Amicus Therapeutics Inc

NASDAQ:FOLD

Earnings Call Analysis

Amicus Emphasizes New Therapy Launch Success

Amicus Therapeutics reported solid progress in launching their new therapies, Pombiliti and Opfolda, with global revenue guidance for 2023 set at around $10 million. They're actively engaging with doctors to ensure patient access and are already treating over 60 patients commercially. Total revenue for Q3 2023 hit $103.5 million, marking a 27% year-on-year increase, with the full year Galafold revenue growth guidance raised to 16-18%. Non-GAAP operating expenses are projected to be $330-350 million. The recent $430 million financial collaboration with Blackstone aims to align borrowing with revenue growth for long-term stability.

Growth Momentum into the New Year

Amicus Therapeutics, known for its concentrated efforts in treating rare diseases, has painted a picture of optimism in its Third Quarter 2023 Earnings Call. The company has highlighted its anticipation of sustained growth throughout the end of 2023 and into 2024, powered by factors such as market penetration, expanding geographical reach, and label extensions.

Strategic Expansion and IP Fortification

The company reported on the strategic moves to penetrate further into existing markets and to expand into new ones, like Taiwan, Lithuania, and New Zealand. Coupled with a robust intellectual property portfolio that extends IP coverage well into the late 2030s, Amicus ensures a fortified market position for its key product, Galafold.

Product Launches Driving Sector Standing

A transformative period for Amicus follows the approval and launch of Pombiliti and Opfolda in significant markets such as the EU, UK, and US, marking a milestone for the company by introducing multiple products into the market. The company communicated an effectively executed transition strategy for clinical trial patients to commercial supply, aiming to complete it by the year's end, indicating an efficient market assimilation.

Clinical Trials and Product Development

Continued investment in research is evident with ongoing trials like the open-label ZIP and Rosella studies, aimed at generating long-term data to substantiate the unique action and efficacy of their therapies. The reach of clinical experience is broad, with approximately 75 centers participating globally, reflecting a well-spread recognition in the medical community.

Favorable Financial Trajectory

The financial statements show positive performance with total revenue witnessing a 27% increase to $103.5 million, and significant cost management leading to reduced net loss. The company is on the pathway to non-GAAP profitability by Q4 2023, hinting at sailing towards financial stability amidst revenue growth.

Enhanced Revenue Forecast

Confidence in the demand for Galafold propelled an elevation in the full-year revenue growth guidance to 16%-18% at constant exchange rates. Their recent $430 million refinancing collaboration with Blackstone underlines a strategic financial restructuring to support long-term revenue growth.

European Market Expectations

Revenue influence from the European market is projected to boost in the latter half of the year, implying that current and near-term efforts will gear up to deliver revenue enhancements, with the second half being the focal point for realization of these gains.

Revenue Contribution from Newer Therapies

Revenue contributions from newer submissions across major markets outside the US, UK, and Europe, are expected to favorably impact the company's revenue profile by 2025, indicating groundwork for future success.

Commercial Progress and Payer Interaction

Amicus Therapeutics portrays a smooth ongoing process of approval and setup for therapy, with positive feedback from payers about their therapy transitioning. Notably, Lumazine and Nexvizine are contributing equally to their portfolio, showcasing diverse market penetration and acceptance.

Anticipated Shift in Patient Demand

The current year's revenue is heavily dependent on converting existing patients to new Amicus Therapeutics products. However, the upcoming year is expected to see the vast majority of demand coming from new commercial patients, signifying a pivotal shift in the company's commercial strategy.

Earnings Call Transcript 2023-Q3

[Operator]

Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics Third Quarter 2023 Financial Results Conference Call and Webcast. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Vice President of Investor Relations. You may begin.

[Andrew Faughnan, executive]

Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' Third Quarter 2023 Financial Results and Corporate Highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martel, Chief Business Officer; Simon Harford, Chief Financial Officer; and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Notal Officer; Ellen Rosenberg, Chief Legal Officer; and Mike Keavany, President of U.S. Commercial Business and Head of our Global Marketing. As represented on Slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved. Any or all of our forward-looking statements made on this call may turn out to be wrong you can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which fake only to the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and Risk Factors section of our annual report on Form 10-K for the year ended December 31, 2022, and the quarterly report on Form 10-Q for the quarter ended September 30, 2023, to be filed later today with the Securities and Exchange Commission. At this time, it's my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

[Bradley Campbell, executive]

