Here at the Bank of America Healthcare Conference, I'm Tazeen Ahmad. I'm one of the Senior MD Biotech Analysts here at the bank. It's my pleasure to have our next presenting company with us for the next 30 minutes. Speaking for Amicus Therapeutics is President and CEO Brad Campbell. Brad, thanks for making the trip out west.
First step is getting the mic to work.
You're on.
Okay, thank you. Thanks, Tazeen, and thanks to Bank of America for having us. It's always a pleasure to be here with you guys, and a great set of clients too, so I appreciate that. So maybe just a few words to kick us off?
Yeah, so maybe you could do the 2-minute intro about the company, and then we can go into specific questions.
Excellent, excellent. So as folks probably know, Amicus Therapeutics, we are a global biotechnology company. We focus on delivering next-generation therapies for people living with rare diseases. We have a core franchise with Galafold, which is our small molecule chaperone for people living with Fabry disease with certain genetic mutations. And that business has just continued to grow and grow, which is fantastic. We came into the year and reported our first quarter numbers with 16% growth, which was $99 million in revenue for the quarter. And importantly, that led us to raise our guidance for the year from 11%-16% to 13%-17% annual growth. So we're really excited to see that continue to go forward, and I know we'll talk more about the drivers of that growth and the opportunity there.
We think that product is on its way to $750 million-$1 billion in global sales. Our second product, which I know we'll also spend a lot of time on, our second therapy, I should say, is a two-component therapy, Pombiliti and Opfolda, for the treatment of late-onset Pompe disease patients. We do hope to bring in younger patients over time as well. That product was launched last year in the United States, in Germany, in the U.K., in Austria, and we just launched in Spain here recently, so really exciting momentum there. We gave guidance for Pompe of $62 million-$67 million in annual sales. We did that on our first quarter call, and I know we'll talk more about that. But really exciting to add that to the portfolio, to see that gain traction and build momentum.
We see that again as a $750 million-$1 billion peak product opportunity. Then I think the last piece for Amicus is now with 25%-30% top-line growth, with, I think, continued prudent expense management. We intend to deliver our first full year of non-GAAP profitability as we close out this year. I think lots of opportunity on the top line with both the core franchise, the new product, and now hopefully turning non-GAAP profitable for a full year and going forward.
Okay, perfect. Maybe we'll start with Pompe, and you can talk to us about the guidance that you gave.
Sure.
And yeah, so how are you getting to that $62 million-$67 million? What are the drivers that you look at? It's early in the year. How are you thinking about seasonality or geographic anomalies, for example, and getting to that number? I think people would be looking for color in that. I think Sell-side was probably a bit more bullish about what first-year sales would be. So interested in hearing how we should be thinking about it because maybe we've not been thinking about it correctly.
Yeah, thank you, Tazeen. Good question. So a couple of things that are sort of packed in there. So first and foremost for us, the goal has always been to maximize the number of patients on drug by the end of the year and to see, I think, healthy trends as relates to how we're getting those patients from the two competitor products, Lumizyme and Nexviazyme. And we'll talk a lot more about that. But that's the first piece, is maximizing the number of patients on drug. And we feel like we're in a great place now to be able to see how we're doing with that, and we're on a really good trend there. And in particular, what we shared in terms of new patient starts was we came into the year and reported 120 patients either on drug or scheduled to go on drug.
In the first quarter, what we said was the rate of new patient starts was nearly double of what it was last year. Then we shared that April was actually the best month we've had so far. That led us to report a number of 155 patients on drug or scheduled to start drug. Then we clarified, because it helps tie the revenue, that that was 135 patients on drug as of that time point. A couple of other trends that we look at, then I'll unpack the revenue piece and some of the geographic dynamics that you talked about. A couple of other important things that we look to see, the first is that we're taking share proportionally in the markets where we're launched.
