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Intrinsic Value is all-important and is the only logical way to evaluate the relative attractiveness of investments and businesses.
Good day, ladies and gentlemen, and welcome to the Amicus Therapeutics Third Quarter 2018 Results Conference Call. [Operator Instructions] As a reminder, today's conference is being recorded for replay purposes.
It is now my please to turn the conference over to your host, Ms. Sara Pellegrino, Vice President of Investor Relations and Corporate Communications. Please go ahead.
Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics’ third quarter 2018 Financial Results and Corporate Highlights. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer; Bradley Campbell, President and Chief Operating Officer; and Chip Baird, Chief Financial Officer. Dr. Jay Barth, Chief Medical Officer; Dr. Hung Do, Chief Science Officer, and Dr. Jeff Castelli, Chief Portfolio Officer are also here and available to participate in the Q&A session.
On this call, as referenced 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 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 on slide 2 of our third quarter 2018 results slide deck, as well as the Forward-looking Statements and Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2017 as well as our quarterly report on Form 10-Q for the quarter ended September 30, 2018 to be filed tomorrow, November 6, 2018 with the SEC.
At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics. John?
Great. Good morning, everybody and thank you Sara and Sara, it’s nice to have you back from your maternity leave. Nice to see the Amicus family expanding in many ways. This is our, of course, third quarter results conference call this morning where I’ll begin the discussion on slide 3 with a snapshot of Amicus today, following a period of major transformation for the company in the last quarter.
Over the last three months, we had a number of accomplishments, including we received our first ever US drug approval for Galafold, we also expanded our pipeline to now include 14 new gene therapy programs for rare metabolic disorders and we also presented positive 18-month data for our differentiated Pompe enzyme replacement therapy. I absolutely believe that in this time of growth, Amicus has never been in a better position to drive value for patients and for shareholders alike. And with the strength of our balance sheet now more than $560 million in cash on hand, we are in an excellent position to invest in our entire current portfolio.
Let me turn to slide 4 and I'd like to briefly summarize the four key areas of emphasis on today's call. First, Galafold. Galafold’s global momentum continues both internationally and in the United States, as demand and usage of Galafold continues to grow. While the timing of orders was more variable this past quarter, we remain fully on track to achieve the higher end of our full year 2018 guidance range.
Also, following the FDA approval in August of Galafold in the United States, our US launch continues to significantly exceed our own expectations and sets a very strong foundation for 2019 and beyond. We continue to believe that Galafold has more than $500 million in peak revenue potential and it is the cornerstone of our success to fund one of the leading rare disease portfolios and are the engines in biotech.
Second point to emphasize on today's call is the most recent positive dataset for our lead Pompe, I'm sorry, our lead pipeline program, AT-GAA, which continues to support the potential for AT-GAA to become the future standard of care that transforms the entire Pompe treatment paradigm. We very much look forward to enrolling initial patients into our pivotal study, which we have named the PROPEL study by the end of this year.
Third key point today, we will briefly recap the highlights of our new gene therapy pipeline covered in great detail during our recent Amicus Analyst Day in New York on October 11 and which featured key external speakers, including Dr. Kathrin Meyer of Nationwide Children's Hospital in Columbus, Ohio and also Dr. Jim Wilson of the University of Pennsylvania. Our 14 new programs together have the potential to impact at least 10,000 additional persons living with rare metabolic diseases, mostly all children and we could not be more excited about the potential for these R&D platforms to drive significant future growth and we believe $1 billion plus in recurring peak revenue for Amicus from this gene therapy portfolio that we've now assembled.
And finally, fourth, I’ll reiterate again that we are very well capitalized to advance toward our 2023 vision to treat at least 5000 patients and to achieve $1 billion in global revenue. Our current cash is sufficient to fund operations into at least 2021 without any immediate need to raise additional capital and we remain prudent in our investments, our hiring and our overall business operations. As we mentioned in this morning's press release, through judicious financial management, we have reduced our full year cash spend guidance now down to $190 million to $210 million. Chip will cover our financials of course in more detail, but the key takeaway is that we are well capitalized to invest in our future success, while being mindful of the impact of dilution on our shareholders as we continue to build a leading global rare disease biotechnology company.
So with that overview, let me turn the call over now to Brad Campbell, our President and Chief Operating Officer to highlight the success with the Galafold launch. Brad, please.
