Vertex Pharmaceuticals Incorporated (VRTX)
NASDAQ: VRTX · Real-Time Price · USD
426.01
-4.28 (-0.99%)
At close: Apr 27, 2026, 4:00 PM EDT
425.82
-0.19 (-0.04%)
After-hours: Apr 27, 2026, 6:23 PM EDT
← View all transcripts

TD Cowen 44th Annual Health Care Conference

Mar 5, 2024

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Good morning, and welcome once again to TD Cowen's 44th Annual Healthcare Conference. I'm Phil Nadeau, one of the biotech analysts, and it's my pleasure to moderate a fireside chat with Vertex, one of the bellwethers of the industry. We have with us today David Altshuler, the Executive Vice President of Research and CSO, as well as Charlie Wagner, the EVP and CFO. I guess I'll hand it to you guys to give a state of the company overview. What are the challenges? What are the strengths, and what does Vertex do over the next 12-24 months to create value?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah, Phil, thanks. Thanks for hosting. Happy to be back at the conference. We will make some forward-looking statements, so I encourage people to take a look at our recent SEC filings. Phil, it's an incredibly exciting and dynamic time at Vertex right now. Just think back over the last 90 days or so, we've had multiple approvals for Casgevy.

We've released positive data in our pain program, both in DPN and in acute. We've released positive data for our Vanza triple combo. We have, you know, done our earnings call, reported a great fourth quarter, given strong guidance for the year. It's been an incredible 90 days. And so where do we go from here?

As we get into 2024, we look forward to treating more patients with CF, with Trikafta, but also preparing for the launch of Vanza. We look forward to launching Casgevy in multiple countries in the U.S., in Europe, and in the Middle East. We look forward to more data in the pain program and filing in acute pain in the middle of the year, and filing for Vanza in the middle of the year as well.

Also advancing our pipeline in a number of different programs, notably type 1 diabetes and AMKD. So, a really full slate for the year. I would note that with the Casgevy launch, this will be the first time in more than 10 years that Vertex has revenues outside of CF.

W e really look at this as the first step in an era of commercial diversification for the company. We see additional launches in pain and with Vanza, and making significant progress towards our goal of five launches in five years. So all I can say is that, we're all incredibly enthusiastic and busy right now, and it's really rewarding to see how our approach to serial innovation and focusing on transformative medicines for serious diseases is creating incredible value for patients and for shareholders. So with that, let me open it up to questions.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Sure. So I think investors are actually now focused outside of CF and probably most focused on pain. You referenced the positive data we saw from the pivotal trial for VX-548. For those less familiar, can you summarize the data briefly and talk about what Vertex is most enthusiastic about in the profile?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Sure. Excuse my voice, it's a little bit worse. We're very excited about the data. We designed this phase 3 program in consultation with the FDA, with the goal of achieving a broad, acute pain, moderate to severe acute pain label, and the study met every expectation we had. There were three different studies. They all met their primary endpoint with very great statistical significance, but also clinical significance. So, for example, the reduction in pain in both the abdominoplasty and the bunionectomy study was 3.4 points, or about a 48% and 52% reduction, where actually 2 points and 30% is considered clinically meaningful.

In addition, all the secondary endpoints, you know, that we studied, we did do the next study, which was: Was it superior to the opioid comparator, which is actually a combination of opioid and Tylenol, but we used Norco because it's about a third of all patients treated with acute pain are treated with that, and the results were essentially very similar. And we could talk more about the bunionectomy, et cetera. Equally or perhaps important is the safety and tolerability.

A s people know, the problem with opioids is not that they don't have efficacy. The problem is they have significant safety and tolerability issues, as well as addictive potential. I think the safety and tolerability is actually under-recognized by some people in terms of how bad people feel, many of them, taking opioids.

There are some people who feel really good, they tend to be the ones who are more likely to get addicted, but a lot of people find the nausea, sort of feeling spacey, the sleeping on the couch, not feeling like they can drive, et cetera, to be quite intolerable. The key thing about our studies was across the studies, the number of adverse events—there were no SAEs, and the number of adverse events was actually lower than placebo. We saw those results, we all looked at each other because we couldn't think of another... We had three studies, 2,300 people or 2,000 people in the placebo-controlled trials. The actual rate of AEs was lower.

