T cell response. On the left, note the CD4 T cell response elicited by b2 that is comparable to recall responses to common pathogens at the CEF well. Very importantly, note the strong CD8 T cell response on the right elicited by b2. As with the CD4 responses, we see higher overall T cell responses to the full spike protein, that's S1 and S2 peptide pools combined, than to the small RBD domain. These responses are as strong as recall responses to pathogens such as influenza and CMV. Additional T cell responses elicited by b2 will be provided in the scientific manuscript in the near future.
This strong CD8 response was another important selection criterion for B2, we believe differentiates our B2 vaccine candidate from some other late-stage clinical development programs. Based on the totality of data that I just described to you, we decided to advance B2 at the 30 mcg dose level into our phase III efficacy study. As a reminder, phase III is a one-to-one vaccine to placebo randomized observer blinded study to collect safety and efficacy data needed for future licensure. It is an event-driven trial. The primary endpoints are the prevention of COVID-19 in those who have not been infected by SARS-CoV-2 before immunization, prevention of COVID-19 regardless of whether participants had previously been infected with SARS-CoV-2. We are also exploring protection against asymptomatic disease.
Enrollment in the study has progressed very well, with close to 30,000 subjects enrolled in three countries, and sites planned in an additional three countries. As of yesterday morning, over 12,000 subjects have received a second dose. We are also very proud of the diversity in our study population, as shown here, reflective of populations that are in particular need of a vaccine. I'm pleased to announce that we plan to increase enrollment in our phase III trial to approximately 44,000 participants. This allows us to further increase the trial population diversity and include adolescents as young as 16 years of age and individuals with chronic stable HIV, Hepatitis B, or Hepatitis C, as well as provide us with additional safety and efficacy data. What about our timeline? The pivotal trial is event-based, and there are many variables that will ultimately impact timing.
As stated previously, based on current infection rates and our assumptions, we continue to expect that a conclusive efficacy readout is likely by the end of October. It is clear from FDA's June 30th guidance on COVID-19 vaccine development that the agency is continuing to apply its high standards for an EUA and BLA, an approach that we support. A rigorous approach to the development of a safe and efficacious COVID-19 vaccine is critical to help fight this pandemic. Our trial design allows for interim analyses and unblinded reviews by an independent external data monitoring committee for ongoing data and safety monitoring. We are in the process of preparing our regulatory packages and providing information on an ongoing basis to regulators.
In order to preserve the integrity of the study, we will provide information about interim analysis on numbers of events only if and when the DMC notifies us that there's a conclusive readout of efficacy or futility. Given the importance of safety, I wanted to share a few words about safety evaluation in our trial. As for all our vaccine studies, we utilize rigorous and continuous safety monitoring. Safety monitoring is performed by blinded Pfizer qualified personnel and by an independent external safety monitoring committee composed of vaccine and safety experts that reviews unblinded safety data on a weekly basis. As expected with a trial of this size, SAEs have been reported to regulatory agencies as well as to the DMC, which has access to unblinded data. The DMC has not raised any concerns to date, and we continue to recruit and enroll as planned.
Lastly, I would like to share with you blinded emerging tolerability data from our phase III study with a data cutoff of August 27th. This first graph shows post-dose one data from over 5,000 18 to 64-year-olds and nearly 2,000 65 to 85-year-olds. When you look at this data, it is important to understand two things. First, since these are pooled blinded data, about 50% of subjects have received BNT162 and about 50% of subjects have received placebo. We are collecting the tolerability data only from a subset of the trial participants up to around 6,000 in the U.S. and then around 500 subjects from each country participating in the study. This is designed to give us a reliable impression of the frequency of local and systemic reactions.
That is why the number of participants reflected is fewer in number than the nearly 30,000 enrolled that I mentioned earlier. Note the mostly mild and moderate tolerability profile. This second graph shows phase III post-dose two data also blinded in over 1,200 participants, 18 to 64, and nearly 500 participants aged 65 to 85. We are pleased that this blinded tolerability data from our phase III study after both dose one and dose two show a mostly mild to moderate overall tolerability, consistent with what was observed in phase I studies. We see this data only on a blinded basis, so we do not know if the subjects experiencing the event have received vaccine or placebo. The DMC has access to unblinded data, so they would notify us if they have any safety concerns and have not done so to date.
With that, I'd like to hand over to Angela. Thank you.
