Good afternoon, and thank you for joining us to discuss Apellis' first quarter 2022 financial results. With me on the call are Co-founder and Chief Executive Officer, Dr. Cedric Francois, Chief Commercial Officer, Adam Townsend, Chief Medical Officer, Dr. Federico Grossi, and Chief Financial Officer, Tim Sullivan. Before we begin, I would like to point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Cedric.
Thank you all for joining us today. 2022 is off to an extraordinary start at Apellis as we continue to execute across each of our key priorities. Starting with intravitreal pegcetacoplan for geographic atrophy or GA, we've made important progress as we prepare for the NDA submission later this quarter. We completed the pre-NDA meeting in January, and then in March, we shared 18-month data from our phase III DERBY and OAKS studies, demonstrating that longer-term treatment with pegcetacoplan resulted in an increasing benefit to patients with greater amounts of retinal tissue saved over time and a favorable safety profile. Additionally, these data showed improving effects in DERBY that were comparable with OAKS starting at month six.
Just this week at ARVO, we shared additional 18-month data analyses that showed that pegcetacoplan reduced lesion growth in patients with extrafoveal lesions and in patients with foveal lesions, further supporting pegcetacoplan's benefits for a diverse population of patients across the GA disease spectrum. Collectively, these data reinforce the potential for pegcetacoplan to become the first-ever treatment for the millions of patients living with GA, a relentless disease that is a leading cause of blindness worldwide. Turning to EMPAVELI and PNH. The launch is off to a strong start in 2022, with approximately $12 million in U.S. net sales, despite the initial headwinds due to the Omicron variant. We remain focused on further establishing EMPAVELI as a first-line treatment for patients living with PNH. Our aim is to ensure that all patients with PNH, regardless of their baseline hemoglobin levels, have the potential to benefit from EMPAVELI.
The leading indicators for the launch remain strong with positive physician and patient feedback, a favorable patient mix, high levels of compliance, and positive recognition by payers. Globally, we are thrilled to see our partner, Sobi, begin to bring EMPAVELI, known also as Aspaveli in certain countries outside the U.S., to patients worldwide. Beyond PNH, we are seeking to advance EMPAVELI as a transformative therapy for rare complement-driven diseases. In the first quarter, we completed enrollment in our potentially registrational phase II study in amyotrophic lateral sclerosis or ALS, with top-line results expected in mid-2023. Additionally, Sobi dosed its first patient in a phase two study in hematopoietic stem cell transplant-associated thrombotic microangiopathy or HSCT-TMA. Together with Sobi, we now have two late-stage clinical programs underway and remain on track to initiate two additional programs in the second quarter.
Combined, these opportunities could address the needs of as many as 35,000 patients per year in the U.S. alone, significantly expanding the opportunity for EMPAVELI. We are also advancing complement inhibition as a novel approach to enabling adeno-associated viruses or AAVs. In collaboration with Spark Therapeutics, we look forward to sharing in vitro data with APL-9 at the upcoming annual meeting of the American Society of Gene & Cell Therapy later this month. While early, with additional clinical investigation warranted, these in vitro data further supports our hypothesis that complement, and specifically C3, plays an important role in anti-AAV responses, and that targeting C3 has the potential to help mitigate the safety and tolerability concerns associated with AAV delivery.
Finally, we are continuing to progress our early-stage pipeline with three INDs expected over the next 18 months, including APL-2006, APL-1030, and our siRNA program, and continue to make great progress in our partnership with Beam Therapeutics. On the finance side, we ended the first quarter with close to $1 billion in cash, providing runway into the first quarter of 2024. This strong financial position allows us to head into our NDA submission and potential launch from a position of strength in otherwise challenging market conditions. We look forward to building on our momentum as we further cement our position as a leader in complement across multiple therapeutic areas. Let me now turn the call over to Adam for a commercial update. Adam?
Thank you, Cedric. As Cedric mentioned, since our launch last May, we continue to see strong commercial launch results for EMPAVELI in PNH, resulting in $12.1 million in U.S. net sales for the first quarter. Before I get into the details of the launch, I'd like to take a moment to welcome Dr. Peter Hillmen to the Apellis team. Pete will be joining us from the University of Leeds as head of hematology engagement, effective later this month. Pete is an internationally recognized hematologist, clinical researcher, and thought leader in the PNH field, who has been involved in the development of several PNH treatments, including EMPAVELI. We are thrilled to have Pete coming on board and incredibly grateful for his continued contributions to the PNH community. Turning to the launch.