So in the U.S., Nexviazyme, which is Sanofi's second-generation product, was launched a little over 2 years ago, so maybe 2.5 years. And so they have a 65% or 75% share of patients now on Nexviazyme. And that's exactly the rate of switches that we're seeing in the United States. So 75% of our prescriptions, our commercial prescriptions, I should say, came from Nexviazyme, and then the balance came from Lumizyme. Outside the United States, where Nexviazyme was launched much more recently, we're taking much more share from Lumizyme, which is the large portion of the population. But we're also getting naive patients, which is an important segment outside the U.S., and we're getting Nexviazyme switch patients too. So in terms of a switch dynamic, all of that is going really well.
Then the other piece, though, and I think this is probably the most unique dynamic for the U.S. in addition to the launch timing, also I think describes the disconnect from an expectations perspective and what we guided to from a revenue perspective. And that's really a timing of revenue perspective. In the U.S., as you know, you start with a prescription, and what we said is that we targeted about 90 days from prescription to infusion in the beginning of the launch. And then as you start to get on formularies in the U.S., both hospital and payers, we would like to see that trend down to more like 30-45 days. As of the Q1 call, we're down to 70 days, which is great. And what we shared is the more recent patients were more down to 30-45 days.
So all of that is going well. The one piece that was harder for us to anticipate, and I guess in hindsight makes sense, but I think this is part of the disconnect there, was getting the clinical trial sites to convert a clinical trial patient just to write the prescription took longer than we had anticipated. Why? Because they already have access to drugs, so there's not a lot of urgency. It was at the end of the year. It is a bit of a hassle to start that process for the first time. The new commercial patients have gone through much faster, and now we've worked through that clinical trial bolus. But I think that timing was a piece of what was the disconnect. Those are the higher-priced patients, so it sort of costs you more just from a revenue run rate.
The good news is we're through that process now. We're tracking towards that faster reimbursement timeline. Like I said, the more important piece, which is the patient capture and the switch trends, I think are showing us that this is on track to do exactly what we hoped it would do.
Okay, that's good color. You mentioned that 25% of your patients are ones that are switching from Lumizyme. Why would they skip over Nexviazyme?
I hope, and I believe it's because they think that Pombiliti and Opfolda offers them an opportunity to improve based on the data that we've demonstrated. Remember, we're the only drug that in a controlled setting had showed improvement when switching off of standard of care, in particular Lumizyme. So we believe it's because they see an opportunity for better outcomes on Pombiliti and Opfolda. I also think that historically there was only two options, Lumizyme and Nexviazyme, in the United States, and now you have PomOp available. And so I think physicians and patients are able to choose that for the first time.
Do you think that doctors are going to mostly follow the path of Lumizyme to Nexviazyme and then to the Amicus offering because patients over time stop responding to therapy or need something else? For the longest time, our doctor checks, for example, say, "We want to leave the Amicus product for last because we want to make sure that we can keep the patient on this for as long as we can." Just curious on what you're hearing on that.
Yeah, so we've heard that concept as well, which is eventually you're going to kind of step through Nexviazyme and then end up on Pombiliti and Opfolda. And sort of a flippant response might be, "Okay, that's fine. It means you'll get them eventually," right? So it's okay if we're considered the biggest gun to save for the end. The reality is I don't think that's how these products are working. And I think now that physicians and patients have a choice, the data we're seeing, which is now Europe and U.S., says that's not the case. I think the data says that physicians and patients are going to want to try to use the best product that they think is available to them. And I think we're starting to demonstrate that that's Pombiliti and Opfolda.
In Europe, as an example, the vast majority of the patients are coming from Lumizyme because those are the most patients that are available. The one market where we have sort of head-to-head-to-head data, which is the U.K., where we've been available together for about 2 years, both from the expanded access time frame and the commercial time frame, we've said this on the call, we're about one-third market share after 2-ish years. And again, I think there's every chance that over the course of this year we'll be the leading market share. And again, I think that's a preference choice.
Okay. So in Europe where you're not label-restricted to switch, why would a patient go on Pombiliti first, for example?