Great. Thanks, John. Good morning, everyone. Let me begin on slide 7 where we go through a snapshot of the Galafold launch through September 30. We're very pleased with the progress for Galafold this year, including the launch into new countries such as Japan, United States and most recently Australia, bringing the total number of reimbursed markets for Galafold to 22 countries around the world. Our third quarter revenue was $20.6 million, a year over year increase of approximately 98% from the third quarter 2017.
As we discussed at our Analyst Day in October and mentioned in our press release this morning, sequential revenue growth was impacted by uneven ordering patterns in Europe, which I'll discuss further in a moment. As we come now to the fourth quarter, we know already that ordering patterns will stabilize, relative to third quarter and the US launch continues to exceed expectations, along with great progress in Japan as well.
So we're firmly on track to come in at the higher end of the $80 million to $90 million full year guidance range, which as a reminder represents more than double our revenue from last year. And importantly, our vision of offering the first ever pharmacogenetic approach to treating Fabry patients with amenable mutations or gene variants as they’re described in the US label has become a reality now with nearly 100 new mutations added to the European label since our initial approval, 269 initially versus 367 today and now 348 amenable gene variants in the US list.
Turning to slide 8, let me share a little bit more detail on our international progress. We've continued to see very strong penetration throughout Europe and now have more than a 50% market share of treated amenable patients within the EU5 countries, which represents the lion's share of the European Fabry population. Importantly, in the more mature markets like Germany and the UK, the market share is well north of 50% of treated amenable patients and we continue to see future growth opportunities in these initial launch countries, as we begin to see increasing portion of diagnosed, but untreated patients come on to Galafold.
So not only are we continuing to see a high number of switch patients, we're also now growing the market by bringing these untreated patients on to therapy often for the first time. We expect to see that pattern continue in our newer markets as well, early adoption from switch patients and then continued uptake in the diagnosed untreated patients, which again represents a significant long term growth opportunity.
And across all markets, we continue to see an extremely high rate of compliance and adherence to this oral treatment regimen and finally, as we alluded to at our Analyst Day in October and in the third quarter, we started to see uneven ordering patterns that are relatively new to this market. For example, as adoption continues with very high adherence and compliance rates, we're seeing a shift in some of the larger markets from one month to three month prescriptions, particularly heading into the summer months.
While this can create uneven ordering patterns, we think of it almost as a positive new reality for patients with an oral treatment option that offers the ability to stock up in advance of summer travels and holidays. Coming in to the fourth quarter, ordering patterns have generally normalized and we're expecting a very strong finish to the year.
And moving on to slide 9, let me touch on the progress with the launch in the United States, which is going extremely well. As of October 31, a total of 103 patients have been prescribed Galafold in the United States based on our tracking of patient referral forms or PRFs, which we introduced as a key metric at our Analyst Day in October. This demand significantly exceeded our initial launch forecast, which was based on the successful launch in Germany. So this graph illustrates the point, as we built our US forecast, we plotted our German launch there against the US market dynamics, which predicted approximately 66 PRFs after four months of launch here in the United States.
And what you can see is that, as of October 31st, we're well ahead of that initial forecast, with again 103 patients now prescribed Galafold. And this comes from a broad prescriber base of more than 40 physicians, includes conversion of all 25 of our study patients and includes a significant number of new non-study patients as well. And just as a reminder, as we highlighted at our Analyst Day in October, given the approximately 60-day average time from PRF to shipment of drug, while this will set a very strong foundation for 2019, we will see limited revenue impact in 2018.
Finally, turning to slide 10, let me just reiterate that we are on track to achieve the higher end of our full year guidance range of $80 million to $90 million. We're confident in our ability to achieve this objective based on the international growth dynamics that I just outlined as well as the launch success in the US and Japan and the continued enthusiasm from the team and from the Fabry community.
With that, let me turn the call back to Chip to provide an update on our financials.
Thanks, Brad. Good morning, everyone. Our financial overview begins on slide 12 with our income statement for the three months ending September 30, 2018. For the third quarter of 2018, we recorded Galafold revenue of 20.6 million. Cost of goods sold included manufacturing costs as well as royalties associated with the sales of our product, cost of goods sold as a percentage of net sales was 20.9% for the three months ended September 30, 2018 as compared to 16.5% for the year ago period. We continue to make significant investments in R&D, as we continue on our vision of building one of the leading global rare disease biotech companies.