Great. Thank you, Andrew, and welcome, everyone, to our third quarter 2023 conference call. I am very pleased to highlight the continued progress across our global business through what has been a tremendous third quarter for Amicus. As we did in this morning's press release, let me highlight several key points before I turn it over to the team to give more detail. First, Galafold continues its strong performance and remains the cornerstone of our success. We are very pleased with the commercial uptake of Galafold globally, which for the first time, has achieved over $100 million in quarterly revenue. Galafold's performance represents 19% growth from the third quarter last year on a constant currency basis. And on a year-to-date basis, Galafold revenue growth was 17%, both at constant exchange rates as well as in reported numbers. We continue to observe strong trends across our key performance indicators in all key geographies in the third quarter. This includes continued demand through new patient starts from both the switch and naive populations in all of our leading markets, a steady growth of in-person visits between our field team and Fabry treaters over the same period last year and sustained patient compliance and adherence rates of over 90%. Growth in the third quarter was driven primarily by patient demand from net new patient starts. Based on Galafold's strong performance throughout the first 9 months, we are increasing again our full year 2023 revenue growth guidance to 16% to 18% at constant exchange rates. Second, Pombiliti and Opfolda are novel therapy for late onset Pompe disease is now approved and launched in the 3 largest Pompe markets. Following the recent U.S. FDA approval of Pombiliti and Opfolda in September, the commercial launch is now well underway in Germany, the U.K. and the U.S., which again are the 3 largest Pompe markets globally. As Sebastian will cover in more detail in a moment, our team is making tremendous progress in converting individuals from clinical studies and expanded access programs to commercial supply in our reimbursed geographies. We're also already seeing new commercial patients who are switching from both of the available ERTs, and additionally, in Europe, patients naive to treatment coming on to commercial drug as well. We're pleased to share that as of early November, more than 60 patients are being treated with commercial product and multiple additional patients have been scheduled to start their treatments. We're very pleased to see the early days of the launch track ahead of our expectations. And importantly, we're well on track towards our goal of transitioning all clinical trial patients to commercial supply in these 3 major markets by year-end. Beyond that, we'll continue to focus on the broader patient access by expanding into the major European markets as we navigate the country-by-country reimbursement process and focus on additional regulatory submissions outside of Europe as well. By the end of this year, we will have submitted reimbursement dossiers in over a dozen countries. With the global launch of Pombiliti and Opfolda, we look forward to providing a real choice to challenging therapeutic expectations for both physicians and those living with Pompe disease. Finally, we've continued to maintain a strong financial position as we execute on the expansion of Galafold and advanced the global launch of Pombiliti and Opfolda. With the launch now well underway, the recent refinancing of our debt under more favorable terms and continued strong growth from Galafold, we are well on track to achieve non-GAAP profitability in the fourth quarter this year. Ahead on Slide 4, we're also making great progress towards achieving our key strategic priorities for 2023. First and foremost, continuing to sustain double-digit growth for Galafold around the world. On the back of our strong performance year-to-date, we have now raised the expected annual growth rate of Galafold to 16% to 18% at constant exchange rates. We've now secured regulatory approvals for Pombiliti and Opfolda by the FDA, EMA and NHRA and now are executing successful launches in those key markets. We've continued to judiciously invest in the advancement of our best-in-class next-generation Fabry and Pompe genetic medicines and capabilities as well as our next-generation chaperone for Fabry disease. And as always, we are maintaining a strong financial position as we carefully manage our expenses and investments and continue to grow the top line on our path to non-GAAP profitability. With that, let me now hand the call over to Sebastien Martel, our Chief Business Officer, to further highlight our commercial performance. Sebastian?

[Sebastien Martel, executive]

