Hi everyone, thank you for joining us today for the Amicus Therapeutics fireside chat. I'm covering analyst Ritu Baral, and joining us from Amicus is CEO Bradley Campbell. Brad, thank you for joining us today. We're going to kick off with your Pombiliti launch, the Pombiliti + Opfolda launch, which I think is the main point of investor focus. You launched Pombiliti in the E.U. and U.K. midyear last year, and in the U.S., in the fourth quarter after finally getting your inspection, you already reported—that was—that's a story. You already reported $11.6 million from launch in full year last year, about 120 patients on commercial drug as of January.
Can you remind us of the 105 EAP patients that you indicated have gone from EAP to commercial? Does that represent all of the EAP patients in the approved geographies, or could there be more near-term tailwinds on the 120 patients?
Sure. First of all, thanks, Ritu. Thanks to TD Cowen for having us here. Thanks all of you for joining us, and your team as well. So maybe before we dive into the launch, I can just start framing it.
Sure, absolutely.
Just at a high level. Hopefully most people know who we are and what we're about, but I think this year is going to represent a really significant pivot point in the trajectory of the company. We have three core drivers of value for the company. First and foremost, Galafold, of course, which I know we'll talk a little bit about, which is our initial commercial product. It's a small molecule chaperone for the treatment of Fabry disease. Galafold did $388 million in global sales last year, and that was about 17.5% to 18% growth on a constant currency basis. This year we're guiding to 11% to 16%. So it is a significant product. Continue to see a lot of room to continue to grow that product over time and really serves as the core of our value today.
Of course, Pombiliti Opfolda, our new, two-component therapy for Pompe disease, which I know we'll dive into and talk a lot more about, newly approved product at the end of last year, launching, seeing great progress with that product. We think that could be a $750 million to $1 billion product opportunity at peak, so a really important part of our future. All of that is supported by a very strong financial position. I think very importantly, and maybe relatively unusually for a company of our size, we turned the corner, fourth quarter of last year to non-GAAP profitability, and this year we're committed to a full year of non-GAAP.
That was on Galafold alone.
Exactly, yeah.
That was on Galafold.
Yeah, to your point, there was, you know, small small.
Pomb/Op is really that next leg of revenue growth.
Exactly right. I think that's the beauty of the story of Amicus, is what we've built, to support, Galafold is already a profitable business, and now you lay on, the future of Pombiliti Opfolda, plus the continued growth in the Fabry franchise, and, and we think this is a really exciting story for years to come.
Tailwinds on the 120.
So back here. Yeah, so just the way that number breaks out, so remember it was 120 patients who were either on drug or scheduled to start drug as of J.P. Morgan this year in January. 105 of those were from existing clinical trial or expanded access patients in the U.K., Germany, and the United States. The balance was new commercial patients, which we can talk more about because I think that's an important segment.
We had, going into the launch, about 200 total clinical trial patients in all geographies. In the remaining U.K., Germany, U.S., there are actually a handful of pediatric patients in our ongoing pediatric LOPD studies and then IOPD studies for patients with infantile onset disease. Those patients we think would start to, you know, read out from a data perspective later this year and into next year, and you could see us expanding into pediatric labels, I would say, kind of in 2025 and beyond.
That 105 represents everybody currently covered by the label.
LOP, exactly right. Exactly right. If you think about the balance of the 200, there are about 40 more patients throughout Europe. And so you as we launch into those markets, you'll see those patients convert over, and then the remaining 55 or so are in countries like Japan, Australia, Canada, which, again, you'll start to see us have approvals and launches in kind of 2025, 2026 timeframe.
Got it. Okay, so that was the 40 to 50, and then 40 more in the 40 to 50 in Australia, Japan, and Canada, and 40 more in the EU, and those are geographies that you plan to submit either pricing applications, dossiers, or actual approval applications in the next year?
Correct. Yes.
So that, that sort of 80 to 90 is in your crosshairs for the next 12 months. Is that fair?
I would say 12 to 24 months.
12 to 24 months as a tailwind on the 120 that you have right now.
Correct.
Just from those. Just from the clinical trials. Okay.
Exactly. Yep.