Since approval in May 2021 through the end of the first quarter, we saw continued positive momentum across our key leading indicators. More than 150 start forms have been submitted, with 30 received in the first quarter. We continue to see the vast majority of EMPAVELI patient starts coming from C5 inhibitor patient switches, with over 75% of these switches coming from Ultomiris. Another positive sign of demand is the continued growth of our REMS program, with approximately 170 physicians certified at the end of the first quarter. Additionally, 19 of the top 20 payers have added EMPAVELI to formulary. As we stated before, we initially focused on the top 20 payers, covering approximately 85% of all U.S. PNH prescriptions and are thrilled with the progress we've made within the first year.
One of the largest U.S. payers has also placed EMPAVELI as exclusive for all treatment-naive patients. Lastly, we are continuing to see high patient compliance rates in 2022, which we believe is a testament to the benefits of EMPAVELI and how much better patients feel when their disease is well controlled. As the quarter progressed, in-person access to physicians increased, and we saw a return of in-person conferences and events. This has allowed us to better connect with key HCPs who have been more difficult to engage with during the Omicron wave earlier this year. We look forward to further executing on our launch efforts in the U.S. and will continue to educate physicians, secure additional payer coverage, and bring EMPAVELI to patients in need of treatment.
Additionally, we've submitted our supplemental NDA, which includes the phase III PRINCE results in addition to the 48-week phase III PEGASUS data. If approved by the FDA, this will allow us to strengthen our promotion of EMPAVELI for treatment-naive patients and raise more awareness of our long-term efficacy and safety data. Turning to our commercial efforts in GA. 2022 will be a pivotal year for all of us here at Apellis and for the millions of patients suffering from GA globally. GA causes irreversible damage and is the leading cause of vision loss, impacting more than five million people worldwide, including one million people in the United States. We are compelled by the unmet need, loss of independence, and emotional burden of patients living with GA.
We recently shared results from a geographic atrophy insight survey referred to as GAINS, conducted by The Harris Poll on behalf of Apellis. GAINS surveyed over 200 adults with GA across nine countries. Results revealed that nearly seven in 10 people believe the impact on independence and quality of life due to their visual decline is worse than they expected. More than two out of three people reported that they rely on a caregiver for support, and a majority said that they feel the disease negatively affects aspects of everyday life, such as the ability to read, drive, and travel. Approximately one in three said they have recently withdrawn from their social lives because of their disease and reported feelings of anxiety, powerlessness, and frustration. It is overwhelmingly clear treatments are needed and needed now.
More than ever, we believe that pegcetacoplan is positioned to meet this significant unmet need, and we are committed to working to bring this therapy to as many patients as possible, as quickly as possible. Our commercial team is preparing for a potential launch as early as the end of the year. We have onboarded several of the key leadership positions in medical affairs, sales and marketing, and market access within the U.S. and additional leadership positions globally. We are initially focused on those retina specialists who manage the majority of GA patients. We also continue to make strides in our near-term launch initiatives focused on disease state education, KOL, and payer engagement activities. In the EU, we remain on track to submit our MAA in the second half of 2022. We look forward to providing more detail on our commercial plans as we prepare for launch.
I will now turn the call over to Fede to review our clinical developments. Fede?
Thank you, Adam. Submitting the NDA later this quarter is one of our highest priorities. As Cedric mentioned, we are excited to share the 18-month data from DERBY and OAKS. We showed continuous and clinically meaningful benefits to a diverse and broad group of patients over time. As highlighted on this slide, both monthly and every other month treatment with pegcetacoplan continued to reduce GA lesion growth compared to pooled sham at 18 months, with all nominal p- values below 0.05 in both DERBY and OAKS. This means that there was a larger absolute difference between pegcetacoplan and sham in GA lesion area than observed at month 12.
In an effort to understand how the treatment benefit evolved over time, we then look at the effects with pegcetacoplan at six-month intervals and found that the treatment effects in DERBY were comparable to OAKS during months six through 18. Pegcetacoplan in both studies continued to demonstrate a favorable safety profile, as shown in the FILLY study and the 12-month top line DERBY and OAKS data readout. Additionally, and most importantly, the combined 18-month data showed the potential for improved treatment effects over time. Earlier this week at the ARVO annual meeting, we and our collaborators had 10 presentations, including three oral presentations showcasing our leadership in the retina. In one of the oral presentations, we share 18-month data which showed that pegcetacoplan continued to demonstrate a reduction in GA lesion growth in patients with extrafoveal lesions and an improved effect in patients with foveal lesions.
In the combined DERBY and OAKS data, monthly and every other month, treatment with pegcetacoplan reduced extrafoveal lesion growth by 26% and 21%, respectively, and reduced foveal lesion growth by 13% in both arms. Nominal p- values were all below 0.05. This additional data reinforce the potential of pegcetacoplan to slow the progression of GA across the disease spectrum, which is critically important given the heterogeneity of this patient population. We are excited to potentially bring a therapy to all patients with GA, with an additional opportunity to treat early in disease progression and save as many photoreceptor cells as possible throughout the course of the disease. We're also excited to present the 18-month fellow eye compilation at an upcoming medical meeting, and expect the results to be generally consistent with what we saw at top line.