Thank you, Bradley, and good morning to everyone on the call. I'll start by providing you with more detail on our Galafold performance for the quarter. As you can see on Slide 6, for the third quarter 2023, Galafold reported revenue reached $100.7 million in revenue. Galafold growth continues to be driven by strong patient demand, particularly from our leading markets. Turning to Slide 7. Our results year-to-date highlights the strength of our global commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets, delivering operational growth of 17% over the same 9-month period in 2022 at constant exchange rates. From a year-over-year perspective, there's a negligible impact from foreign currencies. As a result, Galafold reported revenue growth versus the same period last year was also 17%. Galafold continues to be the fastest-growing treatment for Fabry disease globally, with 19% growth this quarter at constant exchange rates. In fact, both gross and net new patient starts have been higher this year than the previous 3 years. Our leading markets such as the U.S., the U.K., EU 5 countries and Japan remain the biggest drivers of patient demand. Throughout the first 9 months of 2023, a number of patients coming onto Galafold has continued to exceed internal expectations, which indicates continued growing demand for Galafold globally and help you return to a more normal post-COVID environment. We ended the third quarter with about 60% of the global market share of treated amenable patients. And within the global mix, we're seeing stronger uptake in naive populations. So we continue to achieve high market shares in a country where we've been approved the longest. And there's still plenty of opportunity for patients to continue to switch and to continue to grow the market as we penetrate into the Dinos and treat it and among people naive to treatment. All of that is underpinned by impressive compliance and adherence rates that continue to exceed 90%, reiterating our belief that those patients who go on Galafold predominantly stay on Galafold. As mentioned on past calls, due to a variety of factors, including uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically not near, and we expect that to continue into 2024. On Slide 8, we know there's a significant demand for Galafold and that segment of the global Fabry market made of patients with amenable mutations has the potential to reach $1 billion in annual revenue in around 5 years. We anticipate sustained growth throughout the end of 2023 and into 2024 to can be driven by several key growth drivers: first, continuing to penetrate existing markets, further uptake into the naive population on the dinosantreated population, expanding into new geographies and label extensions. As we just mentioned, all of these efforts are supported by solid compliance and adherence rates, positive reimbursement and access mechanisms around the world and increasing dinosis globally. I'm pleased to share that we continue to make progress on expanding Galafold into new markets and extending the labels. Just to name a few examples. We've recently received positive reimbursement for Galafold in Taiwan as first-line treatment for naive and eligible amenable patients. We've also received reimbursement in Lithuania on a named patient basis. Additionally, we've received approval in New Zealand and are engaged as we speak in pricing and reimbursement negotiations for Galafold in Hong Kong, Turkey and Singapore. In the longer term, we continue to see significant growth in the Fabry market globally, driven by diagnosing new patients through a variety of measures, including high-risk training, newborn screening and other diagnostic initiatives, which we continue to support. Also important to note here, we have often exclusivity in the U.S. and in Europe. And in addition to our now 54 Orange-Book-listed patents including 10 composition of matter patents that gives us IP coverage into the late 2030s. This provides us with the opportunity to provide access to Galafold globally for a long time to come. We intend to continue to protect and enforce our broad intellectual property rights. And looking ahead, we expect steady double-digit growth for Galafold through the end of this year and into 2024, and we remain confident that with our strong IP protection, Galafold as a long runway well into the next decade. Let's turn now to Pombiliti and Opfolda on Slide 10. We're incredibly excited to have Pombiliti and Opfold approved and launching in the EU, the U.K. and the U.S. Those 3 regulatory approvals are really a turning point for Amicus, placing us in the rare territory of biotech companies with multiple products in the market and on the verge of achieving non-GAAP profitability. On Slide 7, we outline our global launch progress with Pombiliti and Opfolda, which is being led by a world-class commercial and medical organizations. This launch leverages our highly experienced cross-functional teams to quickly transition all clinical trials and expanded access program patients to commercial supply and in parallel, ensure that treating physicians have the information they need to identify those patients who would benefit from starting on or switching to Pombiliti and Opfolda in each respective country. The process of switching clinical trial and expanded access patients in these first 3 geographies started right after approval and will be complete by year-end. The significant overlap of treatment centers, hospitals, physicians between Fabry and Pompe disease has allowed us to optimize our business infrastructure to support a seamless transition for patients. Within the first 30 days of approval, all core treating centers have been engaged with, and we've had very positive feedback from HCPs and other stakeholders as to our business approach, our support and our patient focus. As of early November, as Brad had said, more than 60 patients are being treated with commercial products and multiple additional patients are scheduled to start their treatment. Additionally, we've also started to see patients from both of the other approved therapies, switch over to Pombiliti and Opfolda. We expect Pombiliti and Opfolda revenue to come in around $10 million for the full year 2023, which is right in light with consensus expeditions. We're working in partnership with physicians to ensure that they have all the information they need on Pombiliti and Opfolda for their patients, and we believe our 2-component therapy is poised to have a significant commercial opportunity. Based on early interactions with Pompe experts, we're pleased with the positive feedback from physicians regarding patient experience and their engagement with the Amicus field team. Finally, within these early days, we find an important metric to track is our progress within access and reimbursement. We have a highly experienced team who are engaging in positive conversations with payers to demonstrate the value of Pombiliti and Opfolda. Today, as you know, we're launching Germany, in the U.K., in the U.S., and Austria. We're also active in pricing and reimbursement discussions with additional major European markets, as we focus on securing broad patient access throughout the EU. By the end of this year, we'll have submitted reimbursement in over a dozen countries. On Slide 12, I'm pleased to provide additional color on the even launch progress of Pombiliti and Opfolda by country. Maybe first, with Germany, I'm pleased to report that all expanded access in clinical translations have now been transitioned to commercial product. Additionally, individuals are now starting to switch from other therapies to Pombiliti and Opfolda in addition to lose naive treatment. We've also received very positive feedback from HCPs and pharmacies on their engagement with the Amicus team whose attentiveness has been critical in ensuring a straightforward transition process. In the U.K., we're seeing a very quick conversion of in-patients to commercial supply as well as switches from other therapies. As a matter of fact, these conversions are occurring ahead of schedule with now 100% of these patients converted as of yesterday. In addition, our field team has been quick to engage with all treating centers and HCPs in the U.K. to help facilitate a prompt conversion process. And in the U.S., all launch activities are underway, with first conversions progressing as planned. In fact, 66% of patients in clinical trials have already PRF submitted with their physicians, and they're on track, and we're on track to transition all clinical trial patients by year-end. Importantly, thanks to the launch readiness of our team, our multichannel programs launched within the first few days of approval and the field team has made positive headway with both prescribers and payers. So in summary, we're very pleased with the launches of Pombiliti and Opfolda across all the first wave of countries. The strength of our clinical data the in-depth experience of therapy effectiveness through EAP programs and the depth of talent we have at Amicus gives us great confidence in our ability to make a real difference to people living with Pompe disease. We believe Amicus is in a great position for a second successful launch. And with that, I will hand the call over to Jeff Castelli, our Chief Development Officer, to discuss the ongoing clinical studies and regulatory time lines. Jeff?

