Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics second quarter 2022 financial results conference call and webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. Should anyone require assistance during the conference, please press star then zero on your touch-tone telephone. As a reminder, this call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Executive Director of Investor Relations. Please go ahead.
Thank you, Cole. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' second quarter 2022 financial results and corporate highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer, Daphne Quimi, Chief Financial Officer, Sébastien Martel, Chief Business Officer, and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman. As referenced on slide two, 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 the forward-looking statements made on this call may turn out to be wrong and 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 speak 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 and on our quarterly report Form 10-Q for the quarter ended June 30, 2022 to be filed later today with the Securities and Exchange Commission. At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Brad?
Great. Thank you, Andrew, and welcome everyone to our second quarter 2022 results conference call. Before we dive into the results of the quarter, I'd just like to start with a deep thank you to John Crowley. As planned, after 17 great years leading Amicus as our founding CEO, John has officially assumed the role of Executive Chairman of Amicus for a two-year term, after which he is expected to continue as the non-executive Chairman of the board. It has been an honor working alongside him for 16 of those years, and it's been through his leadership and unwavering commitment to all of those living with rare diseases that Amicus is in such a great position today. I'm honored now to assume the role of President and CEO and very excited about the opportunities that lie ahead.
Amicus has strong business fundamentals and a positive momentum to build on. We are poised now for the next chapter of our growth as we seek to get our second medicine approved and launched around the world. I firmly believe that we have the right people and the right assets to deliver on our mission to continue to bring great medicines to people living with rare diseases and create great value for our shareholders. Building on our commitment to patients, leadership in rare diseases and global operating platform, I am confident that we can achieve those two objectives. With that, let me get started on today's updates. I'm pleased to highlight the successful first half of the year across our business. As we did in this morning's press release, let me highlight several key accomplishments. First, Galafold continues its strong performance and remains the cornerstone of our success.
We continue to be very pleased with the uptake of Galafold globally, despite the significant foreign currency headwinds that's faced our industry this year. The first half of the year represented 11% reported revenue growth or 18% on an operational revenue growth basis. In the second quarter, operationally, our growth and key performance indicators are meeting or exceeding our objectives in all key geographies, and we are reiterating our guidance at constant exchange rates. Sébastien Martel, our Chief Business Officer, will provide further detail later in the call. We are also excited to announce that the Galafold intellectual property estate continues to grow this quarter. This year alone, we have strengthened our IP estate through the issuance of 17 new patents.
There are now 44 Orange Book listed issued patents related to Galafold in the United States, 28 of which provide protection to 2038 and beyond, and importantly include three newly issued composition of matter patents, bringing the total now to four. We see this patent portfolio, along with our orphan drug exclusivities, providing broad and long-term intellectual property rights well into the late 2030s for this novel precision medicine. Importantly, we believe we are well-positioned to address any potential generic challenges to our patents. Looking ahead, we expect continued growth for Galafold this year and with this strengthened IP protection, continue to believe it has a long runway well into the next decade. Second, we continue to make progress on our global regulatory filings for AT-GAA, our novel next-generation therapy for Pompe disease.
The U.S. and E.U. regulatory reviews are progressing very well, and we're very pleased with the level of engagement from both regulatory agencies. Clearly, all eyes are on the FDA inspection at the WuXi Biologics facility for ATB200, the biologic component of AT-GAA. We remain in active dialogue with the agency on how best to support an inspection, and we, along with our colleagues at WuXi, are fully ready to welcome FDA inspectors to the WuXi facility in China. However, as of today, they have not yet conducted their inspection. If the FDA inspection does not take place in the appropriate time, it goes without saying that it could impact the timing of approval. That being said, the good news is we are in late-stage label discussions and are highly confident in AT-GAA's potential approval in the United States.
At this time, we continue to expect that the two components of AT-GAA will be approved together by the October 29th action date. Importantly, in Europe, we're now actively engaged with the EMA on the marketing authorization applications for AT-GAA. We continue to expect a positive CHMP opinion later this year and commercial launch in early 2023. As a reminder, the EMA has indicated it does not require an inspection of the WuXi manufacturing site as a condition of their approval. I'm also extremely pleased today with the level of interest we are seeing in our expanded access programs globally. Today, we announced the first reimbursed access to AT-GAA has been granted in France under their Compassionate Access Program, which was formerly known as the Nominated ATU program.