Yeah, I think it's for the same reasons, which is if you believe this is the best therapy, why would you start on an inferior therapy? And again, I know in other classes of medicines you have that kind of step-through concept. MS would be another good one, Parkinson's maybe. But I think in the Pompe world and a progressive genetic disease, I think you would want to start the best place you could. And in the European label, it very clearly acknowledges the outcomes we had in naive patients, a small portion of the population, but very clearly shows that there was an improvement in those patients who came on to Pombiliti and Opfolda.
Okay. So for the guidance that you've given for the year, is there a sense on what proportion of that is going to be U.S. sales versus ex-U.S.?
Yeah, just because, remember, we came into the year, we had 105 clinical trial and EAP patients from the three markets that we had launched. The majority of those, two-thirds-ish, came from the U.K. and Germany. And then, as I mentioned, even though the rate of new patient starts and the rate of prescriptions is quite high in the U.S. comparatively, it's the largest market of the three. In terms of that just revenue lag, it's still a smaller portion. So I think this year you'll see the larger portion of revenue, maybe two-thirds-ish plus, from Europe. Over time, the U.S. will become probably more like 40% of the revenue between all the regions. And that's largely because it's the largest single market, but it also has a significantly higher price point.
Yeah, on the price point, in general, what kind of discount should we expect to see in Europe over U.S.?
Yeah, so what we've shared publicly is in the United States, and remember our strategy is to maximize access, and we do that by pricing at parity or modest discount to standard of care, which is typically Lumizyme. So in the U.S., we priced at $650,000 list price, and that's for an average 70-kilogram adult. And then what we've shared is you can figure about a 20% net price off of that, so 80% is what you get, but a 20% discount, because of the mandatory Medicare and Medicaid 340B discount. So that's kind of the weighted average exposure to that buying segment. So that's what, a 520,000-ish kind of price point in the United States. Outside of the U.S., the average in Europe specifically, the average list price is about $400,000, and again, that's kind of pegged to Lumizyme.
Then you can assume behind the scenes that there are confidential discounts at a country level that get you to about, again, a 20% discount off of that list price. Call it $320,000 as an average price. Now, it may not be a surprise, but U.K., Southern Europe tend to be on the lower side of that corridor. Germany, the Nordics, Netherlands tend to be on the higher side of that corridor, but I think that's a pretty reasonable place to peg your average.
Okay. As you move forward, do you think you'll have any type of exposure to things like IRA, for example?
Not that we see, right? So number 1, we're orphan. Number 2, we're single-indication products. And when we've looked at the just sort of a risk mitigation, as we've looked at where we sit on the cost exposure for Medicare and Medicaid, it's hundreds of products down the list. So we're nowhere near on the radar screen today. I think there's very little risk for these products that be impacted by IRA.
Okay. Maybe let's just talk about manufacturing. Where is the product manufactured?
I'll give you one guess. So we're manufactured by WuXi Biologics. The current facility is in Wuxi, China. That's where the product was developed, and that's where we've had manufacture from clinical trials and launch. We took the decision with WuXi's capital to invest in another site. They built the plant. They invested in it, but we jointly agreed that we wanted to have a site outside of mainland China. And so that's in Ireland, Dundalk, Ireland. That product or that facility is well on track for the timeline that we had anticipated, which is getting to licensed product coming into the supply chain, call it back half of next year, early 2026. So that's been an important part of the evolution.
Then overall, and I'm sure we'll get into some of the congressional proposals that are out there, but overall, we have a supply chain risk mitigation strategy of having we target 18-24 months of inventory throughout the supply chain. Then we took the decision about a year ago to start to move a big chunk of that. We targeted about a year's worth out of China, so finished product out of China. And then since then, we've now evolved that so that we've pushed it even further into the U.S. and Europe and the U.K. So about 60%-65% of our product is outside of China today, which we think just gives us good sort of geographic and geopolitical mitigation on the current supply chain. But I know we could talk about kind of the next generation in the legislation.
Yeah, I did want to go into a little bit of detail on the Biosecure Act and what exactly that means because yes, you will be having a manufacturing site not located in China, but it's still owned by WuXi.