[Jeffrey Castelli, executive]

Thank you, Sebastien, and good morning, everyone. On Slide 13, we remind folks that we continue to build the body of clinical evidence for Pombiliti and Opfolda through our ongoing clinical studies as we execute on expanding commercial access through regulatory submissions. As we enter the second phase of launch, in addition to the various reimbursement doses that Sebastian just noted, we are in the process of submitting. We also have multiple ongoing or planned regulatory submissions for marketing approval in new geographies throughout 2024. Importantly, for the younger Pompe community, we continue to enroll the ongoing open-label ZIP study for children living with late onset Pompe disease and the ongoing open-label Gower's study for children living with infantile onset Pompe disease. And through ongoing clinical studies and the Amicus Pompe registry, we expect to continue generating evidence on the differentiated mechanism of action and the long-term impact of Pombiliti and Opfolda across endpoints and patient populations. Importantly, experience with Pombiliti and Opfolda is quite broad with approximately 75 centers, having participated in clinical trials in various access programs globally. Finally, as highlighted in the pipeline slide in the appendix for our earlier stage pipeline, we continue to focus on novel approaches for Fabry and Pompe, including gene therapy to deliver our engineered GLA and GAA transgene and the next-generation Fabry chaperone. With that, I would like to now turn the call over to Simon Harford, our Chief Financial Officer, to review our financial results, guidance and outlook. Simon?

[Simon Nicolas Harford, executive]

Thank you, Jeff. Our financial overview begins on Slide 15 with our income statement for the third quarter ending September 30, 2023. For the third quarter, we achieved total revenue of $103.5 million, which is a 27% increase over the same period in 2022. At constant exchange rates, revenue grew 22%. The global geographic breakdown of total revenue during the quarter consisted of $66 million or 63% of revenue generated outside of the United States and the remaining $38 million or 37% coming from within the U.S. Cost of goods sold as a percentage of net sales was 9.6% in the third quarter 2023 as compared to 16.4% for the prior year period. Total GAAP operating expenses increased to $111 million for the third quarter of this year as compared to $102 million in the third quarter of last year, an increase of 8%. On a non-GAAP basis, total operating expenses increased to $90 million for the third quarter of 2023 as compared to $85 million in the third quarter 2022, an increase of 5%. We define non-GAAP operating expense as research and development and SG&A expenses, excluding stock-based compensation expense, loss on impairment of assets, changes in fair value of contingent consideration and depreciation and amortization. Net loss for the third quarter 2023 reduced to $22 million or $0.07 per share as compared to a net loss of $33 million or $0.12 per share for the prior year period. Driven by the revenue growth of Galafold and capital expense management, we continue to make progress towards our path to non-GAAP profitability in the fourth quarter of this year. Cash, cash equivalents and marketable securities were $280 million at September 30, 2023 compared to $294 million at December 31, 2022. Turning now to Slide 16. I am pleased to share we have revised our revenue guidance for the year. We are increasing our full year Galafold revenue growth guidance of 16% to 18% at constant exchange rates, driven by strong patient demand. Our full year 2023 non-GAAP operating expense guidance remains at $330 million to $350 million. In October, we were pleased to announce the $430 million refinancing collaboration with Blackstone. Under the terms of the agreement, Blackstone will provide Amicus with $400 million in senior secured term loan to facilitate a refinancing that we have just done of our existing debt under more favorable terms, plus a $30 million investment in Amicus common stock. This strategic agreement allows us to better align our borrowing and anticipated cash flows as we continue to grow revenue for the long term. And with that, let me turn the call back over to Bradley for our closing comments.

[Bradley Campbell, executive]

Great. Thank you, Simon, Jeff, Sebastian, as well as a big thanks to all of our employees around the world who worked tirelessly for people living with rare diseases. Entering this next phase of the company, I am confident Amicus can continue to drive sustainable long-term value and deliver life-changing therapies to more people in need. And with that, operator, we can now open the call to questions.

[Operator]

Our first question, comes from the line of Tazeen Ahmad of Bank of America Securities.

[Tazeen Ahmad, analyst]

Maybe Brad, can you give us just a little bit more color on how you're thinking about the cadence of this launch? So you got approved at the tail end of the quarter. Should we expect any sort of seasonality as we continue to build out your relationships with the appropriate physicians? And at least near term, how should we think about the proportion of new patients that are going to be added versus those that you continue to convert from ERT?

