Sara Pellegrino - Senior Director, Investor Relations John Crowley - Chairman of the Board and Chief Executive Officer Bradley Campbell - President and Chief Operating Officer Hung Do - Chief Scientific Officer Dipal Doshi - Chief Business Officer and General Manager of Scioderm, Inc. William Baird - Chief Financial Officer.
Ritu Baral - Cowen Anupam Rama - JPMorgan Joe Schwartz - Leerink Partners Roy Buchanan - Janney Montgomery Salveen Richter - Goldman Sachs.
Good day, ladies and gentlemen. And welcome to the Amicus Therapeutics first quarter 2016 results conference and webcast. At this time, all participants are in a listen-only mode. Later, we will a conduct a question-and-answer session and instructions will be given at that time. [Operator Instructions] As a reminder, this call is being recorded.
I would now like to turn the call over to Sara Pellegrino. You may begin..
Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics first quarter 2016 corporate highlights program update and financial results. Speaking on today’s call, we have John Crowley, Chairman and Chief Executive Officer; Chip Baird, Chief Financial Officer; Bradley Campbell, President and Chief Operating Officer; Dr.
Hung Do, our Chief Science Officer; and Dipal Doshi, our Chief Business Officer and General Manager of Scioderm. Dr. Jay Barth, our Chief Medical Officer, is also here and available to participate in the Q&A session.
On this call, 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 wells as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that 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 statement, which speak only as 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 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 statement on slide two of the slide deck as well as to the forward-looking statements and risk factors sections of our annual report on Form 10-K for the year ended December 31, 2015 which is filed with the Securities and Exchange Commission.
At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics..
Great. Thank you, Sara. And good morning, everybody. I’m pleased to host this call today on the heels of a very successful first quarter at Amicus. As we’ve discussed before, we have outlined four key strategic priorities focused on our three lead clinical programs and we’ve made significant progress with each one during the first quarter.
The number one priority was getting migalastat approved in the EU as quickly as possible for all Fabry patients with amenable mutations.
As we announced a few weeks ago on April 1, we have received a positive CHMP opinion, recommending full approval of migalastat with a broad label for Fabry patients with amenable mutations, of which the current label lists 269 mutations that today represent approximately 35% to 50% of the total Fabry population.
This was the broadest label that we could have hoped to achieve. And I can tell you, having just returned last week from the commercial launch meeting with the Amicus team in Germany, we are fully prepared to market migalastat to patients in the European Union upon final EC adoption, which we continue to expect in the second quarter.
Brad will go into more detail about the launch plan, but I am extremely pleased with the very high caliber and passion of our team and the preparations that have gone into this launch planning to strongly position Amicus for success in the Fabry market.
Our number two priority is determining the optimal path forward for migalastat here in the United States. We remain fully committed to trying to identify an optimal US pathway based on our existing data set without the need for another Phase III study.
On that front, we have now substantially completed the integration summary of safety analysis as requested by US FDA.
We have also collected and analyzed additional histopathology data and gastrointestinal symptom data, as well as longer-term renal and cardiac data across both Phase III studies, which were presented at the March WORLD meeting in San Diego.
We've not yet disclosed these data with FDA, but we received positive feedback from physicians at the WORLD meeting and, of course, in the CHMP's proposed label. I’ll also add that the CHMP conducted an in-depth and rigorous review of both Phase III studies in reaching its opinion with respect to migalastat.
We’re now finalizing the briefing documents for FDA and we anticipate having a meeting with FDA by mid-year to clarify the US regulatory pathway for migalastat. We currently plan to provide an update on the US regulatory pathway following receipt of formal minutes in the agency event meeting.
We continue to believe that this medicine, migalastat, should be commercially available for all amenable Fabry patients in the United States and we will continue to collaborate with FDA to identify the most rapid path to approval. Our third priority, obtaining important early clinical data for a novel Pompe ERT also remains on track.
We were very excited to report in our press release this morning that we are actively enrolling patients across multiple sites and that patient dosing with this novel ERT, which we refer to as ATB200, is underway for our Phase I/II clinical study of this drug for Pompe disease.
These initial patients have switched from Lumizyme to our ERT, ATB200, which again is highly phosphorylated ERT with optimal glycosylation to deliver what we hope to be significant benefits to patients with Pompe disease with such an extraordinary unmet need still remains.
As a reminder, this proprietary ERT in Pompe is enhanced with the co-administration of a pharmacological chaperone. I’ll review more about this study in an update in the coming part of this call, but I’ll state here that we are very pleased to be dosing patients and remain on track for interim data by year-end.