Thank you, Kathrin. Well, you've heard about the exciting R&D activities behind our potential COVID vaccine program from Mikael and Kathrin. Let me take you through our commercialization plans now. What differentiates the Pfizer-BioNTech collaboration is that our vaccine capabilities are end-to-end and all in-house. Our clinical capabilities are a strength. It is not easy to conduct a 30,000-patient vaccine study, but we've done this before. We successfully ran an 80,000-patient vaccine efficacy trial, the CAPiTA study for Prevnar 13 in adults. Pfizer has had a strong track record on vaccine development and commercial distribution that has led to the successful registration and launch of multiple vaccines over the years. For our potential COVID vaccine, I see a pandemic phase first that could last till the end of 2021 into 2022, where we will need high volumes of doses to be provided to governments for large-scale vaccinations.
For this pandemic period, we're pricing the vaccine for broad access rather than using the typical value-based pricing frameworks and supplying it mainly through government contracts. We expect to supply up to 100 million doses globally in 2020, 1.3 billion doses in 2021, and we expect to have agreements covering all of these doses. To date, we have already gained commitments for over 450 million doses with options for 600 million more. We're in active negotiations over term sheets with 22 countries right now, and we're in various stages of discussions with 30 more countries, including the COVAX facility, where we have issued an expression of interest.
The COVAX facility is a mechanism established by Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations, as well as the World Health Organization that aims to provide governments, including those in the emerging markets, with early access to a large portfolio of COVID-19 vaccine candidates. The in-country dose allocation will then be on the stability of the health authorities of each country, and we will work with them to provide input. We also know how important it will be to increase the public's confidence in vaccines. We're activating multiple channels, including DTC, to educate the public on the importance of vaccinations as well as providing education around the safety standards of the COVID vaccine.
Pfizer is also supporting industry education campaigns such as the Stronger Campaign launched by BIO, which aims to build a movement of pro-vaccine supporters and to counter the vaccine misinformation that you see online. Our global supply team has worked so hard to develop a practical and reliable large-scale cold chain logistics plan built off the supply chain plan that we're using for our phase III trials currently. We believe governments will be able to effectively dose patients. Our distribution centers will be equipped with ultra-low temperature storage capabilities. The vaccines will be shipped directly to vaccination centers in a thermal shipper that can maintain the ultra-low temperatures. These shippers can hold anywhere between 200 and 1,000 vials. Each thermal shipper also contains a reusable GPS-enabled temperature monitoring device to ensure that the vaccines are maintained within required temperatures.
At the point of use, there are going to be three options for storage. One, the ultra-temperature freezers are commercially available now, and the freezer can extend shelf life for up to six months. Alternatively, the thermal shipper can be used by recharging it with dry ice. This can provide 15 days of storage. The vaccine can be stored for five days at refrigerated two to eight degree conditions. We're continuing our stability studies to generate additional data. Given the pandemic, though, we don't expect that the doses will be stored for long. On the contrary, we anticipate doses will be administered shortly after they are received at the site. To prepare the vaccine for administration, each vial will be diluted with saline, and this will enable five doses per vial. The diluted vial is stable at room temperature for six hours.
Remember, the vaccine distribution, storage, and administration processes that we just described are routinely and effectively done now as part of our clinical trials, and it works. This is why we're confident about our ability to distribute these doses and for the vaccine to be stored appropriately until administration. Let's shift to the potential vaccination scenarios that we're preparing for. The durability of the vaccine efficacy will inform what vaccinations will look like in the pandemic and post-pandemic phases. If immunity is short-lived, you may expect annual vaccinations to take place. If immunity is prolonged, there's potential for a scenario where you have to boost after several years, much like tetanus today. If immunity is very prolonged, we may not need boosting, similar to what you see in some childhood vaccinations today that are given just once, like hep B, measles.
However, the possibility of the virus changing exists, and/or the emergence of other closely related viruses is possible. Therefore, the need to make will always be present. We specifically chose to collaborate with BioNTech because of the unique benefits of the mRNA technology and the advantages that this would offer to cover the entire range of vaccination possibilities. The three key advantages to the mRNA technology are as follows: The ability to quickly modify and to develop a new vaccine if the virus strain changes, the ability to boost if we need, and the ability to also elicit both B cell, which is the antibody, as well as T cell immunity. The good news is this technology will allow our vaccine to have a role in any potential post-pandemic scenario. This is why we will have a sustainable business. Thank you.
Now I'll hand it back over to you, Chuck, for Q&A.