[Bradley Campbell, executive]

And as we said, I think, overall, we're super pleased with where we are right now with the launch. I think you asked a few questions there, kind of cadence of new patients, distribution of conversion versus new patient starts and then is there any kind of seasonality. So I'll take the first one first. So cadence, what we've said is our goal this year is really to, first and foremost, convert the existing patients, both compassionate use and expanded access excuse me, and then also clinical trial patients. But as I think Sebastian highlighted on the call, we're making great progress there with significant, all the patients converted in Germany, the majority of patients converted in the U.K. and 2/3 of the patients having prescriptions and now working through that process in the United States. So I would say the majority of new patients this year will come from those conversions. But what we're really pleased with as well, and I think we talked about this, is we're already seeing patients switching from both existing ERTs in each of the markets. And in Europe, we're seeing new patient starts as well. So I think if you look at all those KPIs we're really pleased with how that's going. Once we get through that conversion process, which we're on track to do this year, then next year, obviously, the majority of patients are going to come from switching from existing therapies and then starting new patients as well in Europe and other markets. So really pleased with the progress so far. In terms of seasonality, I think just based on kind of the flow we've seen with Galafold, I wouldn't be surprised if we see a similar nonlinear kind of pattern as we go through the year, but we'll know a lot more as we progress through next year, and we can provide that color as we observe it so that you guys can, I think, model out the progression. I think clearly, next year will be a significant contribution of revenue from Pombiliti and Opfolda, in particular, as we maximize the run rate going into the next year.

[Operator]

Our next question comes from the line of Anupam Rama of JPMorgan.

[Anupam Rama, analyst]

In the slides, you noted related to Pombiliti and Opfolda that you're expecting to have multiple regulatory submissions in 2024 for the product. So what are the key regions that we should be thinking about here and when could they be contributing to the top line?

[Bradley Campbell, executive]

I think there's 2 things that are going on here. First is regulatory submissions. And then the other, of course, is the reimbursement process that's playing out in the rest of the major geographies in Europe. As I alluded to on the call, we'll have more than a dozen reimbursement dossier submitted by the end of the year. So I think you could start to see revenue from the European markets play out probably towards the back half of the year. We were really faster than average getting through the reimbursement process with Galafold. And I think you'll see, based on the value proposition and our pricing philosophy, I think you'll see similar fast pace. And I think as we go into next year, we can give a little bit more tight direction in terms of when we might see that additional revenue come on. Jeff, do you want to talk a little bit about the key regulatory submissions for next year and kind of how that should play out?

[Jeffrey Castelli, executive]

So we have ongoing submissions we're working on, others that we had planned in the other major markets outside of U.S., U.K., Europe for next year. I don't think we're going to list specifically which country, what dates yet at this point. But you can expect after those submissions next year in those Tier 2 markets that similarly to the other Tier 1 markets, we'll have reimbursement negotiations. So unlikely that those new submissions next year significantly contribute to revenue next year would more be a 2025 revenue boost from the second wave of submissions.

[Operator]

Our next question comes from the line of Ritu Baral of TD Cowen.

[Ritu Baral, analyst]

Brad, I wanted to ask about Slide 12 in the 66% patients received PRF. Can you clarify what the PRFs are? Are those start forms are they filled out start forms? I just haven't encountered that term before. And as you look at the profile of those maybe a handful of commercial patients that you have that aren't transferred and the start forms that you may be getting, how are you thinking of that split between the Myozome converters versus the Nexviazyme converters. And I think we're all really curious about what those Nexviazyme converters look like, like how long do doctors give before they're like, no, this doesn't work, we'll try something else.

[Mike Keavany, executive]

The PRF is a patient referral form, it's essentially our prescription. And the 66% is the percentage of those that have been sent into our hub from our clinical trial positions. So we have approximately 40 clinical trial patients and about 66% of those have already come in. So we're working on the reimbursement for those. We're doing all the benefits investigations figuring out what each payer's prior authorization form looks like and moving that with the physician to have the physician fill that out to move forward to commercial product. And reimbursement so far is going well. We have more than a handful of patients who have received full approval to begin therapy, and we're in the process of setting up that therapy now. As you know, different from Galafold, which was an oral this has to be set up every 2 weeks. So we have to plan out with the patient and with the provider when their last dose of the clinical trial product will be and when their first dose of commercial product will be. So that's going extremely well. We haven't really had any issues this far with payers in terms of moving forward with our clinical trial patients. And Brad, about half of our nonclinical trial patients have been Lumizyme, half have been next Myozyme. But Brad, if you want to move forward on that.

[Bradley Campbell, executive]

As Mike said, great distribution. And I think from a targeting perspective based on the label, any patient is ineligible switch patients. So we don't really differentiate between what we're talking to with physicians and patients around Pombiliti and Opfolda regardless of which therapy they're on in the United States. And so far, as Mike said, it's about half and half. And the kinds of things that we've talked about before were to is really focusing on that improvement language. So that just gives us such an important differentiating aspect to say, look, if your patient is not improving on their existing therapy, they should consider switching to Pombiliti and Opfolda, and we're already seeing great traction there. What we estimate, we have kind of 2 data sources in terms of how long we think a patient might need to be on Nexviazyme initially before they consider a switch from patients. They say they'd be interested in considering that as early as 6 months from physicians, they say they'd consider 6 to 12 months roughly in that time period. And if you think about the approval time lines, a significant number of patients who had switched from Myozyme are already in that 6 to 12-month window and you're seeing that play out. So all the metrics we're tracking look great so far and we're really eager now to begin the commercial switch process as well.