During the third quarter of 2018, we recorded 138.3 million in R&D expense, which includes the upfront payment of 100 million for the Celenex asset acquisition. This compares to 40.6 million for the prior year period. Importantly, if we have this upfront payment year-over-year, R&D spend would have been slightly lower in 3Q18 than 3Q17.
Moving down the income statement, total selling, general and administrate expenses in the third quarter of 2018 was 31.9 million as compared to 21.6 million for the prior year period. The increase represents the expanded geographic scope of the ongoing Galafold commercial launch, including additional launch activities in Japan and the United States. Net loss for the third quarter of 2018 was $459.2 million or $0.84 per share compared to a net loss of 111 million or $0.69 per share for the prior year period. Net loss, excluding the one-time Celenex acquisition expense was 59.2 million or $0.31 per share. And as of September 30, 2018, we had approximately 189.2 million shares outstanding.
Moving on to slide 13, a few comments about our current cash position and 2018 financial guidance. Cash, cash equivalents and marketable securities totaled 564 million on September 30, 2018 compared to 359 million at December 30, 2017. Looking at the remainder of the year, we are reaffirming our full year Galafold revenue guidance at the high end of the $80 million to $90 million range, reflecting the continued success globally. In addition, we are updating our 2018 full year cash spend guidance to 190 million to 210 million, a $30 million favorable shift on the range due to careful management of our investments, hiring and overall operations.
With our current cash position and the continued ramp we see for the Galafold launch, we have sufficient capital to fund our ongoing operations into at least 2021. And as we've noted in the past, potential future business development collaborations, pipeline expansion and investment in manufacturing capabilities could impact future capital requirements.
This summarizes our key financials for the third quarter. Additional details can be found in our quarterly report 10-Q, which will be filed later today. I’m happy to answer any questions during the Q&A, but for now, we’ll turn it back to John.
Great. Thank you, Chip. I’ll now highlight our very exciting Pompe program, beginning on slide 15 with a recap of our 18 month Phase 2 data for AT-GAA, which continued to show consistent and durable responses across key measures of safety, functional outcomes and biomarkers in both ERT switch and the ERT naïve Pompe patients out to month 18. We continue to believe that these data are remarkable.
The functional assessments that we have shown with this data that these data show that patients who are able to walk can walk farther and patients who are in wheelchairs have better movement in their arms and shoulders. These data were presented in detail at the World Muscle Society Congress as well as our Amicus Annual Analyst Day in early October by Dr. Mark Roberts from the United Kingdom. For those who did not hear these presentations, I would encourage you to view the slide presentation and the webcast replay on the Amicus website.
Turning now to slide 16, I'd like to emphasize the enormous progress we have made in 2018 with respect to our clinical, regulatory and manufacturing activities in this Pompe program. We remain fully committed today more than ever to advance this program, so that AT-GAA is available to as many people living with Pompe disease as absolutely quickly as possible. To do so, we are gathering a robust data set from our ongoing studies and upcoming pivotal study.
As you can see from our set of clinical activities, we have announced the additional 18 months data from our Phase 1/2 study. We've also enrolled an additional cohort of switch patients into this phase 1/2 study and by the end of this year, we expect to finish a retrospective natural history study of patients on the approved ERT to give us context for all of these data that we've been able to see. We are on track to enroll initial patients into the Phase 3 for [indiscernible] study by the end of this year to support full approval in the United States, the EU and other major geographies.
In manufacturing, we have successfully scaled to the 1000 liter commercial scale and that 1000 liter material has been released for all patients to be treated in the upcoming PROPEL pivotal study. I cannot overemphasize the importance of our manufacturing strategy and success to date in scaling up GMP supply at this commercial scale with this commercial material in advance of our pivotal study and that we have already reached an agreement on via comparability with key regulatory authorities in the United States and in Europe.
Finally, on the regulatory front as a reminder, both the European Medicines Agency, EMA in Europe as well as the US FDA have been encouraged by the data for AT-GAA and they have specifically acknowledged the significant unmet need that remains in Pompe disease. The regulators have advised as though that the current data package are not sufficient at this time to support an early approval. We are laser focused on doing what we need to do to further build out our body of data for AT-GAA.
And while we engage with regulators throughout the process, our base case, as we've stated before, is to conduct the pivotal PROPEL study to support full approval in the US, the EU and other major geographies. We do not expect to provide any additional regulatory update in 2019 or otherwise following on these continued interactions with regulators during the normal course of the Phase 3 pivotal program. Unless there is any change to this base case scenario, the next regulatory update in your models should be the end of Phase 3 meeting, after we have the data from the pivotal study.