We're also working to deliver on the broad platform potential of EMPAVELI to advance our disease franchise, which includes four late-stage studies in multiple complement-driven diseases. In addition to what Cedric mentioned earlier regarding our LS and HSCT-TMA studies, we also expect to dose the first patient in a phase three study in immune complex membranoproliferative glomerulonephritis, or IC-MPGN, and C3 glomerulopathy, or C3G, in the second quarter. Our partner, Sobi, remains on track to initiate a phase three study in cold agglutinin disease, or CAD, in the second quarter. We're excited to share our continuous progress across these rare disease programs. Let me now turn the call over to Tim for a review of the financials. Tim?
Thank you, Fede. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the first quarter of 2022. Total revenue was $14.4 million, which consisted of $12.1 million in EMPAVELI net product revenue and $2.3 million in collaboration revenue from Sobi. R&D expenses were $90.9 million, G&A expenses were $51.2 million, and we reported a net loss of $138.9 million. As of March 31, 2022, Apellis had $965.3 million in cash equivalents, and short-term marketable securities, excluding the additional $50 million milestone received in April from Sobi. Our cash balance reflects $380.1 million in net proceeds from our offering in March.
We expect our current cash balance to fund our operations into the first quarter of 2024, including the ongoing EMPAVELI launch, the global launch of pegcetacoplan and GA, and further development of our pipeline. We remain confident in Apellis' financial future as we continue to execute on our upcoming milestones. I will now turn the call back over to Cedric for closing remarks. Cedric?
Thank you, Tim. We have made excellent progress over the past few months and look forward to an exciting rest of the year. By year-end, we expect to have further cemented our position as a global leader in complement with two commercial products and a robust pipeline encompassing multiple late-stage rare disease programs and additional preclinical programs heading into the clinic. We look forward to building on the company's momentum throughout the coming year and to updating you on our progress. Let us now open the call for questions. Operator?
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Our first question comes from the line of Madhu Kumar with Goldman Sachs.
Oh, hey, guys. Thanks for taking our questions. I guess our first one relates to the European filing strategy for pegcetacoplan. How should we think about that? Do they need to see the 24-month data both in terms of GA lesion growth and in terms of functional assessments of vision before you kind of formally start the process of filing for approval in Europe?
Thank you so much, Madhu. Great to hear you. We are meeting with the rapporteurs in Europe, and those interactions are going very well. Our plan continues to be to file in the second half of this year. As you mentioned, the 24-month data is something that you know will be updated in that package. The functional endpoints, I want to again point out you know that the expectation there should not be to see something statistical. It never was. The European regulators want to understand what the functional relationship is with the photoreceptor cell death that we measure with the anatomical endpoint. All of that will be included. Again, the second half of this year continues to be our guidance.
Okay. Then one more question on GA market size. A question we kind of have been getting more recently is what fraction of GA patients are functionally or legally blind in one eye? How does that affect kind of the treatment decision versus patients who have functional vision in both eyes? Like have you guys started looking at that question, and what are you hearing out there?
Thank you, Madhu, for that question. The number there is around 40% of patients. It's a very high number of patients who, you know, are legally blind in one eye and affected by GA in the fellow eye. That is particularly a target population that is of interest for many retina docs because, of course, those are the patients that are most at risk of catastrophic bilateral vision loss.
Okay. Thanks very much, guys.
Thank you, Madhu.
Thank you. Our next question comes from the line of Jon Miller with Evercore.
Hi, guys. Thanks so much for taking the question. I guess one on cash runway. I guess into 2024 seems to get you well into the launch, but what's the likelihood that that can get you to profitability? And given the new runway, you know, how have BD priorities and discussions shifted since the recent raise?
Thanks. I'm gonna hand that one over to Tim.
Sure. Thanks, Jon. You know, with this recent capital raise, you know, as you said, our runway does get us into the first quarter of 2024. In terms of that, you know, there are a lot of assumptions out there that could, you know, fluctuate that kind of target of profitability one way or the other. You know, we're not guiding to profitability based on that timeframe. However, you know, I don't think that capital really gets us a comfortable cash balance if we get to profitability. We're gonna continue to be thoughtful about what, you know, what that potential financing that would get us there looks like. We're looking at approaches. It may include debt, royalty, partnerships or other financing vehicle.
You know, the good news is that we have a very strong cash balance right now, and we can take our time to figure out what makes sense for the company.