Correct.
As far as sourcing your API, would that still be coming from China, at least for the time being?
Yes. So we believe that WuXi, Ireland, would be included within the WuXi footprint if the Biosecure Act were to come to bear. And I'm sure folks follow it. But the proposal from the original version of the legislation effectively was looking to de-risk the United States biotech manufacturing away from China and also protect against Chinese companies from doing something nefarious with our human genetic data. So that was kind of the original impetus. What has evolved over time, which we knew it would, and now you could see in the latest markup of the legislation, is that what that original version didn't take into account, and I think what spooked everybody was it didn't acknowledge that you can't just stop manufacturing in China and start manufacturing somewhere else when you're talking about a biologic manufacturing process.
What you've seen in the latest draft of the legislation, which was the market coming out of the Senate, is now allowing for a grandfathering or a transition period. I've heard it sort of referred in different ways that would go out to 2032. So effectively says, if we pass the legislation, let's say, in the fall, then companies have eight years to transition away from China. I think that would also be intended to include component parts, API, etc. So from our perspective, that would give us plenty of time to transition the whole process out of China and put it into a different source or site of manufacture. The good news is we've already started that process. It wasn't with thinking about China or Biosecure.
It was frankly with an idea that, number one, we wanted to reduce the cost of goods of the product, and our target is by 20%-30%, which would be significant. Then number two, is it prudent then to have a second source, i.e., a second manufacturing partner aside from Wuxi? I think now that would prove to be a prudent decision. That would take us, we believe, about 4-5 years to execute from today. We think we have plenty of time to make sure we're in line with whatever legislation is passed.
Okay. I guess based on what you know about your API needs, do you know if the API can be sourced elsewhere?
100%. Yeah, we had already started that process too. Again, it's kind of just more supply chain risk mitigation. It wasn't specifically around this news, which the bill is only, what, two months old. But yes, the full stop, there are plenty of sources of all the component parts of Pombiliti that come outside of China.
Okay. What was it about Wuxi in particular that made Amicus all those years ago choose Wuxi as the partner? And what is it that you might need to particularly pay attention to if you're looking for a replacement?
I mean, look, full compliments to WuXi and to Chris, their CEO. They have built a hell of a business. I mean, they are one of the largest biotech manufacturing players out there. Their top-line revenue has grown like gangbusters. And I think for us, it was we were their biggest client for a long time. Now, I think we're still their sort of top three clients. It was really just a really strong partner willing to do really good technical work and manufacture at the highest quality standards and invest a ton of capital in building out their capacity, not just at WuXi, but then in Ireland. So yes, we pay overhead margins to them, but that was all their capital. And so I think for all those reasons, they were a great partner.
And by the way, a year ago, we were talking about inspection risk and what happened with the inspection and all that other stuff. Super clean outcome on the inspection. I mean, they've done a great job from a quality perspective. So they were great partners. If the geopolitical world puts us in a position where we can't work with them the same way, so be it. But what we would look for in a new partner, the good news is we already have a handful of potential partners we've identified who both have the capabilities, technical capabilities with perfusion, biologics manufacturing, but also have existing facilities that have the capacity to be able to do this. So I think we have great line of sight into a handful of partners.
It's not everybody, for sure, but we have a handful of partners who obviously would be domiciled outside of China that would be able to do this.
Okay. That's good to know. Would that take in terms of your OpEx, how would that impact investments that you would need to make?
Yeah, the good news is we had already assumed, like I said, we were going to develop this new process and then transfer it into a new facility, for sure. And so that's kind of baked into the numbers that we've talked about historically, which is we see R&D OpEx as relatively flat, modestly increasing with merit increases over time and a small amount of going to this, but it is baked into our sort of go-forward bullishness on top-line revenue growth and increasing profitability. So investors should not assume to see additional expense put towards this as a new project. It was already baked in.
Okay. Now, going back to the launch metrics for a couple more minutes, you talked about over time, you expect U.S. to be about 40% of the contribution that you get from Pompe sales. Does that assume that it stays as a switch market only in the U.S.? And what potentially could be an advantage of trying to also have a treatment-naïve segment?