[Ritu Baral, analyst]

Well, Brad and Mike, are the number of PRF something that you would consider reporting going forward?

[Bradley Campbell, executive]

Yes. That's something we did with Galafold, Ritu, you might remember. And so I think that is a key leading metric in the U.S. where you go through that PRF process. So I do think we'll likely provide color on that in arrears, so looking backwards. We did it for an initial period, and then we focused more on patients. Once you get into kind of the rhythm, it's really patients on drug, but that's more important. So stay tuned for that.

[Operator]

Our next question comes from the line of Joseph Swartz of Leerink Partners.

[Joseph Schwartz, analyst]

Based on the figures you provided, it looks like you've already seen around 33 PRF since launch in the United States. I was wondering if you could give us any insight into how many of those are renewal versus expanded access patients? And are you still anticipating being able to convert all expanded access patients to commercial therapy by the end of the year? I think they were around 50 total. And how long do you think it might take to move patients from a PRF to commercial therapy? And then in the U.S., are you seeing any demand outside of the EAP that you can quantify for us? And how much lumpiness do you think there might be once you work through the initial EAP bolus, if you will?

[Mike Keavany, executive]

When we look back on Galafold PRF to shipment times at launch, it was about 60 to 90 days because it's a new product, payers need to go through their process, get it on formulary. So in general, it's about 60 to 90 days. We do, and we have here, we do get authorization sometimes more quickly than that. But on average, we're looking at the 60 to 90-day window for any really new rare disease product to get to the payer system. Over time with Galafold, we're a little over 5 years out now with Galafold. It's down below 30 days, and we would expect that trend to continue with Pombiliti and Opfolda over time. And so we don't really have a specific number yet on PRF to shipment time because we're just starting out. But we're anticipating the 60 to 90-day window with some coming before. We already have more than a handful of approvals from payers. And we just got some of those PRFs in the mid-October time frame. So we've already seen that go well in a couple of cases. But again, it will take payers a little bit of time to go through the product. The vast majority right now have been clinical trial. We've got a little bit more than a handful of patients who weren't in the clinical trial that we received PRF for. And as I said, some of those are switches from Lumizyme. Some of those are switches from next Nexviazyme.

[Bradley Campbell, executive]

So I think, Joe, as maybe I mentioned in answer to another question, the vast majority of patients this year will be conversion patients in each of the markets, but we're really thrilled that in the U.K. and in Germany and the U.S., we've already seen multiple new commercial prescriptions come in who are not conversions. And so I think this year, if you kind of project out to the end of the year, the majority will come from conversions, but our goal is to maximize the number of new commercial starts as well over the course of this year. And then keeping in mind the time frame that Mike suggested and looking at the stats in the other markets, our goal also is to convert all of the patients this year. And so next year, the vast majority of demand is going to come from new commercial patients.

[Operator]

Our next question comes from the line of Ellie Merle of UBS.

[Eliana Merle, analyst]

I guess can you give us a sense from speaking with physicians, any feedback that you're hearing either on the number or the percent of their patients that are declining or not improving on standard of care and also how physicians are deciding between your product and Nexviazyme in terms of switching a patient to a new therapy? And then earlier when you mentioned that 50-50 split between Myozyme and Nexviazyme, is that something that you think continues to play out longer term or how do you see that looking?

[Bradley Campbell, executive]

So over time, I think it depends on which market you're talking about. So in the United States, it's, I think, north of 50% of patients now have been reported to have come on to Nexviazyme. And so our anticipation is that you'll draw probably relatively equally from both of those segments because they're roughly equally weighted, maybe a handful more neckline patients. In other markets, you have a smaller penetration of Nexviazyme. So still the majority of patients are on Myozyme and I think there, you'll see relatively equally weighted distribution. And so I think it will be a market-by-market conversion rate. The most important thing is that the label and that we talked about this, and this is why it's so important, some of these key elements of label that is agnostic ensoreplacement therapy. So it doesn't matter whether the patient is on Myozyme or Nexviazyme, the physician and the patient are going to focus on the data. And we would remind people that we're the only product that has in a well-controlled study looked at patients switching from an active comparator to our product, and we've shown improvement in 6-minute walk and stability in forced vital capacity. So that's really the differentiated data set that we have that we are using to go talk with physicians around options for therapy.

[Mike Keavany, executive]

So we have done some market research and conversations with physicians and based on what they're telling us. It's 75% approximately of their patients are not improving, and that means they're either worsening or stable. And based on the data we have and the data that suggests there's a possibility for actually improvement in both age and switch patients. That really seems to be the main driver of a decision. A big one we've also seen, and remember, this is early days, majority of the current commercial switches are from our trial access patients. So it's a small end but it's really that potential for improvement in sort of the experience that either physicians or patients have had. And we think that those anecdotal reports of how patients are doing as that spreads throughout both the physician and patient community is going to be a big driver as well. But still early days, and we'll continue to listen to hear the specific reasons different patients are deciding to switch or physicians are deciding to have a patient switch. But we think it's going to be driven by efficacy and patient experience.