Additional access programs are in place in the United States, United Kingdom, Germany, and Japan, with a growing number of patients participating in each. Across all of our ongoing clinical studies and access programs, there are now more than 175 patients on AT-GAA today, which we believe represents 5% or more of the total treated Pompe patients around the world. Our global launch plans continue to move ahead, including pre-launch activities, target investments and additional personnel to support the launch, significant investments in the launch and inventory preparations. We are now closer to having another potential treatment option for Pompe, for patients living with Pompe disease, both in the United States and Europe, with further regulatory applications planned in the months ahead.
Third, importantly, Amicus has maintained a strong financial position and remains committed to achieving profitability in 2023 as we continue to execute on the global expansion of Galafold and prepare for the global launch of AT-GAA. We are rapidly approaching two pivotal inflection points for Amicus. First, the global launch of a second rare disease medicine with AT-GAA, and second, achieving profitability. These are rare feats that we believe will enable Amicus to truly enter the upper echelon of rare disease-focused biotechnology companies. I'll emphasize that we are sharply focused on three key objectives, continuing to advance Galafold to as many patients in as many geographies as possible, securing approvals for and launching AT-GAA globally, and ensuring the financial strength of Amicus.
On slide five, we see we're well on our way now towards achieving our key strategic priorities for this year, including continuing to drive Galafold to more people living with Fabry with amendable variants in existing and in new markets. We look to achieve double-digit global product revenue growth of 15%-20%, with revenue of $350 million-$365 million at constant exchange rates. This reflects the strong momentum and demand behind this precision medicine globally. We remain steadfast in our commitment to advancing AT-GAA regulatory filings and initiating the anticipated launch of AT-GAA in the United States. Leveraging our seasoned global commercial team and experience across all areas needed for an effective drug launch, we are fully prepared and anticipate a very successful launch for AT-GAA. We are strategically advancing our best-in-class next-generation genetic medicines and capabilities.
Again, we will continue to maintain a strong financial position as we carefully manage our expenses and investments going forward. With that overview, let me now hand the call over to Sébastien Martel, our Chief Business Officer, who can further highlight the Galafold performance. Sébastien?
Thank you, Bradley, and good morning to everyone on the call. I'll start by providing you with more details on our Galafold performance for the quarter. On slide seven, as you can see, for the second quarter of 2022, total product revenue reached $80.7 million, driven by strong patient accruals, partly offset by foreign currency impacts, as well as the timing of orders in certain ex-U.S. markets. The geographic breakdown of our revenue during the quarter consisted of $53 million, or 66% of revenue generated outside of the U.S., and the remaining $28 million, or 34%, coming from within the U.S. This is roughly in line with a 70/30 split that we expect as we continue to grow both parts of the business.
Turning to slide eight, our results in the first half of the year highlight the strengths of our global commercial efforts. The business continues to be incredibly resilient, with patients added in all major markets and an operational growth rate of 17.8% over the first half of 2021 at constant exchange rates. The negative impact from foreign currencies was 6.9% in the first half of the year, and as a result, Galafold reported revenue growth was 10.9% in the first half of 2022. Just to add a bit of color on our geographical performance. In the first half of the year, our sales in the U.S. grew 16.1% at CER, while our ex-U.S. sales grew 18.5% at CER.
Galafold continues to be the fastest-growing product for Fabry disease globally and has been the greatest contributor to global Fabry market growth over the last 12 months. I'm pleased to report our monthly net patient trends continue to show positive signals. For example, the three-month trend is higher than the six-month, which is itself higher than the 12-month. In the U.S. in June, we also delivered the highest number of net new patients and PRFs since April of 2021. If you look at the growth in net patients on Galafold on a global basis, which is perhaps the truest measure of our underlying business performance, we see greater than 19% growth in patients on Galafold at the end of Q2 this year versus the same period last year. All indications of the continued demand for Galafold.
We ended the second quarter with a little under half of the global market share for treated amenable patients. While the global mix remains about 55% switch and 45% naive, in many, many geographies, we're starting to see stronger uptake in naive populations. While we're achieving high market shares in countries where we've been approved the longest, there's still plenty of opportunity to continue to switch patients over to Galafold and to continue to grow the market as we penetrate into the diagnosed and treated segment and the newly diagnosed segment. 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 generally stay on Galafold. We did experience some impact due to the timing of orders in the second quarter, and we expect this nonlinear quarterly growth to continue.
This order pattern led to a handful of orders being recognized in the beginning of the third quarter. Importantly, the value of Galafold continues to be recognized by payers as we have a very strong track record of successfully negotiating and renegotiating reimbursement outside of the U.S. Our relentless focus remains on ensuring access to Galafold for anyone who needs it. Next, on slide nine. What we've seen so far this year is that Galafold uptake continues to track very well, and we're seeing growth across all our major markets as well as most of our smaller markets. We're on track to achieve full year revenue guidance of 15%-20% growth at constant exchange rates, and our first half growth of 17.8% at CER is right in the middle of that range. Altogether, we view this as a great first half of the year.