Then let's get into what you're seeing as far as the new commercial patients, of which 15+ right now. Can you describe them as far as switch? What are they switching from, and are you getting naives already?
Yeah, so we, on the call, we provided color not just on those 15, but then, of course, since then we put on more commercial patients, and so kind of broad trends that we're seeing over the first, call it, five or six months of launch in each of those markets. So the first, and I think maybe the most important piece, is that in the United States in particular, where you have a majority of patients, probably two-thirds of patients, have now switched over from the original product Lumizyme to the new standard product Nexviazyme, we're seeing about two-thirds of our new commercial patients switching from Nexviazyme. And so one of the questions I think that we had gotten, which I think is a natural question, which is, well, if a patient were to switch from Lumizyme to Nexviazyme, are they sort of lost to Pombiliti Opfolda?
When might you be able to start to switch those patients? And what we're seeing, of course, it's relatively early days, but I think we're seeing enough data right now that says, no, in fact, we're switching both Nexviazyme and Lumizyme patients, and in a market like the U.S., which is probably the only one, where a majority of the patients are now Nexviazyme, that's where we're switching a majority of our patients. I think that fundamentally comes back to the point that we've made, which is, from a physician's perspective, it's not what drug are they on, it's how are they doing. And if they're not doing well or not meeting my expectations, then I'm looking for an opportunity for them to do better.
Let's talk about the definition of that. Your label says LOPD patients not improving.
Correct.
So our checks and the conversation on your call suggested that our checks at the Lysosomal Storage Disease Conference suggest that it's really limited right now to what the doctors describe as decliners. And I started bugging you about this at World, but, you know, Genzyme has one definition of decliner, and you have another definition of decliner. So could you, because they'll say, like, if you're declining on six-minute walk, you may not really be declining, you may just not be trying. Can you talk about what, who you're seeing, who the decliners are? What defines the decliners that have switched?
Sure. Yeah, so I'll leave that, that comment. I'll let them comment on their own definition of decline. But from our perspective, I think it's fairly obvious, right? So I think what we've seen through our market research, the market research we did leading into launch was, if you ask physicians sort of what do their patients look like, about a quarter of them are still in some sort of improvement phase, which I think you, you see if you look at the data between the products that are out there. About a quarter of them are in a clear defined or clear decline phase, usually measured by things like six-minute walk, but, and then maybe 50% or so are in the kind of stable middle.
You know, I think absent a new therapy and Nexviazyme only launched two years ago, I think that makes sense that physicians would say, "Yeah, most of my patients are stable," and that's really all that they could expect out of a therapy is stability. If you have to ask a patient, "What do you want out of your therapy?" it's, "Gosh, if I could just not lose the ability to walk," or, "If I can just, you know, not go on to permanent ventilation or just keep the function I have," that's really what they would want. I think what's exciting about the data we've shown and the label that we now have, you know, we believe we have the ability to change the outcomes for patients and that they can change their expectations for therapy.
So the first conversation, and the one that you're getting at, is, "Let's talk about that definition of stability or decline." I think it's obvious if a patient is declining, you know, a physician's going to want to switch, and I think that's an obvious first target for us. And I agree with you, probably the majority of the patients we've taken have been declining on six-minute walk.
Declining on six-minute walk.
Yeah, on some sort of clear outcome. Where I think what's most exciting for me and what having any new therapy allows now for the first time in decades, a conversation that says, "Well, let's really look at that stable middle. Are they really stable? Honestly, I've had this conversation with multiple physicians, and you can just even, you know, see them kind of working through this. Okay, well, they seem to be stable. Well, let me ask them more carefully. Maybe they're having a harder time walking up the stairs, or they're using more ventilation. Maybe they only had to use ventilation for a part of the day, and now they're using it sort of BiPAP, CPAP for a larger portion of the day, you know, maybe.
Sleep was something that they should.
Sleep was a huge one that is that.
Posters.
Yeah, and that was one that we hadn't appreciated as much for Pompe disease. It could be because of muscle fatigue, but it could also be because of, many times they have sleep-disordered breathing because of lack of oxygen at night because their sleep is impaired.
The CPAP therapy.