[Bradley Campbell, executive]

One place that you might look, Sarah, as we have talked about this before, there was an independent poster that was published at the World Congress that talked about individual, of course, case studies, but it was the center itself reporting on individual patient's response to therapy and how the switch process went. And I'll say that's a piece that is never going to show up in a data. It's not going to be something that a physician kind of promotes on, of course. But we've heard over and over again that the experienced team we have, both the sales reps themselves, the MSLs and medical affairs team in the United States, our patient hub, which helps people work through the reimbursement process. I think we've really established ourselves as trusted incredible partners, and that really makes a difference too. These are life-threatening diseases. These are big decisions for people to make. And I think Amicus has established ourselves as really trusted partners in this field. And I think that goes a long way towards physicians and patients wanting to take a different track and try and on building out probe.

[Operator]

Next question comes from the line of Kristen Kluska of Cantor Fitzgerald.

[Kristen Kluska, analyst]

You've obviously reported on a number of endpoints, but I'm curious in a real-world setting, what are the biggest drivers and what feedback they're looking to get from patients to determine whether or not their current therapies are suitable for them?

[Mike Keavany, executive]

So as Brad said, there's a number of different measures that physicians and patients use to assess how they're doing. Some of those do include when they come in every 6 months, they do get the sort of battery of more standard assessments. Many of those are similar to the trial assessments like the 6-minute walk or an FVC. But there definitely is variability across physicians on that measures they use. A big part of it is also just sort of their questions to the patient about how are you doing in your daily life on doing different tasks, walking them stairs are you having falls, etc. And then also, some of the physicians will look at Biomarks. So it's really that totality of assessments of how patients are doing. There could be opportunities within those 6 months more rigorous kind of assessments but also have check-ins with their physicians. But it's really sort of that combination of parameters that are looked at. And importantly, as we look at the U.S. and sort of the not improving aspect of the label, that is not specific to any endpoint or parameter. It's more sort of left to the judgment of the physician, the patient to sort of holistically assess if that patient is actually not improving or not.

[Operator]

Our next question comes from the line of Dae Gon Ha of Stifel.

[Dae Gon Ha, analyst]

One question on ATGA, Pombiliti and Opfolda. The remark you made about the naive patient experience in Europe. Pretty curious, what are you seeing there? What was the sort of cadence of events that led to that naive patient coming on therapy? And obviously, how do you see this kind of panning out going forward? Is this going to be a spread of the word and ballooning from there to go after the naive segment? And then second for Jeff, as you think about the next gen, obviously, the non-GAAP profitability is well intact. But how are you thinking about the next-gen molecules. We've seen some disappointments on the gene therapy front from Fabry and Pompe and obviously, next-gen chaperone, just curious how you're thinking about the patient segment you're going to go after.

[Bradley Campbell, executive]

So the naive segment in Europe, of course, it's early days, but we are pleased to already be seeing newly diagnosed patients or diagnosed untreated patients come on to therapy. That's a really important segment. Pompe is not quite as underdiagnosed as Fabry disease. But if you look at all the literature, as we've done newborn screening, as we've done high-risk population screening and other manufacturers are focused on those segments as well, you're still seeing a healthy diagnosis rate and so we continue to expect there to be newly diagnosed patients fueling the market for many years to come. And of course, just as we've done in Fabry, we'll invest in those as well. And I think, look, if you look at the literature, if you look at some of the work that Dr. Kishnani and others are starting to do, it is clear that, #1 patients are slipping through the cracks and are being diagnosed later in life well after they've exhibited symptoms that should warrant a treatment. But we're also looking much more closely at patients who maybe historically would have been seen as "stable" who are newly diagnosed. And if you look closely, this is a progressive genetic disease and I think there's a growing body of evidence and support from physicians to treat those patients earlier. So I think that will continue to happen throughout the Pompe community. As you said, Dae Gon, is a judicious investment at this point. We're focused on profitability and using a little bit of resources to keep those programs going, but the main focus is Galafold and Pombiliti and Opfolda, but do you want to talk a little bit about how we're thinking about the chaperone program, Jeff.