Moving to slide 10. We know that Galafold has the potential to surpass $500 million in annual revenue over the next few years through three key growth drivers. First, continuing to penetrate into existing markets. Second, expanding into new geographies. Third, broadening the labels. I'm pleased to share that we're making continued progress on expanding into new markets. Just to name a few examples, we expect marketing authorization in Turkey this year. We have filed in the second quarter in Hong Kong, and in Chile, we're in pricing and reimbursement discussions. In the longer term, we continue to see significant growth in the overall Fabry market globally. This will be driven by diagnosing patients through a variety of measures, including high-risk screening, newborn screening, and other diagnostics initiatives which we continue to support and invest in as well.
Finally, we have orphan exclusivity in the U.S. and Europe in addition to our now 44 Orange Book-listed patents that gives us IP coverage into the late 2030s, 28 of which provide protection through 2038, and that includes three new composition of matter patents. This gives us opportunity to provide access to Galafold globally for a long time to come. On slide 11, let's shift gears and I'll provide you here with an update on our launch preparations for AT-GAA, as we're poised for another successful product launch. Unlike when we launched Galafold, and at the time we were hiring and building the commercial infrastructure from scratch, we now have a presence in over 40 countries around the world, including all the major markets.
That team will be largely the same that will launch AT-GAA with only a handful of new FTEs needed. For example, key account managers, MSLs. We have experience across all areas that are needed for a successful drug launch, from regulatory to commercial, supply chain, experience with payers, reimbursement and access, in addition, maybe most importantly, the key relationships with physicians. We're confident in our world-class commercial organization. We will leverage their experience and relationships and deliver AT-GAA to people living with Pompe disease around the world.
From the team, the medical education, the published phase III data in the highly regarded The Lancet Neurology journal, our experience with reimbursement and access around the world, and again, all the strategic planning that we're doing together with our partners at WuXi Biologics, we believe we're in a very strong position for a second successful launch of AT-GAA. With that, let me now hand the call over to Dr. Jeff Castelli, our Chief Development Officer, to highlight our AT-GAA program pipeline update. Jeff?
Thank you, Sébastien, and good morning, everyone. Moving on to slide 13, we'll start with our AT-GAA program. We recognize that Pompe disease poses a range of health challenges for people affected by the disease, and having therapeutic options is crucial. Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders. We've now seen multiple publications and natural history studies that highlight the initial benefit of treatment often being followed by continued long-term decline on key measures of disease for many individuals. Slide 14 presents a summary of the primary and key secondary endpoints from our phase III study. As a reminder, PROPEL is a randomized study addressing and assessing the efficacy and safety of AT-GAA in adult treatment naive and ERT-experienced participants with late onset Pompe disease, or LOPD, against the approved therapy, alglucosidase alfa.
PROPEL is the only controlled clinical trial to date that included this ERT-experienced patient set which represents one of the greatest groups of patients with unmet needs. Endpoints across motor function, muscle strength, pulmonary function, patient-reported outcomes, and key biomarkers, including the two most recognized endpoints in Pompe, six-minute walk distance and forced vital capacity, shown here on the slide, favored AT-GAA over alglucosidase alfa in the overall population. We believe this consistency of effect across the key disease manifestations illustrates the potential impact of AT-GAA for patients living with Pompe.
Additionally, in the ERT-experienced population, where 95 participants were on the standard of care for more than 7.5 years on average, which is generally associated with the decline phase of disease for most patients, we actually saw an increase in six-minute walk distance and stabilization in FVC, which both achieve nominal statistical superiority versus the current treatment and showed a clinically meaningful outcome never before seen in this population. Moving on to slide 15, adding to the overall body of data behind AT-GAA, at the 2022 MDA Clinical & Scientific Conference earlier this year, the Amicus team presented positive long-term data from the phase I/II study of AT-GAA. As seen here on the slide, these latest data continue to represent very meaningful and durable improvements in functional outcomes, as well as persistent reductions in key biomarkers of muscle damage and disease substrate out to three years.
These results have been shared with the regulatory authorities in the U.S. and E.U. as part of their ongoing reviews. Comparing these results with what is known about the natural history of both untreated and ERT-experienced Pompe patients, these durable results give great hope that AT-GAA indeed has the potential to become the new global standard of care for people living with Pompe disease. On slide 16, we've highlighted key updates on the AT-GAA program. First, on the regulatory progress. Last year, the U.S. FDA accepted for review the BLA for cipaglucosidase alfa and the NDA for miglustat, the two components of AT-GAA. In May, the agency extended the PDUFA action dates to August 29th for the NDA and October 29th, 2022 for the BLA.