Great. Thanks, Angela. What we'll do now is we will bring Albert in, and we'll have a Q&A session with Albert, Angela, Mikael, and Kathrin, so we can address COVID questions or any questions from the presentations yesterday by Albert, Angela, and Mikael. I'll now turn it over to Albert to kick off the Q&A session here. Operator, if we can poll for questions.
To ask a question, please press star one on your telephone keypad. To withdraw your question, press the pound key. Your first question comes from Vamil Divan from Mizuho.
Great. Thanks so much for taking the question. Thanks also for all the info and all the work you're doing on the COVID-19 side. Maybe one question for Albert, more general from yesterday's presentation and one on COVID-19. Albert, the question we received from some investors just around you mentioned the current pipeline you see replacing all the revenues that are going to be lost from the upcoming LOEs. The question is, we know those revenues will be going away in the second half of the decade and the pace at which you think those can be replaced.
If you think about the second half of the decade, are you comfortable giving any sort of sense on this, or annual basis or over the five years, will there be a sharp decline in revenues and then we see a strong recovery as the pipeline sort of matures and plays out over time? Or do you think potentially we may not see any decline in revenues at all as we go in 2026, 2027, 2028? Then my question on the COVID vaccine, I know you're not going to speak much in terms of timing around interims and things like that.
I'm just wondering if you can comment at all in terms of the DMC and what they're looking at in terms of especially the follow-up or how much duration of response will they have as they're sort of making their decisions around a conclusive efficacy for the vaccine. Obviously, people are wondering what the long-term efficacy is here, maybe if you could comment on there would be helpful. Thanks so much.
Yeah. Thank you, Vamil. We do feel confident that the post 2026, our pipeline will at least replace, which means that we do feel comfortable that we will be at not decline, we'll be at growth. Our ambition is to have sustainable growth. Our ambition, it is to move it to almost 6%.
This is what we strive to do. That will come from the pipeline, also from additional enhancements of the pipeline, three assets, so that they will be able to replace this streamline of the growth.
Happy to do that. We have a DMC with renowned experts. They review on a weekly basis serious adverse events and any adverse events, and on an unblinded fashion. In addition, of course, Pfizer's expert review on a blinded basis. At certain case counts, I think we have revealed that the first one would be 32 cases. They will review efficacy distribution between the vaccine groups, followed by several other interim analysis that may allow them to stop the study because of efficacy, continue the study, or declare futility. So far, there has been no safety signal reported. You have seen also from Kathrin, blinded data on tolerability and reactogenicity, which confirms the mild to moderate favorable profile in the phase I, II.
Thank you, Michael. May we go to another question.
Your next question comes from Navin Jacob from UBS.
Hi. Thank you so much for taking the question. A couple, if I may. Number one, I think you had suggested that the enrollment in the phase III was in part due to a desire to enroll a more diverse set of subpopulations, which is understandable. Also, I believe I missed, please correct me if I'm wrong, but there seems to be perhaps a slowing of also the event rate or in slowing of infections. If that's true, is that also part of why there was an increase in the trial size? Then with regards to the elderly cohort, and the neutralizing antibodies increasing through day 35, certainly encouraging. When we cut the data for the convalescent plasma patients, the neutralizing antibody titers that is, for patients above 55 years old, the NT50 was 142 versus the roughly 200.
Apologies, I'm just seeing that data very quickly. You put up about 200 or so, which is about maybe one and a half times convalescent plasma for the patients that were above 55. Is that level of fold enough in your mind to provide enough of an event reduction in those patients that are most at risk, i.e., the patients that are over 55 years old? My last question is, how are you thinking about durability of efficacy? What gives you confidence about how long the efficacy could last for? Thank you so much.
Yes. As we said already, the increase of the number on the subject in the enrollment is coming mainly from the fact that we have already 30,000 people. We feel much more comfortable with the safety profile of the vaccine. We are going to much more vulnerable populations, 16 years old, for example. People that they have HIV or Hepatitis C or Hepatitis B. The events indeed in the U.S. are slowed down. Just to make clear, though, that we are taking this current slow event when we speak about we expect the conclusive result by the end of October. We are not using previous assumptions, we were a little bit more optimistic. Based on the current level of events, we are speaking about is going to be by the end of October.
Now I will turn it to Mikael to speak a little bit about how comfortable we feel with the immunogenicity in elder population and what about the durability. As you can see also, Kathrin is on the panel, so maybe the technical problem has been resolved. Mikael, you start, and then Kathrin will add.