I think that a medicine that can provide that kind of pain relief, and people actually feel good, they feel alert, they're able to go to their jobs, they're able to, like, you know, have energy and all that, I think will be a transformative medicine. One other point I wanted to make, and then I'll stop. Next, we also did a study.

Those two studies were a hard tissue model and a soft tissue model, bunionectomy, abdominoplasty. We also just studied 250 people with different kinds of pain conditions, like broken bones or twisted ankles or other surgeries in a variety of settings, emergency rooms, hospitals, outpatient. In that study, 83% of people said they had a good, very good, or excellent pain control.

All the data is just what we thought we were looking for to get an approval for moderate to severe, broad acute pain label, and we'll be filing mid-year for that.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

We hosted a panel yesterday with pain experts, and one point that they made is that they do want to see the full data, they want to see additional endpoints. In particular, one physician mentioned something called the double stopwatch test, which I admit I'm not all that familiar with. When will you announce the full data? What other endpoints can we expect to see, and did you do that stopwatch test for VX-548?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

A couple of things. We will be presenting the data at a scientific meeting and publication. That's where we'll provide more information. I think we disclosed, actually, when we presented the data, what some of the secondary endpoints are, sort of usual things. With regard to rapidity of onset, there are two things, but if you look, we saw rapid onset much faster than placebo, and there's sort of two measures. One is like when, actually, the classical measure is like when it drops one point, and then, but we're more interested, frankly, in the clinically significant two points number.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Exactly.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

T hose are all very rapid. The people we worked on were very happy, and I think that something else that was said, it's just not true, is that any of that was important to approval. We worked with the FDA. They worked with us. We designed the study. We know exactly what we need. We have what we need.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

On the side effects, you did reference the AEs being less than placebo. Can you talk about that a little bit more? That not only were they less than a placebo, they're also obviously less than Vicodin.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

How important is that to uptake? To what do you attribute to that?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Well, sure. Yes, they were better than placebo, and obviously, they were better than the opioid. And the key thing to understand is that you cannot possibly separate the side effects of an opioid from the activity, the pain relief, 'cause they're the same thing. It's the same receptors. Like, there's no way to design an opioid that doesn't have all the side effects.

In fact, when I was in medical school, I remember learning that the way opioids work, and it is true, is they don't actually reduce pain. They change your perception of pain. So when my good friends broke his lower leg when we were in medical school, we went to the Brigham Emergency Room. They put him on a morphine drip. We went and saw him.

I said, "How are you feeling?" And he goes, "Oh, the pain's unbelievable," and he smiled. I said, "Well, why are you smiling?" He goes, "I don't care." That's true, though. That's actually what opioids do. They're CNS acting, but they also act on your gut to constipate you. They also suppress respiration. They make you dizzy. They make you sort of feel out of it and all that stuff.

That's not separable. Our medicine, one, is highly selective, 30,000-fold selective, for example, for other sodium channels, and the target, which is the only thing it hits, we also tested like hundreds of other receptors and all that, is only expressed in the pain-sensing peripheral neurons. That's known from biology, it's known from human genetics, it's known from all this.

W e are only acting in the peripheral nerve to block pain signaling, and that's why there's no CNS effects. You know, for diabetic peripheral neuropathy, we'll get to that later if you want, people use what's called Lyrica. I don't know if people know what Lyrica is. It's an anticonvulsant. It's not a pain medicine. It's a CNS acting medicine that suppresses brain function.

It was first developed as an anticonvulsant, and then people tried for pain. And if you talk to anyone who's on it, when I was a diabetes doctor at Mass General, I prescribed a lot of people with diabetic peripheral neuropathy. No one stayed on it 'cause they'd come in and say, "I don't feel good." You know what I'm saying?

T he point of a pain medicine is not just to change a number on a scale, which it seems like sometimes when I listen to people is what they think. It's actually to make the patient feel better, and part of the patient feeling better is how they feel on the medicine. So since our medicine has no CNS acting effects predicted and has none seen across six different clinical trials, I think that the answer to the question is it has a totally different and unique mechanism of action, never seen before.