As Bradley mentioned, we expect these filings will be approved together by the October 29th action date, dependent again on the ability for FDA to conduct an inspection at the WuXi manufacturing facility. We've also shared that the MAA has been submitted to the European Medicines Agency and is under review. The CHMP opinion is expected later this year. Of note, the EMA has indicated in writing that based on the extensive and prior manufacturing inspections of the WuXi facility, an inspection is not required for AT-GAA approval within Europe. We now have multiple expanded access programs in place, including in the U.S., U.K., Germany, France, Japan, and others. This includes the EAMS framework that we announced in which AT-GAA was granted a positive scientific opinion through the Early Access to Medicine scheme by the U.K.'s MHRA.
This positive opinion recognizes the high unmet medical needs faced by the Pompe community and permits eligible adults living with LOPD who have received alglucosidase alfa for at least two years to switch to AT-GAA, granting access prior to marketing authorization in the U.K. As Bradley mentioned, we're seeing significant enthusiasm for AT-GAA under the EAMS mechanism, with multiple physicians now having requested access across all the leading Pompe centers in the U.K. and dozens of patients now receiving this novel two-component treatment. Since the positive scientific opinion, interest, and momentum for AT-GAA has grown, and we are pleased to be able to provide access to those who are eligible in the U.K. In France, as Brad also noted, the French National Agency for the Safety of Medicines and Health Products granted the first reimbursed access to AT-GAA under their Compassionate Access Program, formerly known as the Nominated ATU program.
With this growth in our access programs, we're pleased to report that now more than 175 patients worldwide are being treated with AT-GAA across our clinical extension studies and our expanded access programs, and we expect that to continue to grow. For the younger Pompe community, we continue to enroll the ongoing open label study in children up to 18 years of age living with LOPD and expect to expand into patients with infantile-onset Pompe disease, or IOPD, later this year. Importantly, in response to the many requests for treatment that we continue to receive for children living with both LOPD and IOPD, our expanded access programs continue to increase. On slide 17, we just announced today an early-stage program to explore next-generation pharmacological chaperones for Fabry disease through an academic research collaboration agreement with the University of Seville.
This new collaboration will search for innovative small molecules with optimal activity and pharmacokinetic properties. Driven by both the science and the needs of people living with Fabry, we will be reviewing Fabry compounds based on several attributes, including potency, number of addressable amenable mutations, and dosing. Of note, the agreement costs at this point are very modest, and we do not expect our fiscal year operating and will not impact our fiscal year operating expense guidance. With that, I would like to now turn the call over to Daphne Quimi, our Chief Financial Officer, to review our financial results, guidance, and outlook. Daphne?
Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 19 with an overview of our second quarter revenue performance and impacts of foreign currency exchange rates. For the second quarter, we achieved Galafold revenue of $80.7 million, which is a 4.3% increase over the same period in 2021. This includes operational revenue growth of 12.9%, offset by a negative currency impact of 8.6%. Given a majority of Galafold revenue is generated outside of the U.S., we see significant FX exposure to our reported revenue numbers. The euro, the British pound, and the Japanese yen are the currencies our ex-U.S. sales are most exposed to. On a year-to-date basis, these FX rates have declined by 8%, 10%, and 15% respectively.
Applying average July 2022 foreign currency exchange rates, the impact on 2022 full-year Galafold reported sales would be a negative impact of approximately 9% or $26 million. Slide 20 outlines our income statement for the second quarter ending June 30, 2022. Cost of goods sold as a percentage of net sales was 10.2% in the year as compared to 10.8% for the prior year period. Total GAAP operating expenses were $133.1 million in the second quarter, as compared to $107.9 million in the second quarter of 2021. The increase included non-recurring expenses related to the reprioritization of the gene therapy portfolio.
On a non-GAAP basis, total operating expenses were $119.2 million in the second quarter as compared to $93.5 million in the second quarter of 2021. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation expense, loss on impairment of assets, changes in fair value of contingent consideration and depreciation. Net loss for the second quarter of 2022 was $62.2 million or $0.21 per share, as compared to a net loss of $51.2 million or $0.19 per share for the prior year period. At June thirtieth, 2022, we had approximately 280 million shares outstanding.