Thank you. As you could note in the presentation from Kathrin, we do have a very nice response in older adult, continued to rise at day 35 and being above you see in convalescent plasma. I want to point out that our vaccine, as you noted, induce also potent CD4 and the CD8 cells that Kathrin pointed out. The CD8 cells particular are great producers of an antiviral substance called interferon. Indeed, interferon determines susceptibility in studies for coronaviruses. Some of these data are coming from SARS-CoV-2, where patients that were protected from infections had CD8 cell activity for a very long time. Particularly as antibodies decline to intermediate level over time, the CD8 cells will be a very important additional tool. You have to look at the totality of strong immune response induced by our mRNA vaccines, including robust antiviral antibodies and CD8 cells.
Concerning the durability.
Angela spoke a bit to that we don't know yet. There are conflicting reports in durability after patients contracting disease and how long they retain protective antibody levels. We expect after a number of months from those patients that the antibody levels may settle at a lower amount, and then additional immune parameters may be additive. However, the advantage of vaccination is that you do that during a healthy immune status rather than when the immune status is perturbed by the virus. I do think we should have some cautious optimism that when you activate antibody CD4 and CD8 cells, there can be a reasonable long-lasting immune response. We will monitor this up to two years, and if required, longer. That will guide us when a possible additional boost should be given. Thank you very much.
Kathrin, anything to add to what Mikael said?
No, I think he covered it. Thank you very much.
Thank you. Let's go to the next question, please.
Your next question comes from David Risinger from Morgan Stanley.
I'm okay.
Yes, thanks very much, and thank you again for hosting. This is extremely helpful. I have three questions. First, certain political figures and news media have been challenging the legitimacy of science and judgment of the nation's top scientific leaders. How is Pfizer addressing these challenges? Second, slide 12 indicates an opportunity for a next-gen vaccine in 2021 that generates augmented immune response. What are you seeking to improve upon with respect to BNT162? Third, what is your understanding about the purpose of the FDA's planned COVID vaccine panel meeting on October 22nd? Thank you very much.
Kathrin, why don't you take the question about the next generation in 2021? What type of improvements do we anticipate to bring?
Yes, thank you for the question. What we are thinking about is, as Angela noted earlier, our current vaccine candidate is a frozen candidate. One of the improvements that we are going to think about is, can we produce a vaccine candidate that would have, let's say, a refrigerator stability profile? That's one. Another way of thinking about an improved COVID-19 vaccine is, as you know, and what I presented earlier, it is a two-dose vaccine. One of the ways to improve this vaccine would be to find a way to make it a one-dose vaccine. Those are two major things that we are thinking about in the context of what I would call a second-generation COVID-19 vaccine. Thank you.
Thank you, Kathrin. As regards the political environment, yes, it's very disappointing. Right now, unfortunately, the COVID crisis and particularly the vaccine's development, has been intensively politicized. We have politicians or journalists speaking about efficacy or safety about medicines, which, of course, is not appropriate. The scientists should be having these discussions. The pledge that we did together with other nine vaccine makers was something to address this, was our promise that no matter what others think, we will not ourselves submit, either for authorization or for full approval, data without having a conclusive readout of the phase III study. This is coming together with the reputation of our companies. As I said multiple times, ourselves, we are developing medicines for 171 years. We plan to honor this tradition, and we are not planning to stain it.
You asked for my comments about what I think the advisory committee that the FDA has called. I don't think it's appropriate for me to comment about what this committee will do. What I would say is that I'm very happy to see that FDA sends a very clear signal that they will use, in addition to their own staff experts, that they have seen it all, basically. They know exactly what to look when they are looking for safety or efficacy in a vaccine. In addition to that, they will use also the opinion of experts.
Your next question comes from Terence Flynn from Goldman Sachs.
Hi. Thanks for taking the question, thank you for all your work during the pandemic. I had two, maybe, Albert, just what do you see as the most underappreciated aspect of the Pfizer investment case right now? Obviously, we've listened to all the division heads over the last two days give us a pretty detailed overview, but would just be curious to get your thoughts there. On the COVID vaccine front, probably a question for Kathrin, but was wondering if you're capturing follow-up data on antibody levels from participants in the phase I trial. If so, are you able to share any details there about durability? Maybe you have access to blinded phase II, III data on the antibody levels. Would just be curious what you're seeing longer term on this front. Thank you.