Great. That makes sense. Maybe one more follow-on on the 24-month data we just were discussing. When we think about FDA, if they get that 24-month data, you know, later this year, what's the likelihood that constitutes a major amendment and pushes out the PDUFA?
Yeah. Thank you, Jon. The likelihood of that is very, very small, and would be based on surprises, right? We have of course amply discussed this in anticipation. The reason why the 24-month data is not something we need to wait for is because we don't expect to learn anything new between month 18 and 24. Of course, when we have the data, we will communicate it, but it's not scheduled to be a major amendment.
Great. Thanks very much.
Thank you.
Thank you. Our next question comes from the line of Phil Nadeau with Cowen and Company.
Good afternoon. Thanks for taking our questions. A couple more on regulatory. In terms of an FDA panel, what are your expectations? Do you think the FDA would wanna hold one? And if so, what would they hope to learn? And then second, on the timing, we noticed on slide 13 you suggested that an approval is possible this year. Our understanding of the regs at the FDA is they have two months to accept any filing, and then even with priority review, it's six months after the acceptance for the PDUFA. So it seems like even if we were to file today, the 2023 PDUFA day would be likely. We're curious what you heard from the FDA that gives you some confidence that an approval could actually come before the end of this year. Thanks.
Yeah. Thank you so much, Phil. Two great questions. I'm gonna start with the second one. The six months from the time of acceptance is a timeline that depends on a new chemical entity. But because pegcetacoplan is already approved in a different product, of course, it is no longer a new chemical entity, and that would mean six months from the time of filing rather than acceptance, and that would, of course, you know, put us at the end of this year still, even if it were to be at the end of the second quarter. Now, as it relates to the FDA panel, we are operating under the assumption that there will be one. We will be ready to have one.
It is, of course, potentially the very first approval in this very important new indication. I think when we think about what could be discussed during a panel like that, I wanna remind people that the way in which the NDA is being submitted kind of is centered around with four cornerstones, right? The first one is safety. The second one is the biological activity of the drug. Does it work? That is premised on meeting the primary endpoint in two studies, FILLY and OAKS, and then on the fellow eye analysis in patients with bilateral GA. The third chapter or the third cornerstone is then what is the real effect size?
Because between the three studies that we have, we have an effect size ranging from 12% to 29%, and with the covariates analysis, clearly at one year, clearly sits around 20%. The fourth cornerstone is what happens going into year two. Of course, you know, that was one of the foundational principles of including the 18-month data as well, where we want to understand what is the long-term impact of treatment with this drug in the disease that people will have for years, if not decades. In the context of an outcome, should there be one? Kind of the only subject that is really, you know, kind of interesting one is what does 20% at one year mean? What does kind of the continued benefits over time mean for patients in terms of saved photoreceptor cells?
We do not believe that, other than that, there are many controversial elements in this submission.
It sounds like you think a panel would go into that major subject of kind of what's the clinical significance of the data or of the event, of the results that you're showing. Is that. Am I interpreting what you're saying correctly?
Yeah. The question was, if you have a panel, what would be discussed? I think that would be kind of the
Okay.
Probably the fix. Now we have done a ton of research on that, of course, in the preparation for the launch. The general consensus among physicians is that 20% is clinically meaningful, so it's also not a subject that we believe will be problematic for us.
Got it. Thanks for taking the question. That's very helpful.
You're welcome.
Thank you. Our next question comes from Steven Seedhouse with Raymond James.
Yes. Hi, this is Timur Ivannikov on for Steven Seedhouse. Just a question on GA. I think you've talked about the importance of educating retina docs. Assuming the drug is approved, what do you think will be the best way to communicate the benefit of pegcetacoplan if a patient doesn't really see a change in symptoms over a year or maybe the symptoms are worse, but it's not really clear whether the drug is helping?
Yeah. Thank you so much for that question, Timur. I think it's a very important one, right? I mean, I would say that what most resonates with retina doctors is when you talk to them about the area of saved retina, right? I mean, that's a very tangible thing to look at, right? I mean, it's not a percentage slowdown or whatever. It's how much retina is actually being preserved. We disclosed the number with the 18-month data of OAKS, for example, where at one year, 0.41 sq mm of retina was preserved compared to the sham, whereas at 18 months that was already 0.66 sq mm. You could say, "Well, what is a square millimeter in the retina?" Well, think about it this way.
You know, approximately or even less than 2 sq mm is responsible for all of our central vision. What we need to read charts in which, you know, determines visual acuity. That is a lot of retina over the course of, you could say, year and a half, a lot, but in the picture of a treatment with GA, a very short period of time.
Okay. Got it. Thank you. Maybe just a quick follow-up. In terms of fast progressors that you've talked about in DERBY, on the other hand, do you have people who are best responders, who are deep responders? Do you have patients who, you know, did not really progress at all on GA? If you do, what is the distribution of those patients across the studies?