This year, we expect total non-GAAP operating expenses to be at the lower end of our guidance range of $470 million-$485 million, driven by continued investment in the global Galafold launch and AT-GAA clinical studies and pre-launch activities. As we highlighted previously, this guidance also includes an approximate $70 million related to certain non-recurring costs for the manufacture of AT-GAA to support the global launch, as well as commitments for the gene therapy portfolio. Importantly, in 2023 and beyond, we would expect non-GAAP operating expense levels to decline below levels we saw in 2021. Turning now to slide 21. We continue to operate from a position of financial strength and remain on track to achieve non-GAAP profitability in 2023, as defined in our press release.
We will focus the majority of our investments on our core value-driving franchises in Fabry disease and Pompe disease by continuing to deliver on the global growth of Galafold, securing approvals and launching AT-GAA globally, as well as driving efficiencies, cost savings and careful expense management. A few comments about our cash position and 2022 financial guidance. Cash, cash equivalents and marketable securities were $386.8 million at June 30, 2022, compared to $482.5 million at December 31, 2021. Our full year Galafold revenue guidance is $350 million-$365 million at constant foreign currency exchange rates. In addition to our non-GAAP operating expense guidance of the lower end of $470 million-$485 million.
With that, let me turn the call back over to Bradley for closing remarks.
Great. Thank you, Daphne, Jeff, Sébastien, Andrew, and thanks to all of our employees around the world who continue to work tirelessly for people living with rare diseases. With that, operator, we can now turn the call over to you to open up for questions.
Thank you. Ladies and gentlemen, if you have a question, please press star and then the number one key on your touch-tone phone. At this time, we ask that you only ask one question. If you have additional questions, please enter back into the queue. If your question has been answered or you wish to remove yourself from queue, please press star then two. Once again, that is star then one to ask a question. Our first question today will come from Anupam Rama with JP Morgan. Please go ahead.
Hey, guys. Thanks so much for taking the question. Brad, congrats on ascending to the CEO role. We all knew it's coming, but congrats again, man.
Thank you.
Brad, I've gotten a couple inbounds on your opening comments that perhaps you sounded a little bit more cautious or hedged around the WuXi manufacturing inspection. What is your level of confidence here that the inspection is completed in the near term and we get a timely sort of approval of AT-GAA? Thanks.
Yeah, thanks, Anupam, and appreciate the congratulations. Yeah, look, we just wanted to be very straightforward with where we are with WuXi. We continue to be extremely prepared and with our partners at WuXi to welcome the inspectors in. We're working very collaboratively and are in active dialogue with the inspectors. I think we still have plenty of time for an inspection to be conducted. We just wanted to state, you know, what I guess is fairly obvious that if that doesn't happen ahead of the October PDUFA date, then there is an opportunity then for a delay. Right now, as we said on the call, we remain confident that both products would be approved at the same time and confident that we can hit that October 29th PDUFA date.
Thanks so much for taking our question.
Our next question will come from Ritu Baral with Cowen. Please go ahead.
Good morning. Thanks for taking the questions and congrats, Brad. It's been a long time coming. Glad to see you in the seat.
Thank you, Ritu.
I wanted to ask about the labeling discussions with FDA and how to appropriately frame expectations.
How what you see as the likely label will help you address the Pompe market as you see it. You know, if I can also ask the flip side to that for Europe, I think you guys have the day one 20 questions at this point. How would you answer that? You know, how EMA or CHMP is going down the path of helping you address the broadest possible market and get the broadest label.
Yeah. Thanks, Ritu. Yeah, we are really pleased with where we are with both agencies, and of course, the reviews are separate, although I think the, you know, scenarios you could play out are the same with each. We'll start with the FDA, and I think based on where we are, we are highly confident, and the most important thing is an approval, and we're highly confident that we will have a label that will allow us to be successful in our commercialization of AT-GAA.
I think the most important thing that we're focused on that we've continued to reiterate is that we have what we think is a highly differentiated product, in particular, based on the very compelling data that Jeff reviewed around showing nominal statistically significant improvements in six-minute walk in the switch population, as well as stabilization, of course, vital capacity. Those data have never been seen before in a well-controlled study, and we think those are the most important data to have within the label to be successful. As long as we have those data, and as long as we're in line with where we are with the discussion today, I think we're very confident that we'll be able to address the commercial need and the commercial market for AT-GAA.
I think it's important to remember that, you know, there's roughly 3,200 patients on AT-GAA today. That represents the vast majority of the unmet need in Pompe disease. Based on where we are, we're very confident we'll have a successful label to support those patients. I think in Europe, again, it's a separate discussion, and I think the same, you know, scenarios could play out there. I think the same emphasis is there in terms of making sure that we have those key data in the label. We're confident that the progress there reflects, again, a very successful outcome, and we're eager to conclude that and looking forward to potential approvals at the end of this year and launching early next year.