Yes. Thank you very much. The investment thesis of Pfizer, I think I articulated very well in my opening comments yesterday. We have a very robust line of strong growing products. Last year, 8%, this year, first half, 9%. We have a pipeline that it is very diversified. It's not dependent on binary events. It is a pipeline that has multi assets. When you apply risk adjustments, it's meaningful because if you have, for example, five or six assets, maybe luck can weigh in different than what you think. When you have 20, statistics should work. In addition to that, it's very clear that we have the gift of no major LOEs all the way to 2025, 2026, basically to 2026.
With that, if you add the financial robustness of our company, all the cultural changes that we have done, the way that we are running the company, the proven record, for example, you see now how we jumped into developing a vaccine like COVID in a timeline that nobody would believe that Pfizer could have done this in the past. Of course, the fact that we have a very nice dividend that is going to grow, and also we have the financial flexibility to be able to enhance our pipeline with phase II, phase III assets. It is very clear, top-line organic growth, sustainable for the long term, and at least 6% in the midterm all the way to 2026. This is the investment thesis of Pfizer. Let me turn to Kathrin now to speak a little bit about the COVID-19 question.
Yeah. Thank you very much for the question. Like in all of our studies, we do actually evaluate persistence data. Those data will come primarily from our phase I studies, because they, of course, were started ahead of our pivotal phase III study. We're planning to look for persistence of antibody. We will also evaluate memory T cell responses, which I think particularly in the COVID-19 situation, as we described before, is very important to demonstrate that we have a good memory T cell response that will help us to address particular if neutralizing antibodies are waning with a strong memory T cell response. We have an opportunity or potential to provide a persistent protection. We cannot because we are blinded. You asked are there any data coming out of the pivotal phase III study?
Unfortunately, because we are blinded, we cannot access any data from our phase III study. Once the study is concluded, we will be able to publish the persistence data from phase III. Thank you.
Thank you, Kathrin. Next question, please.
Your next question comes from Geoffrey Porges from SVB Leerink. Geofrey, your line is open. You may proceed with your question.
Thank you very much. Congratulations on all the remarkable progress and the speed. A few questions on the pivotal trial. First, could you talk about the consent form that patients have signed and what obligation you have to the patients if you do get a positive efficacy readout? How will you manage the demands on the part of patients to get the active intervention? Of course, they have significant risk then if they are blinded, that they might go out into the community and expose themselves to COVID. On the other hand, you have the societal obligation to get the full safety data and to look at the durability of efficacy. How are you going to balance those two to get that information? Secondly, could you talk a little bit about the statistical plan for the phase III?
What sort of p- value and reduction in events do you need to see to unblind the study? Lastly, Angela, are you thinking about multiple vaccines being successful, or are you operating on the assumption that yours will be the only one?
Thank you very much. Let's start with Kathrin. The statistical plan and also about the consent form. How are we going to manage the situation when we have a conclusive readout?
Yes. Thank you for the question. Very important question. Let me start with the consent form. As part of the patient consent, we have made it clear, since we are not a diagnostic laboratory, that we would not provide on a real-time basis, any data that pertain to the PCR positivity status of SARS-CoV-2. However, after starting the baseline studies and we saw that actually we have individuals enrolling in the study that were already positive for SARS-CoV-2 at baseline, we made the decision that as soon as we have evidence that a participant is positive, we are talking baseline data here that we would notify the investigator to work with the participant in the appropriate manner. The second part of your question was the statistical analysis plan and what the plan is to define whether or not our vaccine is successful.
First of all, I need to say that we follow the very stringent guidelines of the FDA. The FDA has made it very clear that a vaccine has to be at least 50% effective with an observed 50% effectiveness, but the lower bound has to be more than 30%. Those are very stringent criteria. Our study is powered to be successful if we see at least 60% efficacy. This is just to say that it is powered and successful for at least 60%. That's not to say the vaccine will only be 60% efficacious, but it could be much more efficacious. I just wanted to make this clear.
In any case, whether at the final analysis or at the interim analysis, the intent is, of course, to analyze the data under those stringent conditions and make sure that whatever the efficacy is, that we can demonstrate that there's a lower bound above 30%. That's part of our statistical analysis plan.
Thank you, Kathrin. Mikael, anything to add here?
I think Kathrin described it great. Everything that you alluded to was with the original 30,000 participant. Now, as we even expand the trial, as we focus on additional groups that can be protected, of course, our power will, over time, be even stronger and overlap completely with the FDA minimum criteria. We do believe, given the very robust immune profile and also the preclinical profile protecting from infection, that vaccine efficacy is likely to be 60% or more.