Exactly. So it may be sort of a sleep-related fatigue as well. But in any event, I think that's the conversation that we're driving with physicians now. And what we're finding is that actually that stable middle is probably made up of more patients who are in some sort of decline and therefore should switch to a better therapy if there is one. The way you win in the end, though, of course, is you establish Pombiliti + Opfolda as the best therapy, and then any patient who's not improving should be switched, right? They should reestablish a new baseline or, better yet, prevent the decline in the first place. So to me, that's the ultimate outcome. That's what we're hoping to drive to. We're still in the, you know, early part of that journey today.
So I'm going to go off-script for a second because you bring up an important point. How often, first of all, how often are these Pompe patients seeing their geneticists or their neuromuscular experts, and how long is that appointment such that the expert can assess six-minute walk, assess FVC, really have a conversation with the patient about their fatigue levels and their life in general because if they only have, like, 30 seconds, none of that's coming out?
Yeah. What we understand is that patients are seeing a specialist. Oftentimes a geneticist could be a neuromuscular specialist, neurologist, etc., but they're seeing their Pompe specialist once every six months or once every year.
Okay.
Right? And so usually in those visits, they're going to go through a comprehensive workup. They may not always do six-minute walk. They could do other things. There's something called Gowers' sign. There's Timed Up and Go . There's walking up and down stairs. But they will do a comprehensive Pompe workup, and the doctors spend a good amount of time with them. In between, unless they're in a health crisis, a pneumonia or something else that would put them into the emergency room, the only healthcare provider they're seeing is probably they're either getting infused at home, so there's a home health nurse. They might be going to an infusion clinic, although then again, it's usually typically a nurse that's doing the infusions as well. So they're really only getting worked up about once every six months or once a year.
I think in the U.S., in an ironic way, because Nexviazyme launched, you know, more than 2 years ago, that tells you that those patients have been on therapy long enough so that their physician could do a workup and therefore have some sense for how they're progressing in their disease, which I think then provides an opportunity for us to have a switch conversation.
So what is what is that conversation? What are the terms in the detail that you are talking to and your salesforce is talking to the doctors about? Gowers' sign was mentioned, again at WORLD Symposium. Fatigue was mentioned at WORLD Symposium. Assist devices. What are you specifically asking them to think about beyond six-minute walk, beyond FVC? To get this going in their heads?
So, you know, obviously it's an on-label conversation, and so what we're limited to is what we think is very compelling data, and we should remind the audience, for those of you who, you know, who have forgotten or haven't paid as much attention, what's remarkable about this product and what's in the label is that in patients who were on enzyme replacement therapy for five years or more saw an improvement in 6-minute walk and a stabilization of forced vital capacity. So this is the only product that's been studied in a controlled setting that has showed that patients on enzyme replacement therapy switch to our therapy and see an improvement in their outcomes.
And so that is really the commercial discussion, but what's important is as we get into publications, we saw some of this at the WORLD Symposium conference, as more and more of this data gets out there by word of mouth, etc., it's also the growing body of real-world evidence that you can do from a medical affairs perspective, from a medical education perspective, and I think that's what gets into those how is the patient feeling, patient-reported outcomes, etc. If you look at the data that we've published on in the phase III , it shows, you know, quite good outcomes in those parameters, but clearly the sales reps are focused on what's contained within the label.
But I think really importantly, it is for patients not improving on ERT. To me, I think our core visual aid says, "Improvement is possible." Just that whole concept that you can improve outcomes in patients is, I think, an incredibly powerful, commercial positioning.
Within the phase III protocol, did you generate or did you keep track of sort of assistive devices needed, whether it was ambulation or, or lung function, or did you track Gowers', or is that sort of an ongoing thing?
So we did track a whole host of secondary outcomes. As I think about it, we did not track mobility assistance as an example, although effectively if somebody had to use, let's say, a cane to do their six-minute walk, then you kept that standardized throughout the protocol. Obviously if they weren't able to perform the six-minute walk test, then they weren't included in the study. So they had to be mobile to some degree, and you generally kept their assistance consistent through the course of the study. But yes, and I would encourage folks to look at the phase III publications. Of course, we can share them with you if you can't track them down, that show the impact we've had on all the other measures of disease, which I think are also compelling and significant.