Thanks.
Sorry, let me just.
Our next question will come. Oh, go ahead.
I was just gonna say, let me just clarify. I think I said last time, 3,200 patients on AT-GAA. It's 3,200 patients on standard of care.
Our next question will come from Joseph Schwartz with SVB Leerink. Please go ahead.
Hi, thanks so much. I was wondering if you can talk a little bit more about the expanded access experience to date for AT-GAA. Are there any unifying characteristics or patient segments that are identifiable here in the adoption to date? Do you think that it's likely that any of these patterns might carry over to the marketplace if and hopefully when AT-GAA is approved?
Yeah. Thanks, Joe. First of all, you know, really excited to have the first reimbursed access for AT-GAA through the Compassionate Access Program in France. I think that's just a really important milestone, exciting and hopefully a bellwether for more to come. You know, I would say there are a few broad buckets of those access programs. Of course, part of it is just our ongoing clinical trial patients who are primarily late-onset patients, who came into our studies in phase II and phase III. The biggest cohort of patients is the EAMS access program in the U.K.
We think that's really important because it's a label that reflects the unmet need in Pompe disease, and it provides an opportunity for patients and for physicians to, I think a completely kind of unaffected way from Amicus. It's not a promotional program, allows them to select going on to AT-GAA. I think that population who are, as Jeff mentioned, required to be on therapy for two years before being eligible for access to AT-GAA. I think that represents the vast majority of the market today and seeing I think a strong preference and strong utilization now more than a dozen patients entering in that program. I think is a great example of what we can see in the future.
We do, of course, also see a variety of patients who are either infantile onset, who are really looking for some opportunity for better outcomes, as well as pediatric and some later-onset patients as well in other markets. I think that just demonstrates, you know, the unmet need that remains out there and the hope that we can provide with AT-GAA, and we're very much looking forward to continuing to be able to serve those markets over time.
Thank you very much.
Our next question will come from Ellie Merle with UBS. Please go ahead.
Hey, guys. Thanks for taking the question. Just a follow-up on the U.S. manufacturing inspection. I guess, you know, when typically in the review cycle would you expect the inspection to occur by? And I guess how long ahead of the October 29th PDUFA would it need to be scheduled by, for you to be confident that it could be completed ahead of the PDUFA? I guess just in terms of, like, you know, the scheduling and how long it would take, you know, once scheduled, just any color that you could give on that. And then just a quick one on Galafold. You mentioned that in June you saw the highest number of net new patients in the U.S., on Galafold.
Is this something that you expect just around seasonality, or is this sort of a broader trend that you expect to continue? Thanks.
Thanks, Ellie. I'll let Sébastien take the Galafold question and provide additional color there. Starting on the WuXi inspection, I think we've said before there are a variety of options the FDA can utilize to support an inspection. There could be paper-based, there could be hybrid, there could be direct inspections from folks from the United States, and we're prepared to support any one of those. We actually know just recently that WuXi supported a virtual inspection, a paper-based inspection from a different regulatory authority. We also know they just hosted the U.S. Department of Commerce who inspected on that unverified list. We know inspectors are able to get in and inspections are able to be conducted.
In terms of timing, you know, don't wanna get too cute there, but I think we just wanna be, you know, fully clear that we're prepared to support an inspection. We're confident that we're poised for approval, but just acknowledge that that does need to happen prior to the PDUFA date in order for the approval to go forward at that point. Then Sébastien, do you wanna address Ellie's question on the U.S. Galafold dynamics and maybe broadly what we're seeing in Galafold?
Absolutely. Thanks, Ellie, for the question. I think that, you know, you asked whether there was some degree of seasonality in what we've seen in the U.S. of late. My answer would be not really. This is more related to the level of activity that we've seen. Clearly our interaction with HCPs has been picking up significantly. You know, when we compare beginning of this year versus beginning of last year, we've seen in some countries almost a tenfold increase in face-to-face interaction. That's having an impact. We're also, you know, a second element that we're seeing in the U.S. is we continue to see an increase in the number of prescribers of Galafold. Unique prescribers of Galafold continue to increase, so we have more physicians prescribing Galafold.
The trend that we've seen over the last few months in the U.S., you know, seems to continue to play here with July. We're in good situation in the U.S.
Great. Thanks.
Our next question will come from Dae Gon Ha with Stifel. Please go ahead.
Great. Good morning. Thanks for taking my questions, and congrats on all the progress. Question from me is on the 2023 financial guidance. Maybe for Daphne. Can you speak to the sensitivity around your 2023 projections of non-GAAP profitability and how the non-GAAP OpEx is being lower than 2021? I just saw the footnote on the press release, where it does kind of talk about the variability and predictability. So just wanted to get a little bit color around that sensitivity. Thank you.