Moving to slide 18, I'd like to highlight what we believe to be the leading gene therapy portfolio in lysosomal storage disorders or LSDs. Through our asset acquisition of Celenex and our collaboration with UPenn, we are combining best-in-class gene therapy technologies and capabilities together with our Amicus expertise in development and commercialization of new medicines for the lysosomal disorders. We now own full global rights to 14 new gene therapy programs that we did not own three months ago and the combined opportunity across these 14 diseases, I'm sorry, across just 10 of these diseases has the potential to impact at least 10,000 additional people living with these life threatening conditions, which based on the Celenex acquisition of those 10 gene therapy programs we believe could translate to $1 billion in peak recurring revenue.
Within this gene therapy portfolio now, turning to slide 19, we have three potential first in class therapies for three different types of baton disease, which have demonstrated compelling proof of concept following a single AAV intrathecal administration. The CLN 6 and CLN3 programs are clinical stage and are the first programs to enter the clinic for these devastating diseases.
In the CLN3 program, we expect to dose the first patient by year end. We have seen preliminary clinical data for the CLN6 program and to date the CLN3 and CLN8 programs have shown definitive pre-clinical efficacy. Again for those of you who didn’t view our Analyst Day presentation by Dr. Kathrin Meyer of Nationwide Children’s, I invite you to take a closer look at our slide presentation and webcast available on the Amicus website. We are very excited about these programs and we look forward to reporting additional clinical and pre-clinical data throughout 2019 across our gene therapy programs for neurologic lysosomal storage disorders.
Now, as outlined on slide 20, our relationship with the University of Pennsylvania will combine Amicus’ protein engineering and glycobiology expertise with Penn’s AAV gene transfer technologies to develop AAV gene therapies designed for optimal cellular uptake, targeting dosing, safety and manufacturability for four indications. Again these are for Fabry disease, Pompe, CDKL5 deficiency disorder and one additional rare metabolic disorder.
In Pompe, we have shown early proof of principle for Amicus DNA constructs for an optimized gene therapy to address all aspects of Pompe disease including the central nervous system, heart and muscles. And in Fabry disease, early proof of principle for Amicus DNA constructs were shown for an optimized gene therapy to deliver stable, active enzyme to lysosomes.
In closing then, on slide 22, I'd like to reiterate that we are on track to achieve all five key strategic priorities outlined at the beginning of the year. And on slide 23, the Amicus vision remains the same, as it was as I showed at the beginning of this year to treat at least 5000 patients and to achieve at least $1 billion in revenue by the end of 2023. We have made significant advancements toward achieving this vision through the strength of the Galafold launch, the dataset and the course ahead in Pompe and the new pipeline programs that we have, as we build a leading global biotech company focused on rare metabolic disorders. Throughout 2018 and along the way to this 2023 goal, we are well positioned to create significant value for patients and for shareholders.
So with that operator, we can turn to the Q&A session of this morning's call. Thank you.
[Operator Instructions] Our first question comes from Anupam Rama of JPMorgan.
Just wondering about that 60-day time to shipment here in the US. Can you talk about if there are any potential efficiencies overtime that can be gained here to decrease that time to shipment?
Sure, Anupam. I’ll let Bradley take that.
You're exactly right. This is really just a pattern we would expect to see in the early days before all the major payers have Galafold on their policies. As you would go forward, you would expect to see this to shrink considerably. That process can be sort of a three to six to nine month process to get on those policies, so we do expect that to slim down really going into 2019.
Our next question comes from Ritu Baral of Cowen and Company.
My first question just focuses on the prescriber and patient base in the US. You guys mentioned you've got 40 plus prescribers. What's the targeting strategy right now? Are you looking at centers, types of patients, can you talk about how you're targeting the prescribers and then also if there's a pull from patients that you're seeing or is it mainly prescribers that are sort of pushing this out to appropriate patients?
You hit on a really important point. In Q3, while we're obviously very excited to be able to get this medicine to many more patients than we expected in the early days of this launch, what's perhaps most exciting in terms of what the potential may actually be in the United States is the fact that we've seen such a wide prescribing base with more than 40 doctors writing prescriptions for those 103 patients. We think that gives the real opportunity for driving this medicine to potentially many more patients.