The last thing I'll say is, there is a precedent for how much pain relief we ultimately should be able to get by blocking certain channels. Not saying VX-548 is there yet. Has anyone in the room ever had dental work and had lidocaine or Novocain? Do you know what that drug is?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Uh-huh.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

It's a sodium channel blocker. It blocks pain by blocking these sodium channels.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

That's the ceiling that you can go to. Why don't we use lidocaine and Novocain, like, take pills or inject ourselves? Because there's also sodium channels in your brain and your heart, not safe. So what we did was make a medicine that's 30,000-fold selective, that no one ever done before for the relevant pain channel, and so we can dose it up without any side effects. So that's why this is key. It's an entirely new era of pain control. Nothing, nothing ever like it has ever been out there.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

I think one of the most controversial aspects of the data, both among investors and among the physicians, is the lack of superiority against the opioid comparator. How does Vertex think about those data?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah. I mean, we've said it all along, so this is not a change in story because of the data. The problem with opioids is not that they don't work for pain. The problem is safety, tolerability, and addictive potential. So somehow people seem to believe, well, maybe they want to believe because they're prescribing it.

Actually, you should talk to patients rather than doctors, to be honest with you, as a doctor. Because, like, if you talk to doctors, they're happy writing the prescription, they send you home. Like, when my wife had her shoulder surgery last year at my hospital that I was at for 25 years, she had... And then her shoulder surgery is extremely painful, it lasts for, like, a year. She was sent home with four tablets from Mass General Hospital of opioids.

She didn't take any of them, which most people don't, 'cause they don't want to expose themselves to opioids, and she was in pain for months. That's reality. Do you know what I'm saying? So the reality is there's lots of undertreated pain, and even people who are given opioids, they're given 48 hours, but their pain lasts for weeks. You know what I'm saying?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Mm-hmm.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

T here's a great unmet need for a pain medicine that is safe and effective, that is more effective. Obviously, people will take and should take Tylenol and ibuprofen first. You can manage your pain with that, but then no one would be given opioids if that worked. So the question is, for all of you and for the doctors and for the governments, is do you want to force everyone to go through an opioid and only then try something else? Or do you want to try a non-opioid pain medicine and only use an opioid if that doesn't work? That's the key question.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

How do you convince the payers that they don't need to step through a generic opioid? Is there some way to-

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

... to convince them that, that that's the right strategy?

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Maybe you want to tell, just from a doctor's perspective, and then I'll-

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Cover the commercial.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

So I would say this, from a... Well, first, most important thing is a patient perspective.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

I would say pain is one of those things where I really would talk to patients. Like, go to someone who's post-surgical a week later, two weeks later, and ask them how happy they are, okay? 'Cause that's reality. The doctor, no offense, writes the prescription and sends you home. They're not with you in your house. They're not your spouse. Talk to someone who's a spouse or the partner or the child of someone who had surgery and ask how great is their pain control today.

But as a doctor today... You're encouraged strongly not to write prescriptions for opioids. You're told to give as few medicines as you can. In some states, you actually have to fill out multiple forms because they're tracking you because of the history of, you know, the abuse of opioids.

I think that, and then finally, from a payer, and Charlie, you can talk more about the government, there's a lot of interest at a high level in not having people take opioids, and that's because of the opioid crisis and all the deaths. One thing that doctors, again, I certainly don't mean sounding wrong. I mean, I love being a doctor.

I was a professor at Harvard Medical School for 25 years teaching medical students. But let's say the rate of opioid addiction is, like, 1%, which is people estimate. To a doctor writing prescriptions, that may seem low. How many people a year get those prescriptions for acute pain? 80 million. So even if it was 1 in 1,000, that would be 80,000. So I think people are just not thinking about this right.

For society, you don't want to put people on an opioid. But on the other hand, you know, an individual who's just looking right in front of their face might not see it, but I think payers do see it, I think hospitals see it, I think governments see it.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah, and there are many hospital systems with requirements to consider non-opioids ahead of opioids. The problem is there isn't anything effective. Eighteen states have legislation that require doctors to discuss non-opioid alternatives with patients before going to an opioid. Thirteen states have similar legislation in process.