Yeah. So yes, right now, our assumption is that we don't have a label for naive patients in the U.S. And so I still fully believe that that $0.75 billion-$1 billion is achievable without a naive label. What we said coming into this year and probably the next year or 2 is let's see how important that segment is outside the United States. We're already collecting registry data, which would include naive patients from countries outside the U.S. There is precedent now with the Fabrazyme full approval for using registry data to expand label in the lysosomal storage disease space. So one option very well could be let's get 3, 4 years of registry data and then use that to apply for an expanded label. A more costly version of that could be let's do a new naive study kind of head-to-head.
I just don't think that we're going to need to do that. That option is still open to us, but I think it's much more likely that either you have a fast enough uptick with the switch market alone because that is by far the largest pool of patients, or as I said, you get enough registry data and say, "Hey, you know what? Let's take a try with this and expand the label, again, 3-5 years from now.
Okay. Then you also talked about the time from writing the script to the patient get any infusion. The early assumption was 90 days, then it went to 70, and it's now, what, 30-45-ish?
I wouldn't call that a trend yet, but we did have the two most recent patients went through in that kind of timeframe. I think by the end of the year, we'd like to be down to that level, and we're on that journey.
Okay. So that would be your ideal.
A steady state.
Yeah, ideal state of time to turn around. I guess for doctors who have not yet written the script, what's the main reason, do you think?
Oh, look, I mean, so what we've been focusing on in the U.S., everywhere really, but in the U.S., is both broadening, meaning getting docs to write repeat prescriptions, and sorry, deepening, which is repeat prescriptions, and then broadening, which is more sites. And what we've seen, and I think Sébastien provided a little bit of color on this, is we are seeing exactly that. So in the first quarter, we saw multiple new prescriptions from multiple new sites, not just tier one sites, but also some tier two sites as well, which sort of gets to that breadth. In terms of why hasn't somebody written a prescription yet, I think part of it is do they have a patient in the sort of patient journey that they would expect? And then number two, obviously, is are they convinced that Pombiliti is the best therapy for them?
I would say where we're getting the obvious early traction is in the declining patients. I think that's natural. We talked about kind of the differences between a Nexviazyme decliner and a Myozyme or Lumizyme decliner. Then kind of the competitive fight, which is right where we are right now, which we described as kind of the stable middle, which is physicians probably estimate 50% of their patients are stable, 25 maybe improving, 25 declining. I think that's where we take this product from $750 million- $1 billion. Once we convince patients and physicians that they have a chance for improvement, which is what our label says and what our marketing materials say, then there's going to be more urgency for them to say, "It's not good enough to be stable." What I really think we can aspire to is improvement.
That's going to be, I think, the competitive fight for the next handful of years.
Just remind us how big of a marketing organization you've created for this particular launch.
So there are about 150 field-facing people globally. We added a handful to support the Pompe launch. The sales force and the field medics, the medical affairs people or MSLs in the United States, have largely stayed the same. We did add some direct marketing people, some direct medical affairs people in the United States. We added 4 patient education liaisons, which are field-facing patient educators. Then we added to our Amicus Assist Hub, which is the people that help go through the prescription process. So we feel like we've invested what we need to to support the launch. Could you add 1 or 2 people over time in different markets, maybe, but the vast majority of the investment's been made already.
Okay. So assuming that your sales force is now detailing both Fabry and Pompe, is there any concern that the momentum for Fabry could be impacted as sales reps need to start building out those other relationships?
I mean, that's always a concern. I feel like it's something the board always would ask you, and you'd always have to. We would ask our senior leadership on the commercial side. And I would offer a few things. First of all, we have super experienced salespeople and medical people and sales leadership who've done this before, who've launched multiple products in the rare disease space. We also did a study that said how much of your business overlaps, and what we found was about a third of treaters actually overlap, prescribers are the same, about 50% of the academic centers are the same, and 80% of the cities are the same. And remember, these are really conversations. They're not dropping off samples or saying hi to the intro nurses or whatever. These are really medical conversations with the physicians.