In terms of the dynamics that we're seeing, push and pull, let me ask Brad to comment on the market dynamics.
Thanks, John. So I would say it’s both in the United States and that's something you might recall Ritu that we've talked about a little bit coming into the launch, which is first of course, you are focusing on KOLs, on physician education and outreach, both for medical affairs and from the sales team, but you also have an ability to interact directly with patients in the United States. It’s of course – you have to be within the regulations, which we will be, but you do have an ability to have an educational conversation with patients and because in the US in particular, there are at least as many diagnosed, untreated and perhaps even more diagnosed untreated patients than there are treated patients, we think the long term opportunity in the -- that untreated population could be very important.
And just going back to the first part of my question, that 40 clinician prescriber base, can you talk a little bit about that makeup and what's your final sort of number of targets?
Sure. So in the US, all in probably 200 to 250 physicians make up the lion's share of the prescriptions. There are some sort of ones and twos out there, which we will cover, but the focus in terms of the broad prescriber base is again 200 to 250, and within that of course, you have the key opinion leaders of which there are probably 40 or 50 total KOLs in the US. So you can already see that we're doing a great job, getting to that initial group of KOLs and we're well covered to get to the broad group of prescribers here in launch.
And my follow up I promise has only one part. Can you talk a little bit about what constitutes optimized constructs, as you see them in Pompe and Fabry, you mentioned that, but as you go towards your final construct, what's most important to you in these two diseases?
I think it’s different for each Pompe and Fabry. Hung is with is. Let me ask Hung if he can comment.
Sure. Thanks, John. Yes, Ritu, what we're trying to do is basically develop ways in which we can increase the expression and secretion of our proteins at the same dose or even at a lower dose. That's kind of our goal and as well as develop proteins from those constructs that are much better targeted or more stable for these diseases. So again, the idea is to leverage our expertise with that to really deliver very effective gene therapies for these diseases.
In contrast to like better secretion, et cetera.
Well, that is part of the construct. It actually delivers both better expression and better secretion and targeting.
And the key really the differentiator for what we're developing and the difference in targeting of the GAA protein again targeting to the all key tissues and organs of disease and also mindful in Pompe in particular, Ritu that it is both a motor neuron disorder and a neuromuscular disease. So you've got to target the CNS and you've got to target the muscle and that’s what we're trying to achieve with our Pompe program and that's where I think our many years of experience in Pompe in the science and the drug development and now combining our protein engineering or glycobiology experience together with Jim Wilson’s experience in his lab at UPenn for designing optimized vectors that it could be a very, very promising approach for people living with Pompe. So certainly something that we are absolutely going to put a significant amount of resources together in our partnership now with Dr. Wilson’s lab, so we expect more data now throughout 2019 on that program as it rapidly advances.
Our next question comes from Joseph Schwartz of Leerink Partners.
So first question that I have is on the Galafold launch in the US and it looks very strong, I was wondering if you could highlight for us what the main drivers of upside have been and if you think that they'll be sustained going forward? You obviously had a lot of experience in Europe and devised a thoughtful forecast and have exceeded that, so it would be helpful if you could give us some insight into what the main drivers of upside have been and is this expected to be a bolus that you will anniversary or do you think it will carry on?
Yeah. I’ll turn it again to Brad at the moment, but I think important Joe to step back and realize that people living with Fabry in the United States and the physicians who treat them have only had one option for 15.5 years and for patients with the medical mutations, they now have a new treatment option, a new paradigm for the treatment in Fabry and that's very exciting for physicians, for patients. It took some time to develop this medicine as we know and to get approval in the United States, but with that time, we think we have a significant dataset in the label in the United States that we think could lead to a very continued, sustainable and significant growth and uptake here in the United States and while early days and I think another quarter or two will really help set the trend line here in these first 12 weeks of launch, again, a couple of key dynamics that give us confidence that this could be an enormously successful launch in the United States and a product with significant momentum.
Brad, I’ll let you kind of reemphasize some of those dynamics that give us that confidence.
Yeah. Thanks, John and thanks, Joe for the question. I think John hit on all the key things, I would summarize by saying we had the successful launch in Europe, so all the learnings there in terms of what were the important education points, what were the important responses to competitive pushback, et cetera that they’d be focused on which patients first was key, so the strategy was really well laid out and well formed. We were able to hire an incredibly experienced team here in the United States and one that I think has done a fantastic job so far. We have, of course, as John mentioned, the downside of taking longer to get approved than we would have hoped, there is lots of time for education and awareness and we had a pretty broad experience base here in the United States whereas you'll recall in Germany, we had no clinical trial sites.