At the federal level, just recently, bipartisan support for what's called the Alternatives to Pain Act, which is aimed at the Medicare population with three primary objectives. One, to prevent the requirement of step-through from an opioid to non-opioid. Two, to prevent the requirement for pre-authorization for a non-opioid, and three, to equalize co-pays for opioids and non-opioids. So I don't think, you know, it's much of a, an argument at all.

W hen you see that sort of response at the hospital system level, at the state level, at the federal level, I think people clearly understand the value of a non-opioid alternative.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

You referenced the mid-year filing. Can you give us a status on that filing and any what has to be done before it's completed, and what label do you think you'll ultimately get?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

As I said, our goal all along has been a moderate to severe acute pain broad label, and that's in contrast to a lot of medicines. They've gotten label like for knee surgery or for shoulder surgery or what have you. That's a much broader label. We worked with the FDA to design this trial. All the results are exactly what we sought. So we have to write the thing and send it in and answer any questions they have and do whatever they want to do, but I feel very confident based on the discussions with the FDA and the results we have.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

We'd expect to file in the middle of this year is the timing we're looking for.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Middle of the year. Perfect.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Go ahead, Eric.

Speaker 4

Yeah, sorry. Coming back to where we were just before. So do you actually see the majority of payers allowing the use of your drug ahead of the much cheaper generic alternatives?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Well, I would say this, if you ask me where I think we're heading as a society, do I think the first-line therapy should be an opioid or a non-opioid? I can't tell you exactly who will do what at what pace, but if you ask me, there's a lot of discussion about having a non-opioid before an opioid.

Speaker 4

Is this within the patent life of your drug or?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Our patent life is very long, but I don't mean in 20 years.

Speaker 4

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

I mean, near-term.

Speaker 4

Okay.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Here's the thing. I think there's lots of people who look at this, and they're looking for a precedent, but there is no precedent for being in this middle of an opioid crisis. It is a major societal issue with a new medication. I guess my question for you is, if you're a doctor, would you prescribe an opioid to someone?

Speaker 4

I'm not a doctor.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

No, I said if you were, would you prescribe an opioid to someone when you had a non-opioid alternative? And think about the risk you take if you do that.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Can you discuss the market size, both in terms of patient numbers and dollars, and I guess, working into that conversation, what type of premium price do you think you could get to the generics for, for a branded therapy?

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah, so maybe just start with, with acute and focus on the U.S. for the moment. You know, we've talked about the fact that 80 million people receive prescription for moderate to severe acute pain over the course of a year. The average course of treatment is about 2 weeks. That translates into 1.25 billion treatment days. Two-thirds of those days are prescribed or influenced in an institutional setting, so either a hospital or a surgical center or at the time of discharge. We've done work on density and concentration around the U.S. Eighty percent of that two-thirds is concentrated in 2,000 hospitals that roll up into 200 IDNs. Long way of saying, we've done our homework. We know what the coverage model looks like.

We believe that we can serve this with a specialty sales force. We will augment our sales efforts with digital and other approaches, and then, obviously, we're working to ensure that at the state and federal level, there's a strong tailwind for non-opioid alternatives. In terms of, you know, the market today, for acute pain, it's a $4 billion market at entirely generic pricing.

Given the numbers that I quoted around the number of treatment days, you really don't have to imagine much of a market share at branded pricing for this to be a multi-billion dollar opportunity for us, and that's just in acute pain alone. We haven't commented on pricing yet, so as we get closer to launch, that's something we can discuss.

Similarly, on the neuropathic side, 10 million people a year receive prescriptions. That translates into about 2.3 billion treatment days, so twice as many treatment days as the acute pain market. Again, you don't have to use much imagination to think about a multi-billion-dollar opportunity. So we're, you know, we do get a lot of questions around how big could it be, how small could it be, et cetera. Our view is that it's a multi-billion-dollar opportunity well within reach and something we can serve with our specialty sales model.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Turning to the diabetic neuropathic pain data that you released last year. I think one of the more controversial comments on the panel yesterday was how they framed the data versus how investors saw it. So investors looked at the data, said that you numerically beat Lyrica. That's impressive. It's also impressive that all three doses had approximately the same efficacy. The panel yesterday said you guys are looking at that all wrong. Sometimes Lyrica actually fails.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