Got it. What is the breakout between decliners or stable and or switches and naive right now? Snapshot in time without, you know. Giving us updated necessary. I'd love updated numbers if you can give it to us.
Nice try.
Yeah. I am your favorite.
I can tell you, of course you are. So, you are tied for first with all of our analysts. So just in case somebody else is listening. So, yes, so in the United States I've already talked about it. It is about two-thirds Nexviazyme, one-third Lumizyme. What's great, though, is outside the United States where Nexviazyme launched, you know, more recently and has a lower share, we have about equal distribution of Lumizyme, naive, and Nexviazyme patients. And probably a majority, actually, Lumizyme and naive patients because they're the larger prevalent pool of patients. So what we take by that is it's not just, you know, we're switching the decliners in, in those two treated populations. We're also getting a nice stream of naive patients coming on board, which tells me that those physicians believe, you know, this is the best therapy to start their patients on.
And that sort of addresses some of the messaging that we've gotten from KOLs, which is, "Oh, we really like this. It might be the strongest. We'd like to save it for third line," which of course is the kiss of death for something like antibiotics. In this case, there's an inevitability to decline, but, you know, how do you accept or address that messaging?
I think you're right. I think the naive uptake to me tells you that that's not the case. Does part of me feel like, "Okay, fine, if that's the reality and this is a progressive disease and everybody ends up on Pombiliti Opfolda, is that a bad thing?" Well, no, but I agree with you. It does suggest that there's some kind of step-through process, and I don't think that's what we're seeing. I think what we're seeing is different markets have been impacted by the launch of the second-generation product in different ways, meaning when did it launch? In the U.S., it launched sooner, so there are a lot more Nexviazyme patients. In Europe, it launched later, so there are fewer of them.
I think what a physician says is, "How is my patient doing?" First and foremost, if they're on therapy and they're doing poorly, then I think I want to try a new therapy, and we're starting to see that with Pombiliti + Opfolda. And then what we're seeing in Europe is for new patients, they're starting to preference Pombiliti + Opfolda. Again, we'll see how that plays out over time. And to be fair, naive patient population is a smaller portion. So the switch is a far more important dynamic to watch, but I don't really believe that physicians will say, "This is going to be the last-line therapy," or, "I'm going to save it for last," or, "I'm going to have to try one before I try the other." I believe that we'll be able to establish Pombiliti Opfolda as the preferred therapy over time.
As you get on formulary, are you finding insurance companies trying to do that?
Not at all. Actually, from an insurance perspective, yes, we're starting to see major payers put us on formulary, which makes sense. In the U.S., typically formularies are reviewed either every six months or every year, but in either case, that kind of puts us in the window right now for getting onto the formularies. We're seeing that. We haven't seen any pressure from payers other than on label, which of course is what we're prescribing for.
Got it. How, how are you communicating with the Pompe patients? They're a very active, vocal group. Genzyme, according to the doctors we spoke to, Genzyme mobilized them very effectively. One of them even used the word annoyingly to come in and ask for Nexviazyme. How are your communications and mobilization of the patient groups?
Yeah. So the U.S. is really the only market where you can educate patients directly, and there are rules around that, just like there are rules around educating physicians outside of Europe.
So not in Europe. You can't.
Yeah. Outside the U.S.
Is that changing at all?
No, that's pretty consistent. Now, there are still very active patient organizations, and so I think generally both the U.S. and in Europe, you're going to see word-of-mouth kinds of things, and I think that is a very powerful, very powerful motivator for patients. They're seeing people in their community. They're hearing about things online where, where they're talking about their experience with these different medications. And I think as more of them get experience with Pombiliti Opfolda, you'll see that happen. I think that will be important.
In the U.S., though, yes, there is a very directed patient education component to what we do that can be anywhere from patient meetings where a physician will hold a patient meeting and invite sometimes just us, sometimes both companies, sometimes companies that are developing things in, you know, that have things in development to come and speak on the product, so that's a direct opportunity. There are, you know, online kinds of education tools. We have a website and associated kind of awareness tools there. And then there also, again, I think there's patient advocacy organizations who have, you know, large meetings in and of themselves. I'm thinking like the AMDA is an example, which has a really important meeting in Texas where it's a big community of patients and physicians, and that's an opportunity.