Here in the US, we had 20 or so clinical trial sites. So lots of time to educate. And then I think our reimbursement strategy has really resonated, excuse me, with the payers here in the US. We reminded folks or I’ll remind you that we mentioned at Analyst Day that we have both private payers as well as government reimbursement going on here in the US. So I think that solid reimbursement strategy, that is off to a strong foundation and we again are excited for the end of the year and excited for the strong foundation of sales for 2019.
And again, yeah, just to add one last piece to that, something that also gives us confidence that this could be very sustained in the quarters and years ahead is the nature of Fabry disease and the growing rates of diagnosis through newborn screening, again remembering that this is an X Linked disorder, so you diagnose a child on a newborn screen, you may not treat that child and in our label of course, we're not -- it's not prescribed for children, but you can diagnose a family and in many, many, many cases now, we've seen newly diagnosed, not just individuals, but families living with Fabry disease and typically with very high rates of amenability in those newly diagnosed families. So much, much more work to do on the development to try to identify as many people living with Fabry as possible who may benefit from this new medicine.
And then on your newly acquired gene therapy assets, with Celenex, I was wondering if you could just give us some more insight into how you're thinking about prioritizing those and how many more can a -- how many candidates can you realistically advance simultaneously and when might we get some insight into those whose identity is -- and targets have not been disclosed yet?
There are great efficiencies in leveraging our drug development expertise here at Amicus, Joe, together with the science expertise for the Celenex program at Nationwide Children's and for the Pompe, Fabry and CDKL5 deficiency disorder programs if you can. So very different than the world events on replacement therapies, how we’ve thought about the timelines, the manufacturing and all of that. So we think we can be very aggressive in developing multiple programs.
We will have more to say at the beginning of 2019 about timelines for some of these programs, key activities, but I think what you'll see in 2019 is a tremendous amount of data coming out of the science efforts in both the neurologic program that we have those 10 programs nationwide together with the programs that you can, as you saw, this was -- we didn't begin with just a simple blank sheet of paper for instance with our collaboration with Jim Wilson, we’ve spent a better part of the year thinking through and working on the science, the approach for example, the DNA construct in Fabry and Pompe that Hung was able to put together are already now in Dr. Wilson’s lab and advancing to the next stage of development.
So much, much more to come, but we're really optimistic that we can take these programs, quite a few of them forward in parallel and it really fits with the mission of the company, you look at these neurologic, lysosomal disease programs in particular that are devastating in time is of the essence. These families cannot wait and that’s certainly something that we try to live every day here at Amicus.
Our next question comes from Mike Ulz of Baird.
Just for the Pompe program, you mentioned you're on track to start the Phase 3 PROPEL study later this quarter. I'm just curious if there's a remaining hurdle there and what that is?
And then maybe secondly, just with respect to the natural history data, you’re also on track to complete that by the end of this year, just if you can give us a sense of when we should expect the data and what might be included in terms of patient numbers, time point, is it 6 months.
Yeah, Mike. Just with respect to the first part of the question on PROPEL, there are no other gating items, regulatory manufacturing, US, Europe, everything is lined up. It’s now just initiating the sites and enrolling patients. We’ve got quite a queue of patients for this study as well and again, we expect the first patients enrolled here quite imminently.
And then with respect to the natural history study, we expect that to be complete here by the end of this year and we’ll share that we would expect in the first half of next year.
Your next question comes from Salveen Richter of Goldman Sachs.
I have a couple of quick questions. One of them is, you mentioned that the number of amenable limitations can be treated with Galafold has increased, and I’m wondering how may more do you think there are and how does it translate into patient population, like is there basically an expectation that you may be able to start treating certain percentage more patients as the number of mutations are being more sort of prescribe.
And another one, just wanted to ask about in [indiscernible]
Sure. So let me just begin, I’ll begin and then I'll ask our Chief Portfolio Officer Dr. Castelli to comment on the Fabre mutations and the potential to help more patients there. Again we've estimated in the major geographies in the world that 35% to 50% of people living with Fabre disease have one of any number of amenable mutations and in these early days of the launch with the currently diagnosed patients, that's what we're seeing. It ranges from currently diagnosed patients, north of 50% for instance in the United Kingdom, with some family mutations in the UK and in most countries, Japan, Germany and others, you're seeing 35% to 40% seems to be holding. What is different though is new populations, new families are being diagnosed with Fabry disease, you do see a higher prevalence of those families having amenable mutations.