How'd you pick this panel?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

George Teller.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

It would be. He, you know, threw open the phone book for a few guys about them. They, they said, this was unexpected. You guys are looking at it all wrong. Sometimes Lyrica fails.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Mm-hmm.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

How do you know that this isn't just all placebo in this trial? Could you-

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Sure.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Could you address that?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Multiple, multiple ways to look at that. So the first is that you'd have to say... I don't know who these people are, but you'd have to say that all four, that you had four, four such things because Lyrica looked exactly like Lyrica looks. So you have to say that was a false positive somehow. Then all three of our arms, which unfortunately the PK was such that they were overlapping and high, all had false positives. And then, while it's true that there have been in the hundreds of studies with Lyrica, some failures, if you look across at the results of Lyrica are exactly what we saw.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Mm-hmm.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

I don't know what they're talking about.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Okay, that's-

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

No, I'm serious. I don't understand it. Like, I mean, I guess if you notice, sometimes people look at one piece of data, they don't look at the context of the world. But you'd say then that Lyrica is a, is a placebo for the last 20 years, because the Lyrica results were exactly what's seen with Lyrica before.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Perfect.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Including the side effects.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Um-

Speaker 5

Phil, can I ask a question?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Sure.

Speaker 5

Thanks so much. I just wanted to follow up on his earlier question, that I think that convincing the docs based on legislation from the government, as well as just the opioid crisis, to write the script, your drug is easier, but it's to me, more of a cost issue for the insurers. I'm not saying that's right, but it's what it comes down to PBM coverage. So I'm wondering, have you engaged or will you be engaging the insurers about whatever the pricing is, if you can't tell us, and what's been their response, in order to get them to make you the right tier, not giving them, like, a 90% rebate to then give it to the client?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

The question is, is Vertex going to work with the payers, about the pricing?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah, the answer to that is, of course, you know, we haven't even filed yet, so there are limits on the conversations we can have regarding the profile of the medicine and pricing, et cetera. So, yes, but we... You know, the conversations that we can have at this point, we feel are very positive and constructive.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

In terms of the safety profile that you showed in the phase 2, can you discuss that in a bit, bit more detail, how it compared to Lyrica and how important is, is safety in long-term chronic therapy like this?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Yeah. So I think it's important to talk about safety and tolerability, because not that we're saying that like Lyrica is a medicine that's going to kill you. It's not. You know what I'm saying? I probably shouldn't have said that. We're not saying anything about Lyrica. What we're saying is, it has known side effects if you look at its label and you see them in our study, right? So you see the, the weight gain, you see the, the, the different side effects that are in there. We don't see any of them. So, in terms of the safety and tolerability, like, there's a positive control if you want in the study, which is you see the side effects that are on the label of Lyrica, and we don't see them.

Now, as a physician, here's a bit of data for you, forget my opinion. If you look at people with diabetic peripheral neuropathy, I think by the numbers, right, like 70% of them take two medicines. A high fraction take three medicines.

There's constant turnover in the medicines. If people were so happy with the medicine, why did they keep changing it? You know what I'm saying? And so I think that, but I think the reason is not so much the efficacy. Again, the key thing is you have to actually talk to the patients. People don't feel good on those medicines generally because of the CNS side effects, and it's not surprising because they're CNS depressants. Like, that's how they work. You know, it's not like you're saying, "Well, that's really weird.

Why would some-- like, if I wrap your ankle, why would you feel dizzy and..." It's because the medicines were used, because they're CNS depressants. They suppress, you know, action potentials broadly in the brain, in the case of that and in the case of, of, of opioids, they can, you know, they have these effects throughout the body. So that's-- to me, what's really striking is we've done 6 studies, you know, with VX-548. We also did 3 with VX-150.

The results of our studies are remarkably consistent. I remember people asking us a year ago or 6 months ago, "You know, mo-- everyone knows that psychiatric studies and pain studies, you often get, like, 2 out of 3. Would that be good for you? If you saw 2 out of 3, would you be happy?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Mm-hmm.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

We're 9 out of 9 at this point. The results are extreme, all highly statistically significant, including the three for VX-150. Multiple different pain types, always statistically significant, always similar size and effect, always clean safety, tolerability profile. That gives us great confidence. And I guess the question will be, you know, does society want such a medicine? And I guess, you know, I believe they will. And I think the other thing, you know, when people think about, payers and all that, just one thing you also... We don't have data on this, so I'm not suggesting we have data. But, you know, one of the things that does take time and money is people coming back because they're, like, not doing well.