Yeah. Daphne, do you want to address that?
Sure. Thanks for the question, Dae Gon Ha. I think that the comment is really coming from the fact that we have some expenses that we've experienced over the past few years, specifically related to AT-GAA for the manufacture of the product. Once it is approved, that spending will move over to the balance sheet and flow through the income statement and cost of goods sold. There's a large piece of that OpEx that will no longer be there. When we look out into the future, that's the largest piece, I would say, that's driving that commentary. There are also some expenses this year that are non-recurring in nature, as related to the reprioritization of the gene therapy portfolio.
Those are expenses that we have this year that will not occur in the future. It's really related to those two items predominantly is where that comment is coming from.
Okay, great. Thanks so much for the color.
Sure.
Thanks, Dae Gon.
Our next question will come from Salveen Richter with Goldman Sachs. Please go ahead.
Hey, good morning. This is Matt on for Salveen. Could you guys please just give us an update on the Fabry gene therapy program, and then also the next- generation chaperones you mentioned? Thank you.
Yeah. Jeff, maybe I'll start, and then I'll kick it over to you. As a reminder, we continue to have, we think, very differentiated approaches in both Fabry and Pompe gene therapy, and those are still important programs for us. We continue to move those technologies forward, but I think in a very measured and targeted way, given the reprioritization of our program, with the idea that I think there are some broader gene therapy questions we're still looking to answer before we can put those forward into the clinic. I will say, you know, as it relates to the next- generation chaperone, I think that's a reflection of Amicus' commitment to continue to be at the forefront of developing new therapies for anything for Fabry or Pompe.
You know, while it's early, I think it's an exciting opportunity for us there. Maybe, Jeff, you can give a little bit more color.
Yeah. Thanks, Brad. Nothing really to add on the Fabry gene therapy in addition to what Bradley commented on. You know, for that Fabry chaperone discovery collaboration, you know, we're very excited to enter that. It's very early stage. You know, as we have meaningful data, we will, you know, present that at conferences. Right now it, you know, it's really trying to see if there's a way to expand the number of amenable mutations that we could, you know, benefit more patients with a small molecule chaperone. Then just, you know, related to that, see if we can improve some of what we believe is an already very strong profile for Galafold, but to see if there's additional benefit we can bring to Fabry patients through a chaperone.
We will, you know, provide updates as they come.
Great. Thank you. Our next question will come from Kristen Kluska with Cantor Fitzgerald. Please go ahead.
Good morning. This is Rick on for Kristen. Thank you for taking our question. What, if any, effect do you believe the foreign exchange headwinds could have on the 70/30 split that you've talked about in ex-U.S. and U.S. sales as you grow the Galafold business? How are you thinking about this effect as you continue to guide toward expanding into new markets? Thank you.
Yeah, I think as you saw, and I'm getting a little echo on the line, but I think as you saw, there was a slightly greater distribution of revenue coming from the U.S. this year versus ex-U.S. I think it was like 33% versus 67%, which is still near that 70/30, but that just shows the I would say, the slight impact on Europe. I think in general, going forward, we would expect that 70/30 split on average. To your point, as new markets come on, you do see, you know, those will typically be outside the United States, but of course it's all different currencies.
You know, we're not in the business of predicting, FX around the world globally, but I think the most important thing is the growth rates between the two remain strong. We continue to expect significant growth in the U.S., significant growth outside the U.S., and, you know, roughly over time, that should balance out to about 70/30.
Thanks.
Once again, if you would like to ask a question, please press star then one. Our next question will come from Zhiqiang Shu with Berenberg. Please go ahead.
Hi, good morning. Thanks for taking my questions, and congrats on the progress as well. I wanna ask about the EO slide 16. You talked about ongoing support of studies on LOPD and IOPD. Maybe you can talk about the implications there and how that relates to your label discussion? Secondly, just looking at Galafold sales in the first half and full year guidance, considering the negative impacts on foreign exchange, it looks like the second half, they will be pretty flat, considering the foreign exchange. Maybe provide a bit color on that. Thank you.
Maybe I'll take the end of that question first, and then Jeff, you can come back to the development, strategy and how it will impact the label over time. As it relates to Galafold growth, look, you know, we're not in the business of predicting foreign exchange rates, but I think we've just said at, as a point in time, what could the impact be on the actual reported revenue. For us, the most important thing is the underlying business remains strong, remains growing and growing robustly. I think that point that Sébastien made around the 19% growth from this time last year in terms of patients, that's really the business demand, right? That's really how the business is growing and it's growing really strongly and growing right in line with what we said it would.