Those are details that over time we will talk about more. It is very rare for patients to not progress at all. That can occur, of course, but it's rare. It's a Gaussian distribution, right? It goes from very fast to no progression at all. How exactly that pans out, we will in due time publish. What's important is that we have many variables that can drive how fast these patients progress. It's easy for a study to be out of balance because you can, quite frankly, not stratify a study properly in GA to really be well-balanced. Sometimes you can get lucky. In FILLY, for example, we probably were lucky in terms of the distribution of the patients between sham and actives.
Whereas in DERBY, you know, we were unfortunate, right? In the sense that, as you mentioned, these very rapidly progressive patients were disproportionately allocated to the active monthly arm.
Okay. Thank you very much.
You're welcome.
Thank you. Our next question comes from the line of Chris Howerton with Jefferies.
Hi, team. This is Kumbi Zhang for Chris Howerton. Thank you for taking our questions. Couple questions for us. What were your takeaways from the DERBY extrafoveal subgroup analysis? Were you surprised to see every other month performing better than monthly in that group? I guess just any general broader takeaways in GA from that finding. As a second question, thinking about kind of function and how pegcetacoplan will impact patients' visual function, what's the most high fidelity functional measure in GA? And kind of, like, what's the most practical way to measure function? Would something like a digital Amsler grid be practical and easy to implement to measure visual function? Thank you.
Thank you so much, Kumbi. Let me start with the extrafoveal question. Here too, you know, by the way, the 12-month data on extrafoveal, we also disclosed, I believe it was at Retina Society in the beginning of October, right? To continue, we do have an inverse dose relationship there, but one that will be interesting to see how it continues to progress over time, right? There you see the true manifestation of what I mentioned earlier, which is that in DERBY, in the monthly arm, not in every other month, but in monthly we have these rapidly progressing patients, right? They are at a disadvantage compared to the sham, and they're even at a disadvantage compared to every other month.
What's very interesting and beautiful to see is how over time that compensates, you know, which we also clearly disclosed in the 18-month update that we gave in March. As it relates to function. One of the big problems that we have in geographic atrophy, but in the retina in general, is that measuring function is very difficult and incomplete in the retina, right? You can say visual acuity, for example, which is the best known. Well, that only measures your central vision. To read a chart, what you need is the central portion of your vision, and you could read a chart looking through a straw if you wanted to.
If I told you to run across a street looking through a straw, of course, that gives you an idea how poor of a measure for function that really is, right? We then have some visual questionnaires that can be helpful, again, to understanding how function evolves, but they're also incomplete. Reading speed is another one, but that one too varies widely, within the same patient, right? I mean, your reading speed in the morning is different from the evening, for example. Microperimetry is a really interesting one. It's an intense examination, takes several hours, where we shine a laser with different frequencies in the back, with several spots. Again, there the number of spots you can test are limited. So all of these things have their limitations, and they kind of provide a contextual context.
What is important, and this is the reason why the FDA and every regulatory organization that we deal with has accepted the anatomical endpoint of autofluorescence over time, is that it measures directly how quickly retinal cells die, right? Yes, it's an anatomical endpoint, but with almost close to single cell resolution, right, we can measure how quickly patients are actually losing photoreceptor cells, which is directly correlated to vision.
Thank you so much.
You're welcome.
Thank you. Our next question comes from the line of Colleen Kusy with Baird.
Hi. Good afternoon. Thanks for taking our questions. I think in the 18-month update, we did see some of the slope analysis. I guess, do you have a sense of the FDA's view on the slope analysis, and would they care about the entirety, so, you know, like 0-12 or 0-18, or could that be more heavily weighted towards the later slope, so say months 12-18?
Thank you so much, Colleen. That is a really great question. Again, kind of going back to the way in which our primary endpoint is measured, right, we look at lesion size reduction over time. That is what we agreed on with the FDA, and that is the way we do the primary endpoint analysis. However, in secondary analysis, among many other things, we do a slope analysis. The slope analysis gives you exactly the same outcome as you get for the measurement of loss over time. It's close to exactly the same. You make a very important and in my opinion, really critical point, which is also the slope can be measured in various ways. You can go from, for example, over one year from zero to 12 months.
You can go from zero to six months, six to 12, or you could even go from 12 to 18, the way we did it, at the 18-month time point. That is important because the slope gives you an idea of what to expect over time and how consistent the measurements are among each other. It is a contextual tool to understand what the long-term impact of treatment is on patients. What we showed with the 18-month data in March is that if you take it through this piecewise linear slope analysis from zero to six to 12, and 12 to 18, that these effects seem to be compounded, right? If I have geographic atrophy today, it's not that important how bad my disease was two years ago or 18 months ago.
