Welcome to day one of the Jefferies London Healthcare Conference. My name is Dennis Ding, biotech analyst at Jefferies, and I have the pleasure here of having Amicus Therapeutics with us. We have Simon Harford, CFO, and Sébastien Martel, COO, here with us. So maybe to kind of kick things off, just to level set us for those in the room who may or may not be familiar with Amicus, just give us a little bit of the background, what you guys are hoping to tackle and hoping to solve.
Sure. So Amicus was founded just about 20 years ago. We have two drugs that are both being commercialized currently. One is Galafold for Fabry disease, which in the third quarter of this year was growing extremely strongly at about sort of 19% on a constant exchange rate basis year on year. That is a growing market opportunity for us. It's a market that started off with about 10,000 diagnosed patients back when we launched sort of seven or eight years ago, is now about 17,000 diagnosed patients, and not all of those are treated. So we continue to see very strong growth. In fact, this year and last year, the strongest growth since the first year of launch.
Secondly, we have Pombiliti and Opfolda, which was approved in both the U.S., the European Union, and the U.K. in 2023. So it's been on the market for just over a year. That drug continued to do well with just over $21 million worth of sales in Q3 and is launched in the U.S., Germany, Austria, Spain, and the U.K. as the major markets. We will continue to launch in other markets outside of the U.S. as we get pricing and reimbursement in the coming months. That is the second big driver of our business. As we look at that drug, we raised our guidance actually for Pombiliti and Opfolda from $62 million-$67 million for this year to $69 million-$71 million due to the strength of performance in the sort of recent months as well as our projections going forward.
We then, from a point of view of commitments to profitability, having been in existence for 20 years, it was our desire two years ago when our CEO, Bradley Campbell, came in to turn a profit on the company. We committed this year to being non-GAAP profitable for the full year. In fact, as of September, we were already about $45 million into non-GAAP profitability. So we've been able to do that basically by leveraging sort of 30-plus% growth on the top line with pretty nominal operating expense growth. And so most of that's falling to the bottom line at this stage. So that's where we are currently. I'll hand it back to you.
Yeah, perfect. So it sounds like Galafold, which has been on the market for many years, still continuing to grow meaningfully, right? You have Pompe, supposedly another growth driver, and you guys are going to be profitable. I think all that is very exciting. I think a lot of investors after your third quarter and maybe also recap briefly just your thoughts around Q3, a lot of investors have been focusing on Pompe, the new guidance that you guys delivered, and just kind of some questions around the trajectory of Pompe moving forward in terms of new patient adds, and I think also importantly, the outlook into 2025. Do you think you can comment a little bit on all of that?
Yeah. So what I would just say is, I think as you look at the company overall, the two value growth drivers currently, we can get to the topic and maybe business development and stuff for pipeline afterwards. But I think for what we have today, value is going to come from two things. One is Galafold. The focus is clearly of investors on Pombiliti Opfolda because we're only a year into the launch. But the reality is, if the growth rates on Galafold continue, at similar rates to what they are today, combine that with the fact that we settled with Teva from a patent perspective, so no patent would come in until January of 2037, which is another 12-odd years away, there is huge value still to be created in that fast-growing market. The focus at the moment is obviously much more on Pombiliti Opfolda.
That is also an important driver of value because essentially what you are doing is we built the infrastructure for Galafold. We're now leveraging with the same sales force, the same teams, customers in the Pombiliti Opfolda Pompe space. So really, once you get through the launch phase, basically again, stuff is dropping to the bottom line from a profit perspective because the infrastructure is already in place. But maybe you can talk a little bit about Pombiliti Opfolda.
Yeah, Dennis. So we're very pleased with the way the launch has been going for Pombiliti and Opfolda. Last year was a turning point for us to get this product approved in the U.S., in the U.K., and in Europe more broadly. Last year, we achieved $5 million of sales within a few months, sorry, $11 million of sales in a few months. First quarter, we had 11, second quarter, 16, third quarter, 21. We raised guidance on the back of good results in Q2 and Q3. The characteristics of the Pompe market are such that this is a healthy growing market. If you look at sales reported by Sanofi at our own sales performance, you get to a growth rate of mid-teens roughly. Last year, this was a $1.3 billion market. So a sizable and growing market. Our strategy at this point in time is very much focused on switching patients.
We're seeing significant uptake, in particular in markets where we've been the longest. There is one market that I'd like to point out, the U.K., where we got a chance to have Pombiliti and Opfolda available before actual approval by MHRA, thanks to the EAMS program. In effect, as we speak, we've been in the U.K. market for now three and a half years with Pombiliti and Opfolda. Recently, we reached 35% market share in that LOPD market. Hopefully, if we can repeat that in other markets where we've launched, we'll be very pleased taking that kind of share in that market.
Okay, perfect. And as you think about launching into Pompe, what do you think the revenue growth trajectory would look like moving forward? Do you expect some sort of acceleration in terms of new patient adds, or is it a kind of steady, gradual, progressive type of launch trajectory that you guys are thinking about?