Finally, we continue to make good progress on our fourth important priority, the successful execution of the Phase III study in EB for Epidermolysis Bullosa. Since the acquisition of Scioderm, we have added significant resources to augment the Scioderm team’s efforts.
We’ve applied our successful global clinical operations expertise in the rare diseases to open new clinical sites globally. Through our strength in medical affairs, we have enhanced our presence within the physician community at key dermatology meetings and we continue to strengthen our collaborative relationships with the EB patient community.
Indeed, we have made significant progress in execution as it relates to these four key strategic priorities and we very much believe that these three clinical programs – in Fabry, Pompe and EB – each with a potential $500 million to $1 billion in potential market opportunity, will be the cornerstone of a much stronger and bolder vision at Amicus to build a leading global biotechnology company focused on rare and devastating diseases.
I’ll refer you, if you have the slide following along here, now to slide four.
As you see here highlighted, we have transformed Amicus over the past few years through the development of our internal pipeline including our chaperone technology with technologies and, importantly, biologic capabilities that we have acquired through the acquisition of Callidus Biopharma as well as our expansion into rare and devastating diseases beyond lysosomal storage disorders with our acquisition of Scioderm in the EB program.
And in 2016, we expect this to be a very important year that has already brought to us the most important achievement so far in our company's history, the positive CHMP opinion for migalastat.
Before I turn the call over to Brad to discuss in more detail our launch plans for migalastat, let me highlight on slide six, the strength of the broad label recommended by the CHMP, and emphasize why this is so significant. This is the first oral therapy for Fabry.
It was recommended by the CHMP for full approval as a first-line therapy and it represents a very innovative use of personalized medicine for patients with amenable mutations in Fabry. Also, two, you’ll see that it is for all patients with amenable mutations, 269 mutations listed in the label.
These amenable mutations, covered in the label, represent 35% to 50% of the diagnosed Fabry population today in a market that generated $1.2 billion in global sales in 2015 and which continues to grow at a double-digit rate annually as new patients are diagnosed.
The label also includes the first-ever searchable Web site for pharmacogenetic medicines where physicians will quickly and accurately determine if a Fabry patient has an amenable mutation. So, again, a real advancement here for migalastat and we believe in the field of medicine.
Having just spent time with our commercial team in Europe last week in preparation for our migalastat launch, I can tell you that they are very excited. This is an extraordinary team and they are committed to this program. Very excited about the strength of this label as we prepare to introduce migalastat into the market in Europe.
I am extremely grateful for the ongoing support, especially from the Fabry community, in particular, those patients – those physicians who led the clinical studies in migalastat as well as the patients who volunteered to these studies over the past decades.
In many cases, giving up access to an approved therapy to switch to a then-unproven technology. We believe that we are well-positioned for success. And with that, I will turn the call over to Bradley to discuss our preparations now for launch in the EU. .
Thank you, John. As John mentioned, we truly are launch-ready at this point and the international team is eager to begin marketing migalastat as soon as we receive formal EC adoption, which we expect in the second quarter. Let me provide a little bit more color there.
Under David Allsop’s leadership, we built a team of over 50 people to support our EU and rest of world launch, including country managers and medics in the major markets in Europe and heads of all of the key commercial and G&A function.
These individuals have significant experience in leading rare disease companies and launching rare disease products and have already done an excellent job with prelaunch preparations over the last year, as noted on slide seven.
We’ve completed extensive payer research and payer ad boards and received positive feedback around our projected label, which is now very much aligned with the actual label that was provided by the CHMP.
A clear feedback from payers in all of our international markets is that they would support price parity to enzyme replacement therapy based on the value that they saw on our projected label and in our data which support the value of migalastat.
And behind the scenes, we’ve been working diligently on developing the Global Value Dossier and have begun to submit the dossier in certain countries where the reimbursement process is initiated upon positive CHMP opinion. We now expect to begin the country by country process in the remainder of the EU member states upon formal EC adoption.
So we feel very well prepared and pleased to have kicked off the country by country process and we’ve gotten great receptivity and we are very confident in the value proposition migalastat will bring.
As a reminder on slide eight, as John mentioned, the $1.2 billion global Fabry market today is large and continues to grow at a double-digit pace annually. We’ve prioritized the EU, Japan, US and other countries with large Fabry market for initial launch.
And importantly, of the 5,000 to 10,000 diagnosed patients around the world, we estimate that 40% to 50% of them are not currently on treatment and that there is further opportunity for growth and diagnosis through newborn screening and other initiatives such as screening in high-risk populations and general elevation of disease awareness.
We believe that the product profile for migalastat is an innovative new treatment – oral treatment option and will strongly position us for successful launch.