I care about what it is like now because that is what I will in all likelihood carry forward as long as I stay on treatment, right? In that sense, the 12-18-month data looked very good with data much more consistent between DERBY and OAKS, for example, at the beginning of the study.
Great. Thank you. That's really interesting. On a potential GA launch, I guess how much focus will be on retina specialists that are already seeing probably more advanced GA patients? How much focus will be on educating optometrists or general ophthalmologists on referring earlier-stage GA patients to specialists?
Yeah. Thank you so much, Colleen. I'm going to hand that one over to Adam.
Thanks, Colleen. Thanks for the question. A quick little reminder, right? We'll target around 3,000 retina specialists and some optometrists as well, right, to drive patients who are unaware that there's a treatment to a retina specialist. Our focus is on a target list of about 3,000. An interesting piece of information, right? About 900 retina specialists do about 85% of all of the intravitreal injections for anti-VEGF. It's a really concise group of retina physicians that do the bulk of the injecting. It's a very easy target for us to go and introduce ourselves to and start to build commercial relationships with. As we said on the call, we started to onboard several of our leadership positions across commercial, medical affairs, sales, and marketing.
Interestingly enough, we started our high-level leadership sales position recruiting, and we had over 400 resumes come in for those positions. You can see the interest within the industry on the potential excitement around our GA launch. Hopefully that answers your question, Colleen.
Yes, it does. Thank you. Thanks for taking our questions.
Thank you. Our next question comes from the line of Derek Archila with Wells Fargo.
Hey, thanks, good afternoon. Thanks for taking the questions. Maybe just shifting gears to PNH and EMPAVELI for a sec, just two questions. I mean, first, I guess how has the EMPAVELI patient mix trended in terms of naive versus C5 switches, you know, since launch? That's question number one. Second question, I guess, can you talk to what the competitors are doing in this market right now? Are you starting to see some more counter-detailing, you know, since you've been in the market for now, you know, more than several months? That would be helpful. Thanks.
Thank you, Derek. This one too, I will hand over to Adam.
Yeah, thanks, Derek. Thanks for the question. Not a surprise, we're finding that C5 inhibitor switch patients continue to be the majority of our EMPAVELI starts. As a reminder, we know there's 1,500 C5-treated patients within the U.S. and 150 treatment-naive patients, give or take. Again, consistently 75% of the switches are coming from Ultomiris patients. That just tells you that the benefit that people see of a C3 treatment over a C5 treatment. We are also seeing patients with hemoglobin levels near normal that have experienced the benefits of EMPAVELI. Patients from this group will still potentially suffer from, you know, symptoms such as jaundice and fatigue. We're seeing that the higher levels of hemoglobin are now entering the market and asking to switch and switching to EMPAVELI.
We continue to see treatment-naive patients come in, as well to EMPAVELI, and they're also benefiting from the significant increase in hemoglobin. As we get later into the launch of this year, I expect us to continue to build on that C5 switch population, to continue to drive higher hemoglobin patients on C5 to C3 to EMPAVELI. I expect the treatment-naive patients to also increase. I think we're getting a whole mix of patients within the market that are benefiting from switching to EMPAVELI. Now the second part of your question, competitors and what we're seeing. One thing I'll say, Derek, is we are laser-focused on executing our plan.
For me, that's best practice as we launch into these ultra-rare diseases to make sure that we offer the best solutions for EMPAVELI patients and also hematologists and oncologists that are willing to put patients on EMPAVELI. We try and make sure that when we hear about competitors and everything that's happening in the market, that we just stay true to our plan, which is we want to elevate the standard of care for PNH patients. We have not surprisingly seen, you know, more action and noise from various companies. Again, we are determined that we have the best products, and we believe that we have the best impact on patients, so we're gonna continue to execute our plan.
We tend to listen to the noise, ignore it, and stay focused and true to what we wanted to execute in the market.
Got it. Thanks, guys. Thanks, Adam.
Thank you. Our next question comes from the line of Yigal Nochomovitz with Citigroup.
Hi, Cedric and team. Thank you very much for taking the question. Cedric, I have a question on effect size for extrafoveal and foveal subtypes. Obviously in extrafoveal the data are very, very strong for both OAKS and DERBY. For foveal, the situation, as you know, is a bit more complicated since the data looked really good in OAKS but not quite as good in DERBY, though of course, on a pooled basis, foveal still shows a very solid signal and is now in effect at 18 months. With that being said, what is your level of confidence you can get claims to foveal in the label?
More to the point, how mission-critical is a foveal claim, given that these patients already have irreversible central vision loss and retina docs will have more opportunities to save vision if they can start treating patients with the extrafoveal lesions?