Angela?
Thank you. Thanks for the question. I think you've heard today the very positive progress of our program, as well as the potential of the scientific profile that we expect to see from our program. I think that the science is just one aspect. One has to remember that the ability to manufacture at scale and the ability to distribute and to bring the supply chain is equally as important once we have the vaccine in our hands. This is where I think Pfizer brings its best to bear. We have the science, we have the supply chain, we have a track record of having done this over and over and over again. While I acknowledge that there are going to be multiple competitors out there, we are in a pandemic, a global pandemic.
What my assumption also is that we will have a strong leadership position in this.
All right. Let's get now our final question because we are a little bit over time. Our final question, please.
Hi. Thanks. Can it be final questions? First one I wanted to ask you was, how long do you think it will take to achieve herd immunity with viable vaccines? Outside of a clinical trial, how many percentage of patients do you think will come back for that second dose? Last question is, how representative are the convalescent serum data used as controls in the trials? Thank you.
Mikael, what do you think, how long it will take for herd immunity?
It's too early to know about that. Right now it's still a relatively small fraction of the population that have contracted disease, even with a larger estimate. The majority of the population across the globe has not contracted disease. We do hope, of course, assuming that we could conclude positively the trial, pending outcome and the regulatory aspect in October, that starting a vaccination across the globe to ensure herd immunity is what you would like to accomplish, but that will take time. We need to understand how long-lasting the immunity is, because in general, coronavirus immunity in natural infection have not been that long-lasting. That's why Angela spoke about that it may even require annual or every few years boost, which is, of course, a great advantage of this platform. In summary, I think it's too early to know.
We think this vaccine has potential to give reasonable and good protection, but we need to monitor, and it's reasonable also to assume that you need maybe in the future to boost, because this is a real pandemic, and there's going to be a lot of virus circulating even after global campaigns.
Kathrin, you want to take the other two questions about the trial?
Yes, I'm happy to. Thank you for the question. The question was of how many individuals and participants in the study come back for their second dose. As we said earlier, our vaccine is very well tolerated, we see actually very good compliance of trial participants to come back for their second shot. You ask about the relevance of our human convalescent serum panel. We have collected this panel. It's about a panel of 38 individuals. They were collected very early on as we started with our program, and they reflect what we see. They reflect individuals that are asymptomatic. They reflect individuals that showed symptomatic disease, there was also one of the 38 individuals was hospitalized. What we see now after generating more information, we see everything from individuals that have very low neutralizing antibodies, to very high neutralizing antibody responses.
The whole degree of what you would expect and what we do see right now in the real world. We believe that this panel is an appropriate panel to compare our vaccine-induced immune responses too.
Thank you, Kathrin. With that, I think we have reached the end of this two-day event. Before I share some closing thoughts, I want to thank my colleagues who served as presenters over the past two days. They are the ones that are driving Pfizer transformation, and the greatest strategists in the world are worth nothing unless they are executed well, and it is their ability to execute with excellence that have led. As I said yesterday, building upon a dramatic R&D turnaround that gives us one of the best biopharma organizations in the world, as we presented data yesterday. With improved success rates, reductions in cycle times. We have also taken the steps necessary to create the focus and culture that is needed to drive our success over the next decade.
We have clearly defined that the new Pfizer will be a highly focused, science-driven biopharmaceutical company. We put in place the people, the processes, the incentives, the operating model that enable us to deliver breakthrough science. Of course, we are playing to our strengths in six targeted therapeutic areas, where the intersection of new science, significant unmet medical need, and Pfizer's strong platforms and people give us a competitive advantage. We believe that this construct represents the greatest opportunity to deliver value for patients, for shareholders, and all stakeholders in both the near and the long term. Over the past two days, hopefully you have come to appreciate our deep passion in science and come to understand why we believe so strongly that science will win the battle against disease.
I'm thrilled that we're able to showcase some of Pfizer's top scientific and commercial leaders, to have an open dialogue with all of you, and to provide you with a better sense of depth and breadth of what we believe to be an industry-leading pipeline. When combined with our highly successful curated market portfolio, this pipeline, including what we believe are some undervalued programs, it is what makes us believe that we expect will allow us to sustain a revenue CAGR of at least 6% over the next five years and beyond. Thank you for your continued interest in Pfizer, our people, and our purpose. I hope you and your loved ones continue to stay safe and well, and I look forward to speaking with you all soon. Take care.