Y ou have to also factor in how many patients come back to see the doctor again because they're in pain, or go to the emergency room because they're in pain. Because if you're able to or, you know, concerned about those things, you have to think more than just like the, you know. There's a total cost of the procedure, there's how much a branded pain medicine would be, and there's both how well you do in terms of all the other issues we were talking about and patient satisfaction, but also, like, do they just go home and do well or do they come back?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Maybe just one or two more questions on pain before moving to your nerve-based business. In terms of the path forward in neuropathic pain, you're talking about meeting with the FDA to design a pivotal trial this year, also starting a phase two in LSR. So, I guess first, what does the pivotal likely look like? And second, we've heard LSR is a tougher indication because it's part osteoarthritis or it can be part peripheral neuropathic pain. Does that have to succeed? Is that on the critical path, or can you just get a label on DPN?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

A few different questions there. So the first, I'll go, what's our goal? And then I'll talk about LSR, and then I'll talk about DPN.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Perfect.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

With regard to our goal, our goal is a broad PNP label, a broad peripheral neuropathic pain label, and we have not yet had that discussion with the FDA. That's the discussion we're gonna have.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Does anyone have that label?

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

No.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Lyrica is just DPN.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Not in America. Not in America.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Got it.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

There's also no approved medicine for LSR. Okay? So the goal is that, and when we met with them about acute pain, we came up with this study design with them, which was one study in bunionectomy, one study in abdominoplasty, and this 250-person study. That's the discussion we want to have with them. You know, I'll just jump to, what if LSR doesn't work? What if we can't do that? Yes, we could, of course, just do a pivotal trial and just try and get a label in DPN. But our goal is to get the broad label.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Because it's like 20% of people are DPN with PNP, 40% are LSR, and the other 40% are a wide variety of things.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

I f we can get all of that in one label, that's our goal. Now, with regard to LSR, LSR is not osteoarthritis, but if you start with back pain, you're gonna have both. So this is the mistake. If you say back pain, I have lower back pain, that could be everything from a strained muscle or tendon to some sort of osteoarthritis to LSR, which is, if you could hold my coffee for me. You have a hole in your spine. The nerve goes through it, okay? It gets pinched somehow. That's LSR, okay? And it's a pure neuropathic disease because the nerve is firing. It doesn't hurt the person. That's not osteoarthritis.

Now, if you just take someone, thank you, who has lower back pain, you're gonna have a mess.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

If you look at other studies people have done, they've tried to treat lower back pain.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

That's been the confusion.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

But that's not what we're doing.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

In order to get into our trial, you have to have a clinically clear LSR. What does that look like? The distribution of pain when you have one of these pinched nerves is wherever that nerve goes. And for example, sciatica, which is the most common form, which some of you may have had or known about, is a very funny distribution. So if someone walks into your office as a doctor, they say, "I have this weird pain I got acutely. It's on one side of my body.

It's sort of my butt. It's the back of my leg. It goes to the side of my calf and into my toes." That's sciatica. There's nothing else that does that because that's the travel of the nerve. That's sciatica. That's the only way you get into our trial. That's not osteoarthritis.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Yeah.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

The osteoarthritis might have been involved in why the nerve is pinched, but that's not the pain, because the pain, if you have, like, spinal or a tendon or muscle, is back here. So it's actually very easy if you design the study for LSR. It's hard if you try and interpret LSR from lower back pain.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Got it. Okay. I do want to touch on a few other aspects of the business.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

I'll take a question.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Sure. Go ahead.

Speaker 6

Just a quick question. The strategy as it relates to commercial, global commercialization of the opportunity. So is this something that you're going to bring to not just Europe or other regions of the world, but developing regions of the world, low, middle countries? And if so, how are you thinking about that strategy pricing?