Turning to our global regulatory strategy on slide nine, it’s important to reiterate that the positive CHMP opinion and potential EC adoption provide a platform to address more than 70% of the global Fabry market, including the EU member states as well as several international territories that accept the European approval as the basis for authorization.
We won’t outline the full launch sequence for competitive reasons, but it will be similar to other products and rare diseases with a Germany launch first. And now, our entire German team is in place including the key account managers, our chems who are trained and ready to launch upon EC adoption.
As a reminder, Germany is currently the third largest Fabry market behind the US and Japan and has about 550 patients on enzyme replacement therapy today with a roughly equal number who are diagnosed, but untreated. So this is a great first country to launch migalastat in.
In rest of the EU, each country has its own reimbursement process which can take 6 to 12 to 18 months and we are pursuing each of them vigorously. In countries that offer specific pathways for innovative products with high unmet needs, we’re pursuing those channels where we can.
In the UK, for example, we've been selected to go through the HST process or Highly Specialized Technology process that was designed for orphan diseases with unmet needs where, among other things, the reimbursement will not be determined by quality or quality-adjusted life care.
And in parallel with the reimbursement process, we have initial patients being treated in France through our temporary authorization of use, or ATU. And the positive CHMP opinion allows us to now broaden our Expanded Access Program, or EAP, to additional countries that recognize the EU opinion.
This EAP program is important because it allows us to provide the earliest possible reimbursed access to migalastat for Fabry patients while we’re in the process of securing formal country-level pricing reimbursement and marketing authorizations.
And in the US, as John mentioned, we anticipate meeting with the FDA in the middle of the year and intend to provide an update on the US regulatory pathway after we receive formal minutes from that meeting. Finally, I would like to touch on one more important market, which is Japan, outlined on slide ten.
Japan represents another large Fabry market, in fact it’s the second largest Fabry market in the world, with an independent regulatory process that we are actively pursuing. Today, in Japan, there are more than 650 Fabry patients on enzyme replacement therapy, again, with a similar number who are diagnosed, but untreated.
And physicians tend to initiate treatment early in the course of the disease, so this is a very progressive and supportive Fabry community. To date, we’ve done a great job of laying the groundwork in Japan to deliver on our mission to make migalastat available as broadly and as quickly as possible.
We’ve fortunate to have had multiple sites in Japan as well as several Japanese patients who participated in our pivotal Phase III study, so we already have data in about half a dozen Japanese subjects with Fabry disease who’ve taken migalastat in addition to a Phase I PK study in healthy Japanese volunteers that was completed earlier in development.
Migalastat was also granted an orphan drug designation and we've already begun the process of interacting with the Pharmaceutical and Medical Devices Agency, or PMDA, on the optimal regulatory path forward. We hope to have an update on this process later in the year.
And finally, beyond the initial Fabry market opportunity, we would like to remind you on slide 11 that this is a significantly underdiagnosed and maybe one of the most prevalent human genetic disorders.
Through newborn screening initiatives, diagnosis is on the rise and these data suggest that Fabry may be up to ten times higher than historically reported in literature. A majority of patients identified through newborn screening have amenable mutations.
And as a reminder, when one patient is identified, typically three to five additional family members are also identified. I’m happy to address questions about launch preparations during the Q&A, but for now we’ll turn the call back to John's outline on Fabry franchise strategy..
Great. Thank you, Brad. So on the heels of a successful positive CHMP opinion, I’d like to reiterate our commitment at Amicus to delivering the highest quality therapies for all individuals living with Fabry disease.
We begin, of course, with migalastat as a personalized medicine for patients who have amenable mutations as identified in our proposed label. For all of the patients with Fabry who do not have an amenable mutation, there has been a lack of innovative new treatment option now for more than a decade.
We hope to change that with our development of a novel proprietary biologic, our own Fabry ERT. As we’ve outlined on slide 12, our target product profile is a Fabry ERT with improved drug targeting and we expect our CHART platform technology to further differentiate this product for co-formulation with migalastat.
This cell line has been identified based on the work done over the last several years by Dr. Do and his scientists here at Amicus. This cell line has now been transferred to our manufacturer and we expect to provide more information including pivotal preclinical data in the second half of the year.
As you can see on slide 13, it is our vision that patients with amenable mutations receive a personalized medicine with oral migalastat as a monotherapy, while patients with non-amenable mutations may receive one infusion, a novel ERT that incorporates the stabilizing properties of this chaperone and that in the future we have all Fabry patients on an Amicus product, driven entirely by the human genetics.