Yeah. So as we speak, as Simon alluded to, we're only launched in five markets, soon six markets with the recent pricing and reimbursement obtained in Czech Republic. We have another eight active ongoing discussions for pricing and reimbursement, which should see us launching in some additional markets in the next six to nine months. So that geographic expansion will play a significant role as we move into 2025. We're also in a situation where in the U.S., because Nexviazyme was launched a couple of years before we were introduced, 2025 will see a number of patients getting to that one and a half to two years on therapy on Nexviazyme. And that's where the majority of Pompe patients are in the U.S. So we foresee that a number of patients will start observing a decline in their disease. And from what we've seen so far, that's a trigger for physicians to consider switching and moving to an alternative like Pombiliti Opfolda. So potentially more switchers in the U.S., expansion in Europe, while also continued penetration in the markets where we're already launched.
So you talked about eight additional launches over the next six to nine months, that type of timeframe. Are there any kind of new launches that could happen by the end of this year or U.S.?
No, and in some way, that's also what we indicated when we talked about full year guidance. We don't expect a new launch in the fourth quarter. We may see actually some positive pricing and reimbursement within that timeframe, but we're just a few weeks away from the end of year, so we wouldn't have a massive impact in terms of revenue, but again, we could see a number of those markets gain reimbursement before end of year.
Can you talk a little bit more about the switch dynamic from Sanofi's drug? When a patient with Pompe who's on Lumizyme or Myozyme goes to a doctor, can you talk a little bit about what that kind of discussion looks like and where Pombiliti kind of comes into the conversation and when a logical time point would be for that switch to take place?
Yeah. So that's where the efforts of our medical and commercial teams is crucial. On one hand, in continuing to educate physicians around the disease, the fact that there is a treatment now available that has shown to provide an improvement versus Myozyme, and that's a claim that we have, for example, in the U.S., so that in some way, stability shouldn't be the standard expectation. So challenging physicians through ad boards, symposia, the regular interactions they have with our medical teams, that obviously those who are declining are prime patients for potential switch. But we also think that the vast majority of patients, maybe around 50% at any given time, that are somewhat stable or perceived to be stable may actually not be.
So having those discussions around the criteria that physicians use to evaluate patients, and they usually do every six months, sometimes every year, which also causes a little bit of a lag, is super important. Besides the follow-up of patients, the way to evaluate them on a regular basis, listening to them also quite a bit. Patients don't talk in FVC or six-minute walk test. But they may share a number of things that are hindering them in their day-to-day life that could actually signal that they're declining. And then the other key thing that we've got to continue doing is ensure that we, to the best of our ability, differentiate our product in the best possible way. We're not just an ERT. We are a combination therapy that comes with an enzyme stabilizer. There's a good reason for that.
Our ERT itself is also quite differentiated from our competitors. Continuing to talk about that will also be key. From the market research we're doing, we usually ask physicians to project themselves, where do you see yourself prescribing this product or that product in a year from now, in two years from now? We don't hear a lot of pushback, essentially. Many saying it is just a matter of time before we continue to see, again, Pombiliti and Opfolda getting a sizable share of that Pompe market.
What do you think is the level of awareness among physicians around Pombiliti? And how familiar are they with the profile of the drug, with what you mentioned like six-minute walk and other kind of biomarkers and things like that. But I'm just trying to gauge, if a patient comes in, says, "Hey, doc, I'm not doing so well. I can't climb up the stairs or whatever," how quickly can they identify that and associate Pombiliti with that kind of identification, right?
Yeah. So I think they're pretty well aware. This is a market driven by specialist physicians who've, for most of them, have been using our company's products for quite some time. Like most rare diseases, this is still, unfortunately, significantly underdiagnosed. I'm always astonished to see the patient journey that sometimes it takes six, seven years for a patient to get to a proper diagnosis. I was at one of our partners' manufacturing site recently with a patient testimonial, and she shared her story, and it took her seven years before she got a proper diagnosis. She was diagnosed with two other rare diseases, which were wrong diagnoses before she got to that diagnosis of Pompe, and being on treatment has literally changed her life, so I think that they are well aware of Pombiliti and Opfolda. When it comes to switches, different stories here.
In the U.S., where Nexviazyme had a significant head start, we're seeing more patients, about 60% of them are actually on Nexviazyme versus 40% on Myozyme. Interestingly, over the last three quarters, that ratio of Nexviazyme to Myozyme in the U.S. has actually been flat. It's been 59% Q1, Q2, Q3. In some way, our launch into that market has kind of stalled the relative share of Myozyme versus Nexviazyme. And not surprisingly, two-thirds of our switches come from Nexviazyme. In Europe, where Nexviazyme was introduced later, actually in Spain, as an example, we were introduced at the exact same time, we're neck and neck. So our market share in Spain right now is 18%, and Nexviazyme has also 18%. And the majority of switches we're getting, surprise, surprise, are coming from Myozyme because Myozyme still has 60%-61% of Sanofi sales in those markets.
Can you talk a little bit about persistence on Pombiliti, given that it's been a year, a year and a half into the launch? Are patients starting to think about discontinuing or switching back to Nexviazyme? Is that kind of dynamic that you guys may be starting to see as well?