That would be like a medical conference, effectively. So I think those are the three areas that we're primarily focused.
Got it. One of the conversations I've had since your earnings call is whether you gave de facto guidance on Pombiliti or not. So you said two things. You gave Galafold guidance, which sort of backed into $440-ish, $450-ish.
The midpoint, yeah.
Yeah, the midpoint of the range. And then you said $500 million plus, and everybody's like, "Oh, they're only going to sell $60 million of Pombiliti.
Right. Yeah.
Can you clarify that?
Yeah. So that was not intended. It's a very good question. We thought, first of all, $500 million is a really important threshold for sales, and we thought it was a nice round number, and it sounded, you know, good and exciting as a as kind of a waypoint to the future. I think the other important piece of that was that if you think about the conversation from an OpEx perspective, understanding that you're going to be well more than $500 million allows you to see how you're going to drive full-year profitability, right? And so to me, it was really more kind of a symbolic milestone as well as tying back to the profitability conversation. And it wasn't meant to be a back-ended or backhanded way of providing guidance. Otherwise, it would have been in the press release as guidance.
I, you know, look, I know people are, you know, really hungry to have some revenue guidance. It's clear that, you know, in the first year, it's just really hard. The timing of revenue in particular is just really hard to do. That's why we've really focused people on patient acquisition, patient trends. To me, it's the maximize the number of patients on the end of the year is what's going to tell you how this launch is going. Yes, the revenue is important, but in the context of Galafold and its growth, and, and where we are as an overall business, to me, it's much more the patient capture that will tell how the launch is going. Of course, once we get through this year, we'll provide revenue guidance as we did with, with Galafold as well in the second year.
Can you walk us through the sequences of Joe saying, "This is another thing that your competitor talks about with patients?" You mentioned at the conference this, like, "Oh, you have to wait and, you know, this and sequencing." So can you walk us through, like, a patient's morning? Yeah, like a patient's morning.
100%. So, remember, this is a two-component therapy, the small molecule, stabilizers taken orally, and then the patient take goes in for the infusion about an hour later. What I think is kind of interesting is that the biggest competitive pushback, maybe it's the most obvious, but maybe it's also the easier place to, you know, because they have a harder time on, on some of the other benefits, is to say, "Hey, this is more complicated. They've got to fast. It's this big, huge deal." So this is a typical patient morning. I think there's two versions of it. One is I wake up, I have breakfast. Two hours later, I take my pill. An hour later, I get my infusion, and an hour later, I can have coffee or.
Get in the car, find parking, go in, get the infusion.
Correct. Yes. Or, or they're in. That's one version: where you actually drive during that hour. The other version is where you're in the home and while they're reconstituting the ERT. And by the way, many of these patients take concomitant meds anyway, so oftentimes NSAIDs or antihistamines to manage the potential infusion reaction. So all the research we've done, we've talked to nurses about this. We've talked to patients about this. We've seen real-world evidence is that the reality is there's no real impact on the patient. It's very easy to take to put this into their regimen.
Once every other week. One morning.
It's one pill every other week. As I described, it seems to fit in very easily with the care.
So it's not every morning. It's just one morning.
No. Exactly.
Every two weeks.
A morning of their infusion.
That's your sequence.
Exactly right. Or you could see it the other way around. If they're getting infused in the afternoon, they have lunch. They wait two hours. They take the stabilizer. They wait an hour getting infused, and then an hour later, they can have their dose.
Infusion length is the same?
It's actually so the infusion length, because the unit volume in Pombiliti is much higher than the unit volume in Lumizyme, it's about half the amount of time to reconstitute. Similar infusion time, but the all-in process is actually shorter. Nexviazyme is similar unit volume, so they're roughly the same.
Let's run back to payers for a second. Now, we, we talked about the fact that the Opfolda part, you, you actually charge separate for Pombiliti and Opfolda, and there's different parts of the insurance. And again, KOLs were sort of complaining about it in the poster about, like, plans getting one part on formulary before the other. Can you talk to sort of whether payers are reasonably aligned on getting both parts covered at the same time such that it simplifies the doctors' lives?