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Question is about global commercialization of the pain program.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah, the short answer is we're focused on the U.S. right now for acute pain. We think that there is a huge opportunity there. We would like to demonstrate the value in the U.S., and then we'll talk about the rest of the world at some other time.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Maybe a few questions on the base business. Your guidance this year assumes 8% growth at the midpoint. What are the pushes and pulls in guidance? Could there be upside? Are there risks to hitting that?

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah. So the guidance for total product revenue, which includes both the CF portfolio and Casgevy, is $10.55 billion-$10.75 billion, 8% at the midpoint, you're right. Another really strong year. Importantly, that's roughly $800 million of incremental revenue over last year. So very significant at this scale. You know, we feel confident about it within... You know, in the CF, we're gonna be treating more patients.

The growth drivers in CF are, you know, patients who initiated medicine last year, annualizing. We're continuing the rollout in the younger age group in 2 to 5. We are working on reimbursements. There are a handful of, you know, smaller countries where we don't have reimbursements.

O f course, we're preparing for future growth by continuing to pursue an mRNA therapy for those 5,000 patients who don't benefit from CFTR modulators today. And then, of course, we've got Vanza, which could help us address the roughly 6,000 patients or so who've discontinued one of our medicines for one reason or another.

S trong growth year for CF, strong growth into the future, and I guess importantly, we did recently raise our estimate of the number of patients with CF in North America, Europe, and Australia to 92,000. Roughly 20,000 of those weren't on our medicine, one of our medicines as of the beginning of the year. So significant opportunity for growth in CF in 2024 and beyond.

T hen, of course, Casgevy, as I mentioned, will contribute to revenue this year and kick off that era of diversification for us there. We've commented that we are incredibly excited about the opportunity. We see Casgevy as a multibillion-dollar product over time. This first year, we're working on getting the launch right. The patient journey is long.

There are multiple stages and multiple months in the patient journey, so it will be a gradual build over the course of the year, and we look forward to updating people with a few metrics, notably our progress on authorized treatment centers. We don't see that as a rate limiter. We're targeting 50 treatment centers in the U.S., 25 in Europe. We have, to date, activated 12 in the U.S., 3 in Europe, and 1 in the Middle East.

That's going very quickly now, so we don't see that as a rate limiter. You know, overall, we feel very confident about the year, and we'll, you know, update at future quarters as we go.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Maybe one last question. We're just about out of time. In terms of, cystic fibrosis, I think the number one question we get from investors is how quickly will the transition to the Vanza triple go? What are Vertex's thoughts on, on the rate that you'll switch people, specifically the switches from Trikafta onto, onto Vanza?

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Yeah, and, and the answer is to be determined. You know, Trikafta is a fantastic medicine. We saw with the launch of Trikafta that the switching from previous generations of medicines or Orkambi Symdeko was instantaneous and complete pretty much. But Trikafta is a fantastic medicine, and a lot of people are deriving significant benefit from it.

That said, we think Vanz is a better medicine, and we look forward to educating patients and doctors around the benefits, and, and, we know that we can get more patients to carrier levels, and we think that that is a really exciting opportunity. It's gonna be compelling, especially for younger patients. So we've not commented on the rate of switching at this point. I guess importantly, we're not gonna look to drive it per se.

All of the switching that's happened with our previous medicines, and we would expect the case with Vanza, is really patient and physician-driven, and we're here to support that.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

So one quick statistic-

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Sure.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

95% of the people on Vanza in this trial had a sweat chloride below the diagnostic threshold. So the way you get diagnosed with this disease is you show up with symptoms, you have your sweat chloride measured. 95%, that's in the 6-11 group. If you're a parent and you're making this decision, why would you put yourself, your kid on a medicine that has you, like, you know, with a level that's above that as opposed to below that? So that's just an example. Other people were happy and comfortable, will have to decide.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Mm-hmm.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Some people have stopped or whatever, but I think that's an important statistic in terms of what would you do as a parent.

Phil Nadeau
Managing Director and Senior Biotechnology Research Analyst, TD Cowen

Makes sense. With that, I think we're out of time. Thanks for interesting discussion.

David Altshuler
Executive Vice President and Chief Scientific Officer, Vertex Pharmaceuticals

Thank you.

Charles Wagner
Executive Vice President and Chief Financial Officer, Vertex Pharmaceuticals

Thanks, Phil.

Powered by