Thank you so much, Yigal. That's a very good and important question, because I think it's worth briefly speaking about these foveal involvement. Foveal lesions are lesions that, as you know, sit centrally and have affected the fovea and therefore have a dramatic effect on the patient as opposed to extrafoveal lesions where the central vision is preserved, but the periphery is affected. Newly diagnosed patients get diagnosed initially with extrafoveal lesions, because there is, for reasons that we don't fully understand, the fovea often protected until the very, very end of the disease progression. It is a fair assumption that foveal patients you should think of as more advanced patients compared to extrafoveal patients, particularly the earlier ones.
Those advanced patients, even when fovea becomes involved, however, can still rely very heavily on whatever retina is available to them outside of the fovea. Those patients, you know, when they get to that time point, you don't want to stop dosing or treating. You know, if anything you want to consider being even more aggressive because these patients are the ones that are really losing the most most quick. To your point, in DERBY, the foveal patients, you know, did not show a lot of effect. In OAKS they did. Once again, most fascinating to see how over time that seems. We're going to continue to follow that. The way in which the study was done on the primary endpoint is we included all patients with foveal as well as extrafoveal.
Once you start diving into the foveal, you always have to be careful with the fact, of course, that you're dealing with smaller patient populations where random effects can have a bigger. To be continued, but our tracking will be on all patients with geographic atrophy, foveal as well as extrafoveal.
Okay, great. Thanks. Just on the dosing regimen for pegcetacoplan and GA. As you know, you know, there doesn't appear to be a clear dose response between monthly and every other month. You know, as for example, the extrafoveal every other month and monthly dose responses are inverted between OAKS and DERBY. I'm just wondering, is there any credence to the argument that the agency should only approve every other month, given comparable efficacy to monthly and an incrementally cleaner safety profile on new onset CNV? Or do you disagree with that assertion and believe both schedules merit approval?
Yeah. Look, we're very excited about the every other month dosing schedule, right? I think especially for patients with extrafoveal lesions at the beginning of the disease, you know, who want to preserve as much vision as possible. If you end up getting, you know, 80%-90% of the benefit of monthly injections by doing every other month, you know, that is desirable if you start early and you want to get as much as possible over the long run. We think that is a very important piece of our filing. There's also the 18-month data that we have. Not just 12, but we have the full data package on the 18 months, both on safety as well as on efficacy.
Of course, as we discussed earlier, kind of the improving effect profile that we see on these foveal patients as well over time. I think that in terms of the dosing regimen, both doses, we believe, have the data necessary to get approved. We do not believe that the safety profile warrants limiting the label, and we would like to provide as much flexibility as possible to the physicians. Importantly, again, you don't get the full benefit, right? Just touching as I did in the previous question on that every other month versus monthly inversion in DERBY, that is related to the fact that we had rapidly progressing patients in the monthly arm. If you look at the totality of the data, monthly has a slight benefit over every other month without a doubt.
Thank you. Our next question comes from the line of Eliana Merle with UBS.
Hey, guys. Thanks for taking the question. Just in terms of the GA sort of commercial landscape and any sort of pre-commercialization kind of analysis that you guys are doing. I guess what data do you have or sort of what's, you know, kind of your latest understanding of sort of the number of patients that might be undiagnosed today, just given sort of no available treatment, so maybe not an incentive to actively diagnose and how you're thinking about that, just as we all kind of run sort of the, you know, standard kind of model in terms of the number of patients that might be out there with GA.
Thank you so much, Eli. I will hand that one over to Adam as well.
Thanks, Eli. A quick refresher. Obviously five million GA patients worldwide, one million alone in the U.S. Now, in our discussions with retina physicians, we've got to a level where a lot of retina physicians believe that that number is actually greater than one million patients because of patients that might not make it to their retina center or to an injecting ophthalmologist or something like that. I think, if you speak to the experts within the field, they'll tell you that number could be higher than that. For all intents and purposes, we're focusing on that one million, and we're looking at various ways, including targeting certain optometrists and ophthalmologists to allow that drive of the patient, now that there's a potential treatment on the horizon to an injecting retina specialist.
We're also exploring various ways through digital footprint disease education and awareness to really make it known to patients through various channels that they could and should potentially go and see their retina specialists or injecting physicians. We've looked at a lot of those type of activities. We have plans around that. We do think it's gonna be important to make sure that we can drive patients to injecting physicians. Hopefully, Eli, that answers your question.
That's helpful. Thanks.
Thank you. Our next question comes from the line of Joseph Stringer with Needham & Company.