Yes. And, you know, I think that's part of sort of that initial 90-day time from prescription to infusion that we talked about. But yeah, in what we have seen is that in general, payers are paying for both. The small molecule is a tiny fraction of the cost of the overall therapy. The frustrating thing, and this is just true, that because it's pharmacy benefit and medical benefit, the payers are oftentimes reviewing them separately. So it is two applications, two, two prior authorizations, if you will. But, but we're what we're seeing is we're getting through that process, and it's speeding up.
So the original clinical trial patients, and I know that's probably a lot of whom you were talking to at World, were more in that 90, you know, kind of day range, in part because of the payer process, but in part because they had to schedule the patients to come back into the hospital and do their end-of-study visit. So there's just more operational pieces to that. The newer commercial patients are going through the process faster than 90 days, and that will continue to speed up, we think, through the end of the year. The target steady state is probably about 30 days to go through that.
Got it. So now let's move to Galafold. Got it profitable. Happens to be making more than $400 million a year. So you put guidance, full-year 2024 guidance at 11%-16% year-over-year, constant exchange growth.
Correct.
Can you review for us the key drivers, key growth drivers that you expect to see unfold full year to get us there?
Yeah. So, there's really, I would say, three key drivers. We're now up to 60% to 65% of market share of treated amenable patients. Remember, amenable patients is about a third to a half of the overall population. So if you're sitting at, you know, $400 million, that means there's maybe another $200+ million in sort of switch opportunity out there, right, which is great. So we'll continue to switch patients. There is part of that story also is around geographic expansion. And so there are a handful of newly launched markets: Taiwan, Turkey, a handful of others in LATAM, where literally we're just launching now. And so it's kind of brand new markets. And Turkey in particular is a relatively sizable from a population perspective. It's, it's not huge from a revenue perspective, but numbers of patients are pretty, pretty large.
And then we have other markets: Brazil, a lot of the Latin American markets, some of the Southeast Asian markets where we are early in the launch still. So those, I would say, are still going to be majority switched companies. What was amazing, though, which we predicted, and I can talk about kind of the overall market and why it supports this, what's amazing, though, is you're also seeing this huge number of previously untreated, whether they're diagnosed but untreated or whether they're newly diagnosed patients come onto therapy as well. And what we said, the color we gave on the call was that, in fact, the U.S. and the EU5 had some of their best new patient starts since, like, 2019. So you're seeing huge growth in those markets, predominantly from naive patients.
If you take a big step back and think about how the markets evolved, I think it supports that sort of long-term, both near-term growth but long-term growth as well. When we launched, in the United States, there were 10,000 diagnosed patients, 5,000 treated, 5,000 untreated. It was about a $1 billion market. Today, there are 17,000 diagnosed patients, 11,000 treated, 6,000 diagnosed untreated. So too over $2 billion market. So and we think that dynamic's going to continue, which gives us a ton of room to grow this product over time.
In the last minute, let's talk about the fact that you have turned profitable.
Yes.
You've guided for full-year profitability. You're launching your two drugs. You still have two mothball gene therapy programs. How are you thinking about capital deployment as far as your pipeline? Because you have a Fabry and you have a Pompe, and there's nothing in active development for either of them. It's not like it's a crowded market. Yeah, challenging, but not crowded.
Agreed.
How are you thinking about it?
So, I not quite mothball, but very, very, very efficient investment, you know, less than $5 million last year went into those products. I would say what we're doing there is we're looking for opportunities to deliver our engineered transgenes through a more effective means than our original AAV vectors. That could be other gene therapy approaches, but could be other, you know, non-viral vector delivery approaches.
Technologies that you could bring in for that brand.
Technologies we bring. Exactly right. So what I would say is kind of 2025 and beyond, when we're fully profitable, generating our own cash flow, etc., think about starting to see a product or two go into the clinic, either through our own homegrown products or potentially through bringing something in from the outside that would be on strategy. So I think that'll be a growing part of the story over the next, call it, you know, two to three years.
Great. Well, Brad, we're at time. Thank you so much.
Thank you, Ritu.
This was very helpful.
Great. Thanks, guys. Appreciate it.