No, not really. Again, it's early days. We've been launched in those markets for maybe with the exception of the U.K., where, again, we continue to grow our share. So there's been very small numbers of discontinuations to date.
Okay, got it. And how many patients? Because I think there's around 1,000 patients on Sanofi's drugs in the U.S. for Pompe. Do you think that's kind of like the right ballpark?
I'd say 800-ish.
800-ish. So as we go into next year, let's say 25% of them are worsening. Would you say that's kind of like the pool of patients that you guys would be focused on targeting at first?
Yeah, those are the most likely patients that will be potentially switched to Pombiliti. We're also outside of the U.S. getting our fair share of naive patients. Actually, in the U.K., I think we're getting most naive patients as we speak. Now, having said that, the contribution of naive to the overall business dimension is rather small. I think on a global basis, you can count on about 200-ish new Pompe patients being diagnosed on a yearly basis worldwide. So that's a relatively small number. If you just look at the U.S., you're talking about less than 50 patients naive per year.
Okay. Can we switch over to Fabry for a little bit?
Mm-hmm.
So talk about the dynamics with Galafold and some of the progress you guys are making, capturing some of the naive patients, identifying them. Can you kind of update us on the progress around that?
Yeah. So compared to the Pompe market, the Fabry market is yet again a sizable rare disease market, bigger than Pompe. So last year, this was roughly $2 billion market. We continue to be excited by the fact that essentially all our growth is coming from demand, so not supported by price. Price is essentially on a global basis, neutral, slight increase in the U.S., slight decrease ex-U.S. We're also pleased to see that the overall Fabry market is healthy. If you look at our competitors, Sanofi, Takeda, Chiesi, and ourselves, you put it all together, and you're into the high single-digit growth rate. So what's driving that? Clearly, if I go back 10 years ago, the way Fabry was looked at, this was an X-linked genetic disease, classic Fabry disease, mostly male. But over time, the practice of physicians has changed.
They've realized that women carriers were also suffering from Fabry disease, also had symptoms, and sometimes very significant clinical symptoms. That led them to take a different look at females with Fabry disease. We're seeing a growing proportion of our business coming from females with Fabry disease. We're also seeing trends of earlier treatment for Fabry disease. For quite some time, the usual rule of thumb was until you have symptoms, don't bother much. This is gradually changing. Also, imaging techniques have helped here. There's, again, a willingness to treat disease earlier. Clearly, because it's an X-linked disease, you've got that unique opportunity that when a patient is identified with Fabry disease, you can run family tree mapping, and as a result, end up identifying four or five patients within the family. There's kind of a multiplier effect also in your diagnosis efforts.
That's, again, helping sustain the overall growth rate. Last thing, more precisely for Galafold, is we continue to grow our share. As you well know, Dennis, we're only indicated for those Fabry patients with amenable mutations. So that's a subset of 35%-50% of Fabry patients, depending on the market and the prevalence of some of these mutations. So, for example, in the U.K., that's closer to 50%. In other markets, it may be closer to 35%, again, depending on the mix of mutations you have in a given country. So we grow our share within the amenable pool of patients. At this stage, I think six years into the U.S. launch and eight years into the European launch or Japanese launch, we can say that we've established Galafold as the standard of care for newly diagnosed amenable patients.
We think that we are getting a very high market share of new Fabry patients diagnosed with amenable mutations. The fact that the drug is an oral therapy also makes a big change for someone not being too sure about going on a biweekly infusion that I think helps a great deal. There are still markets where we've launched more recently where we continue to see some switches, patients moving from ERT to oral therapy. The big chunk of our growth is really coming from naive. The key thing, maybe as a conclusion here on Galafold, is we're, again, six years of launch in the U.S., eight years ex-U.S. On a year-to-date basis, we're growing at 18%. We sustain a very strong growth rate. As you said earlier, Simon, we also have a long runway ahead of us with the recent settlement. It actually tells us that we have more years to come than the years we've been on the U.S. market with Galafold.
Right. And maybe I think in the last minute or two, can you just discuss a little bit about gene therapy, some of the updates out there from a competitor who got a positive FDA meeting, could file second half of 2025? Just talk about that dynamic and where you expect adoption from gene therapy relative to Galafold.
Yeah. So I just mentioned that Galafold was an oral therapy. You put an oral therapy vis-à-vis a gene therapy, that's a big decision for a patient to make to embark onto something that should in some way provide a treatment for a number of years. I won't go into all the question marks that people have around durability, manufacturability, cost, and so on and so forth. I would just say that from what we've observed is that gene therapy has been most successful commercially in diseases where kids are impacted early on, and it's a matter of life or death if you're not on that therapy. So think of SMA, think about DMD. There's been significant impact from gene therapy in those fields. Fabry is not exactly that kind of disease. I would say that take a look at hemophilia also, where you've had recombinant replacement factors for many years and other new therapies. It has been commercially a very challenging proposition, and so we don't expect Galafold to be impacted here.
Okay. Perfect. Well, I think that's all the time that we have today. Thank you guys so much for hanging out with us, and have a great conference.
Thank you.