So we very much felt like the team we had was sufficient enough to be able to support those conversations. In terms of a distraction perspective, I would point to Q1 and fourth quarter last year as the proof that we can do both, right? That we can continue to grow Galafold, but also successfully launch Pombiliti.
Okay. So I don't want to leave Galafold out of the conversation altogether. So as you think about this is a mature launch for Amicus now. Maybe it's more mature in Europe because you launched there first. How are you thinking about what is left for you in terms of market opportunity? Let's talk about Europe and then also the US.
Sure. Yeah, it's a great question. We've continued to be just really pleased with the growth. We've always been bullish about Galafold, but we raised expectations this year. We did it last year. So we just continue to see just that robust growth. And where is it coming from? Part of it is we're still switching some patients. We have a little over 60% global market share of treated patients. In the big markets, Europe and in the US that we've been launched the longest, it's probably like 15% or 20% of new patients are switch. So there's still some laggards. There's still some that might have started on the competitor product first, and then we're switching them. But it's the minority, but it's still out there. But on a global basis, another 40% market share is pretty big.
We know we can get to 90%-95% in our most mature markets. That's our aspiration. You have this big pool of diagnosed untreated patients as well as newly diagnosed patients. That's the lion's share of the growth, even in the U.S. and in Europe. Diagnosis, if anything, is only picking up. I think we shared the stats, like 10,000 patients diagnosed when we launched, 17,000 patients today, 6,000 diagnosed untreated. That dynamic has really continued to support the growth of the product.
For the ones that are diagnosed but not treated, what's the reason?
I think it's largely kind of where they are in their disease progression, right? So this is a progressive disease, but because of better screening techniques, cheaper genetic testing and newborn screening where you find family members, you're finding people in their 30s, 40s, 50s who, yes, they probably have signs and symptoms of Fabry, but maybe they don't feel like they have the disease burden. But for sure, those are going to progress eventually to needing treatment. And I think an oral therapeutic like Galafold with our safety and efficacy profile is a perfect place for patients like that to start. And that's what we're seeing. Actually, if you look overall from launch, we're now at like 58% of all of our patients came from either newly diagnosed or diagnosed untreated patients, and 42% were switched. So we've actually grown the market significantly.
Yeah. Have you had to use any discounting to get on formulary or stay on formulary since you launched?
No, it's been one of the great things about this space, and that maybe goes back to your IRA point in terms of just the durability of the pricing and commercial opportunity here. We've done a really good job keeping pricing relatively flat outside the United States, which is great, even though they kind of go through annual review processes. And then in the U.S., we've stuck to our pricing promise, which is only raise price annually with CPI. And we've stayed there, and we've continued to be able to get those prices.
Okay. We're almost at the end, but I did want to ask you about how you're thinking about BizDev because you're now a company that's just purely focused on two commercial launches. In the past, Amicus did have a pipeline. You made some changes to the company. How are you thinking about where the company is now and whether or not you think investing in a pipeline again might make sense?
Yeah, thank you for that question. I think the long-term vision for Amicus is we have to continue to grow those products. We'll do that. I think they've got a great trajectory for many, many years to come. That will drop a lot more profitability to the bottom line, which would allow us eventually to be able to invest in a pipeline. I think in the near when we can do it on our own resources, I think in the nearer term, 6, 12, 18 months, kind of in that timeframe, I think there is an opportunity to find later stage or commercial assets where we can leverage our ex-US infrastructure, where we can actually amplify that financial trajectory on. And so that, to me, would be a first step.
And then maybe think of kind of a horizon in their early days in terms of their sort of stepwise approach. And then eventually, three to five years, I'd like to see us be able to afford a pipeline that sort of extends the runway as well.
Okay. Perfect.
Great.
With that, we're out of time. So thanks, everybody, for joining us. Thank you, Brad, for flying out to see us, and hope everybody has a great rest of the session.
Anytime. Thank you.