I’ll ask Dr. Castelli Jeff to comment on why that is?
Sure. Thanks, John. When you look at Fabry disease, basically where there's higher rates of diagnosis, we're seeing greater rates of amenability and that's largely due to the fact that late onset Fabry, when we've looked nearly all are amenable. So basically, we're going into countries, we see that in those countries as doctors go through their records or finding new mutations that we currently hadn't compiled, so we would say today as John mentioned anywhere from 35% to 50% of patients in a given country, where we've looked are amenable, we do expect that in a given country as diagnosis improves, that rate of amenability within a country will also continue to increase over time. So while that's 35% to 50% today, that range could continue to go up across the board in all countries with better diagnosis.
To give an example, since we launched in the middle of 2016, in Europe, we launched originally with 269 amenable mutations in the label and as we've gone out and found new patients as doctors have looked for amenability to Galafold around the world, we've actually been able to increase that label in just 2.5 years from launch in Europe from the original 269 mutations. We've added now more than 100 new mutations that are amenable to that label.
And just a quick question about the enrolment progress in cohort 4.
Yeah. Cohort 4, we’ve enrolled patients in that study. We expect patients to continue to enroll over the next month or so. That enrollment will end by the end of this year and then all patients who present would go into the pivotal study. Most of the patients in the queue today are lined up with the pivotal study though. There's a much narrower set of sites and a much narrower -- more narrow inclusion criteria for that cohort 4.
Our next question comes from Mohit Bansal of Citigroup.
Thanks for taking my question and congrats on solid execution so far on Galafold US launch. Can you just help me understand a little bit these 100 patients who have been referred so far? What percentage of these patients are future versus naïve and in terms of severity of the disease, is there any pattern you are seeing which is different or similar to so far what you have seen with Europe?
Yeah. Thanks, Mohit. Brad, go ahead please.
Yeah. Great question and really this follows the pattern that we've seen in our international launch markets. So our strategy has been to focus on switch patients first. They're the ones that are coming in regularly for their infusions, they are in the system, they're seeing their physicians more regularly or healthcare provider more regularly and we've seen that dynamic play out here. However as we’ve talked about, there is a significant long term growth opportunity in the diagnosis -- untreated patients and I can tell you that there is a small number of patients within that hundreds that were diagnosed and untreated, which is exactly on strategy. We would expect that number to grow over time as the launch matures.
In terms of your point of severity, we know that it's about half males and females in the United States that make up that 100 and we have seen in other markets that we typically see a mix of classic males later on to males and females and we think those demographics are holding here as well. So, so far, we're very much on strategy and very much along the lines of the patterns we've seen in our other very successful launch markets.
And then if I may ask a follow-up, so in terms of – when I spoke to a couple of doctors, they mentioned that most of the symptomatic patients are on treatment, but in some places, they are not on treatment right now, but given that that is the long term strategy, could you, in your market research, could you help us understand from that if there is any pattern there why any symptomatic patient would not go on an ERP right now and how do you plan to welcome those challenges in long term?
Sure. So without getting into specifics, I think the answer is the research we've done and what we've seen in other markets is it really ranges. The data that we see says that actually at least half of diagnosed untreated patients are symptomatic and so I think that's an important point to raise. And when we’ve done market research with patients and physicians to understand why they may not be on therapy, it could be a whole host of things from access to an infusion clinic to age to their particular family dynamic and so obviously it's up to the physician and the patient to determine whether or not it's appropriate for them to come on to treatment, but we very much believe that over time, we could see market growth with more diagnosed untreated patients coming on to Galafold.
Thank you. Ladies and gentlemen, this concludes today's question-and-answer session. I would like to turn the call back over to John Crowley, Chairman and Chief Executive Officer for any closing remarks.
Great. Thank you, operator. So hopefully, you can see what we've accomplished in the last quarter, but we're focused on accomplishing by the end of this year and I think it lays the foundation for what could be an extraordinary 2019 for Amicus. So much work ahead of us and we are going to get back to it. Everybody have a great day. Thank you.
Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program and you may now disconnect. Have a great day.