Hi, good afternoon. Thanks for taking our questions. One on PNH. Both that you've added, based on your start forms, 25 were the last over the last two quarters. Just curious if you see this sort of reaching sort of a steady state, and were there any impacts on start forms in COVID-related in 1Q? Just on the compliance rate remains quite high. Do you still expect this to remain this high, or where do you see the compliance rate sort of leveling out at? Thanks for taking our questions.
Thank you, Joey. Adam?
Yep. Thanks, Joey. I think we believe that we're gonna see consistent growth quarter over a quarter in an ultra-rare disease like PNH. It's incredibly encouraging that we continue to see that demand, especially to your point, Joey, in light of the COVID-19 restrictions, which thankfully we're seeing now as we exit the first quarter, lifting a little bit and access is improving for sure. That allows us to get back into physicians' offices and, you know, train patients, more frequently face to face. I do expect some fluctuation when it comes to start forms, right? This is our first January, February, and March for an approved product in EMPAVELI, right? We're learning the seasonality, we're learning the impact. I'm pleased with the consistent, demand that we're seeing when it comes to start forms.
Another good metric for everyone to think about is we continue to see REMS certifications and programs increase. We had over 170 physicians sign up for our REMS, our REMS program. That continues to grow. And that's another good sign for everything that's coming there. More to come. I expect the demand to continue. Everything we're hearing from physicians and patients points in that direction.
Great. Thank you.
Thank you. Our next question comes from the line of Laura Chico with Wedbush Securities.
Good afternoon. Thanks for taking the question. I kind of wanted to follow up on one on the commercial side for GA, and I think you discussed this a little bit, but what is the capacity of the system in the U.S. to treat or to handle IVT injections by ophthalmologists and retinal specialists? I'm just trying to understand how many patients could feasibly be treated more at a peak period, but as we're ramping up. Kind of related to that, what would be the timeline to obtaining a J-code? I'm just curious how that might impact uptake during the period prior to issuance of the J-code. Thanks.
Yeah. Thank you, Laura. Those are two excellent questions. I'm gonna hand it over to Adam, but very briefly on the capacity level. I think one of the things that is really great is that the infrastructure, the reimbursement model, you know, the habit that retina doctors have of administering anti-VEGF products is of course the perfect point of entry for us, right? The fact that we're talking about capacity rather than capability is a great point for us to start from because all of these physicians, these retina docs, are used to managing inventory, the buy and bill model that is typical for these products. We are slowly entering into a phase where with anti-VEGF injections, everything goes towards fewer anti-VEGF injections, where less frequent dosing will hopefully become possible.
In many ways, you know, there is a scenario here where the introduction of our product should, if and when it occurs, help us kind of fill what would otherwise be a void that gets created by less frequent dosing on anti-VEGF. Adam, I'm going to hand it to you to talk more about that as well as to comment on the J-code, please.
Yeah. Thanks, Cedric, and thanks, Laura. Yeah, Cedric, you said it very well. I mean, we did some capacity research last year on our products and one thing we found consistently, as Cedric said, is that you know, retina physicians know how to make sure that they can get their patients in and treated with the wet AMD as a great analog. But they also consistently told us that they knew what it would take to allow them to improve that capacity, be it a new bed or a new seat or a new technician to help onboard patients. They already had started to think of plans should capacity be an issue.
I think if capacity is gonna be an issue, which I don't expect it will be earlier on in the launch phase window as people are getting, you know, the product approved potentially, and then people are starting to identify patients and bring them in. I think in the initial phase of the launch window, that's when we would see any headwinds there. We have plans on how we could help do that, and we have a pretty good piece of robust research that helps us do it. It's also tied to your second part of your question around J-code. Obviously, you know, a little bit of a refresher for people. All new physician-administered drugs, like this one, they're billed through miscellaneous J-codes, right?
We expect at launch that we would have that type of miscellaneous J-code, and then we'll work with CMS, and permanent J-codes are awarded, as probably most people know, on a quarterly basis, January, April, July, and October, off the top of my head. We understand the impact of that, right? We understand that providers are gonna be relatively sensitive around the certainty of reimbursement for these type of drugs. I think they're gonna take that into account as they look in the early stage of the launch until a permanent J-code becomes effective for them. We're looking also based on the capacity question, we're looking at various ways that we can help support that provider confidence in prescribing our product as quickly as is possible.
We'll obviously apply and obtain a permanent J-code to help facilitate all of the claims processing and payment. I expect that to be within hopefully 6-9 months of approval. That's where we stand on all things J-code.
Thanks, guys.
Thank you, Laura.
Thank you. I'll now turn the call back over to CEO Cedric Francois for any closing remarks.
Thank you very much. In closing, thank you all for joining us today. We look forward to keeping you updated on our progress in the months ahead. We are around later today and tomorrow. If you have any additional questions, feel free, of course, to reach out to Meredith, and have a wonderful rest of the week.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.