[Mike Keavany, executive]

And I'll start big on with the gene therapy programs briefly. So there, we have seen some challenges in the field for some of the gene therapy programs, continued challenges around durability and some of the safety and we know that manufacturing is a challenge in terms of costs and regulators are wanting to see, in some cases, that the gene therapy is bringing some aspect of superiority to justify some of the inherent risks of gene therapy. So I think you're going to see people focusing more on the patient segments that are not doing well in standard of care, whether you might be able to best show some aspects of benefit over approved therapies. Given that and our judicious investment in the pipeline, we think our transgene is the best-in-class, more potent than wind tape. But we're really looking at trying to solve some of the challenges around delivery and safety so that when we are able to more rapidly bring those forward, what we're bringing forward is something that really could deliver on that benefit over existing treatments. And in terms of the next gen chaperone, really there, it's still early days, but we're trying to see if we can expand sort of the number of amenable mutations as well as potentially improve upon Galafold in terms of efficacy. It's at a high bar. So challenging to improve upon the response in medical mutations, but we think that would be great down the line. In the future, when potentially Galafold Megogeneric have something that could be incrementally better, importantly, to expand amenable mutations. We know it's clear that there's a preference for oral administration of therapies where possible. So if we can expand that list of amenable patients, we think that would be a big impact.

[Operator]

Our next question comes from the line of Gil Blum of Needham & Company.

[Gil Blum, analyst]

Maybe looking more forward here to 2024. Currently, the majority of revenues are being recognized outside of the U.S., do you think this dynamic may change now that you've launched in Pompe?

[Bradley Campbell, executive]

Yes. In the Fabry markets, just based on the pricing dynamics, you've kind of historically seen a 70% to 30% distribution between ex-U.S. and U.S. as you saw in our reported numbers, that's drifting a little bit more towards 60-40 at this point for us. And I think with Pompe, you'll probably continue to see that slightly larger ratio of U.S. revenues versus ex-U.S. revenues. I think if you look at the existing Pompe market, it is more close to that kind of 60-40 split. So yes, I think that's a reasonable sort of long-term expectation as the balance of our revenue comes from both Pompe and Fabry. We'll, of course, continue to report on that distribution of revenue. And if there's changes in trends there, we'll guide people that way. But I think that's kind of a reasonable expectation for the next few years.

[Operator]

Our next question comes from the line of Jeff Hung of Morgan Stanley.

[Lee Hung, analyst]

For Pombiliti and Apollo, can you just talk about the impact you've seen from KOL and patient outreach in Europe? And how does that set your expectations for the pace and the impact of your research outreach efforts in the U.S.? Is there anything that you might see that be different in the geographies that you could highlight?

[Bradley Campbell, executive]

Probably the biggest difference between Europe and the United States is outside of the United States, there's no real opportunity to interact directly with patients, whereas in the U.S., you do have some medical education that can go towards the patient community. So there's a little bit more of a direct interaction there. We also have a team of patient education liaisons who are in the field who are helping with the infusion process. Many of these patients do home infusions. And so that's a slightly different dynamic as well. But by and large, you have a very active, very aware physician community and likewise, very active, very aware patient community. And so right now, the focus from Jeff and his team and from the commercial organization is on educating physicians, the availability, talking about the data, et cetera, and generating new evidence, which we'll continue to generate new publications and presence at medical congresses. But I think also you'll see a growing kind of word of mouth as more and more patients have experience with Pombiliti and Opfolda directly. I think you'll see that start to really play a part as well where either a family member or somebody through the community talks about their experience and encourages others to think about that experience as well. So I think that dynamic will continue to grow as more and more new patients have access to Pombiliti and Opfolda.

[Operator]

Our next question comes from the line of Salveen Richter of Goldman Sachs

[Salveen Richter, analyst]

Of the 75 treatment centers worldwide that have participated in the clinical trials and extend access programs, what percentage of the patient population is covered through these 35 treatment centers? And the second question is that you mentioned that patients are already switching from existing ERTs. We understand that the numbers are small, but is there any insight you can provide on how those patients are doing once they've switched over to Pombiliti and Opfolda?

[Sebastien Martel, executive]

So Pompe disease is treated with a fairly concentrated HCP group on a global basis. You've got differences on a country-by-country basis with some markets being very concentrated. The U.K., for example, has 6 main reference centers for those lysosomal storage disease. And you've got Germany at the other kind of the spectrum, which is a lot more fragmented. And so it really varies by country. In some you essentially deal with a very small number of key accounts in some way. And in others, you have to expand to a larger group, although like you would see typically for anywhere disease, we're not talking very broad number of physicians in the grand scheme of things, it's still somewhat concentrated.

[Bradley Campbell, executive]

So I think those 75 KOLs globally, they probably influence in some way, the vast majority of treatment decisions, so 75%, 80%, whether in the end, they actually end up being the treaters themselves. You've got home infusions. You've got as Sebastian articulated, both Germany and the United States, you have infusion clinics or more community-based physicians that are doing the infusions. So I think those top KOLs influence the vast majority of treatment thoughts and decision-making, which is important. In terms of the second one, how are patients doing, I think too early to know how the initial switch patients, it's first handful of weeks. We are getting very positive feedback, again, word of mouth from physicians and patients on the switch process and how they're feeling in the initial days. And so I think early signals are that it's very positive. I would, though, say in terms from a data perspective, you're starting to see us present on the long-term outcomes of patients from the PROPEL study and from our other boluses of patients. And I think that's where we're very confident in that long-term data being durable and consistent across patients.

[Operator]

That was your last question. This concludes today's conference call. Have a great day.