As it relates to the second half of the year, you know, usually we see a greater distribution of revenue in the second half of the year versus the first half of the year. We are very confident that we will see that. From an operational basis, we're reiterating our guidance of $350-$365. Again, exactly how foreign exchange impacts that is difficult to predict, but for now, we've provided that kind of point estimate for what the impact could be from a reported perspective. Again, for us, the importance is that the business is strong and growing and growing in all key markets, and we continue to anticipate that going forward.
Jeff, do you wanna talk a little bit about the Pompe development strategy, in particular, the different populations late-onset and pediatric?
Yeah, sure. As a reminder, PROPEL was included only adult patients. You know, the vast majority of the data in our initial submissions will be focused on adult Pompe patients, and that would be our expected initial labeling. We do have an ongoing pediatric LOPD study, and we do have agreement with regulatory agencies to do an extrapolation of efficacy, you know, from the adult patients down into those pediatric LOPD patients. We are imminently getting ready to start adding IOPD patients to that clinical trial as well. We do need to look at some measures of efficacy and safety in that IOPD population. We expect, you know, initial labels focused on adults, but then as we have data sufficient to, you know, add in the pediatric patients, we will.
As I noted on the call, we continue to treat multiple pediatric patients, IOPD, LOPD, through expanded access, where there's significant need.
Great. Thank you.
Our next question will come from Ritu Baral with Cowen. Please go ahead.
Hi, guys. Thanks for taking the follow-up. I just wanted to drill down a little more into the U.S. dynamics and the sort of return to growth or growth re-acceleration. I guess I'm surprised that new prescribers are still growing this long into the launch. Also I'm wondering how much mutations play into it. You guys have the number of mutations on the European label in the slides, but how does that compare to the U.S. label and are those still growing, the number of mutations in the U.S. label? Is that driving the growth? Is there like a cap you're about to hit, which triggered the next gen program?
Yeah, thanks, Ritu. Good questions. As it relates to the growth dynamic in the United States, I think it really has more to do with what Sébastien described, which is increasing opportunity for physicians and our sales and medical team to be together. While we did a great job of maintaining those virtual interactions, I think, you know, kind of nothing beats face-to-face. It probably represents also some improved access for patients and physicians and more frequent access for patients and physicians so that physicians can start patients on therapy. You know, whether it's a bit of a new normal or whether it's, you know, some adjustment and ability to now kind of handle COVID in a different way, I think that's really what's driving that kind of resurgence in demand.
I can say that even in July, we're continuing to see great numbers, not just in the U.S., but around the world. Again, that 19% growth rate in patients coming onto therapy from end of second quarter versus end of second quarter last year, to me, that says the business is growing strong, and we continue to expect that. As it relates to the mutations piece, no, you're right.
Remember the really interesting and exciting part about the European label is that we were able to characterize all of the theoretical mutations that could be amenable to the chaperone, and the Europeans accepted that concept of amenability, and we were able to expand the label so that even though not every mutation had an actual patient diagnosed with that mutation, if we find one who does have those mutations, then they can immediately be eligible for therapy. In the United States, it's slightly different. While they fully accept the amenability concept, in order to update the label in the United States, we are obligated to find a patient with that mutation, and then we can subsequently update the label. It's just a little bit of a slower process.
Eventually, you know, presumably we'd find, you know, majority of those amenable patients. As it relates to prescribers, I think honestly, that's just a reflection of the rare disease space where, you know, these patients and physicians. We continue to find new patients. We continue to then have new physicians. And we do continue to see new prescribers come on board, which I think just again reflects the continuing growth opportunity for Galafold. All great positive signs for the business for years to come.
How many mutations are left in the U.S., as you see it, to be included in that label?
Well, I mean, what's the European label, Jeff, and then what's the U.S. label?
Yeah. I think it's, you know, almost 1400 amenable mutations in the European label, and it's, you know, around 350 in the U.S. Look, we continue to add mutations every year as patients and patient families
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Have a novel mutation. We do expect that number will keep going up over time. You know, I don't think it will ever reach the true theoretical rate. As Brad said, it really doesn't limit access in the U.S. It just might cause a slight delay as it might be a mutation that's not in the label. We've already tested them, so we don't have to rerun the assay. We just need to go through the paperwork with FDA to add it to the label.
I see. Thank you.
Thanks, Ritu.
Ladies and gentlemen, this will conclude our question-and-answer session, also concluding today's conference call. We'd like to thank you for attending today's presentation, and at this time, you may now disconnect your lines.