Beyond that, we continue to innovate as part of our commitment to the Fabry community to discover the future next-generation therapies. And in the months ahead, we’ll have more to say about our Amicus pledge to patients in Fabry disease.
Turning now to our Pompe program, you can see here on slide 15, building again on the biologic capabilities that we’ve developed here at Amicus, our manufacturing relationships with key contract manufacturing organization, we set out a number of years ago to address three primary challenges with enzyme replacement therapy, the current standard of care.
The first is activity and stability. What you see, of course, with the current standard of care, the approved ERT, is a rapid denaturation of ERT in the pH of the blood. You also see protein aggregation. Secondly, the challenge of tolerability and immunogenicity.
You see infusion-associated reactions in greater than 50% of late-onset Pompe patients and antibody titers have shown to affect treatment outcomes. It’s also been reported that all patients develop antibodies to the current standard of care.
The third challenge – and this is a challenge owing to the structure of the primary protein and its carbohydrate structure, and that’s the challenge of uptake and targeting. What you see with the current standard of care is very low mannose 6-phosphate receptor uptake into skeletal muscle.
In fact, the vast majority of that GAA or Pompe protein is not delivered to the target lysosomes of muscles. The challenge I’ve put out our science teams a number of years ago is to develop a novel ERT that would address all three of these major challenges.
To do that, our teams incorporated the CHART technology or Chaperone Advance Replacement Therapy, which is the addition of a chaperone to stabilize the ERT, enhance activity and stability, and potentially reduce tolerability and immunogenicity.
They also needed to invent an entirely new ERT that had a high level of mannose 6-phosphate and was properly glycosylated. We believe that we’ve now achieved that and are very, very pleased that that is now in patients. Let me briefly turnover on slide 16, the discussion to our Chief Science Officer, Dr.
Hung Do, who has also been a chief architect of this exciting new drug..
Great. Thank you, John. As John mentioned in the previous slide that the key component of our particular approach for Pompe disease is the development of an ERT that could be effectively targeted to key disease relevant issues.
And we have developed a robust, proprietary cell line which, in fact, does produce an enzyme, designated ATB200, that has optimized glycosylation for efficient drug targeting. We have worked diligently to scale up this process, so that we can develop this ERT at large-scale manufacturing.
So we actually have maintained these critical qualities of this protein during the scale-up of this enzyme, in particular maintaining high levels of mannose 6-phosphate to ensure good drug targeting. We have verified that glycosylation of our product has been maintained throughout this process, as can be seen on slide 16 on the left.
The graph represents the ability of our enzyme to bind the intended mannose 6-phosphate receptor to ensure good general uptake. As can be shown on the right-hand side, this is a vial of our drug product. To date, we have generated multiple GMP batches of our drug, which is supplied for our clinical studies that are being enrolled now.
With that, let me turn it back over to John to discuss our clinical study design..
Great. Thank you, Hung. And again, great that this is now in patients.
I will emphasize that what we've done is also not just – it’s not just differentiated in the current approved standard of care, we also think that is highly differentiated from any other ERT in development today, specifically in terms of addressing the three key limitations of the Pompe ERT.
The other point that I’ll highlight, we went through, and Hung showed, the chromatography slide of what we have done in not only designing this novel ERT, but in successfully scaling it through the manufacturing process and maintaining the high level of the mannose 6-phosphate and the entire carbohydrate structure, including the proper glycosylation is a remarkable achievement.
It’s something, to our knowledge, that no one has ever been able to do in the Pompe field before and we think really reflects well on our growing and unique capabilities in biologics design and now manufacturing.
On slide 17, we’ll see here, we are actively enrolling patients in our ongoing Phase I/II clinical study to investigate this proprietary Pompe ERT, ATB200, again co-administered in a fixed dose regimen with our chaperone AT2221.
As a reminder, this is an 18-week safety and PK study beginning with three ascending doses of ERT, the ATB200 alone, followed by that ERT plus chaperone. Following this 18-week treatment period, patients are eligible to continue to receive ERT plus chaperone.
Initially, the clinical study will look at patients switching from Lumizyme, the ERT standard of care. Key things we’re looking for in this study to differentiate our product candidate includes safety and plasma PK to demonstrate potential benefits of the addition of the chaperone to inform dose selection for our next study.
Also tolerability and infusion associated reactions will be observed as well as antibodies and the characterization, importantly, of the types of antibodies, some of which are now based on proprietary assays that we’ve developed here at Amicus. We expect to include patients naïve to ERT in the study after we have the initial switch data.
We will continue to follow these Pompe patients in an extension study where we will look at longer-term functional measures of the disease and assessment. So, again, over the last several months, a great achievement now with this drug in patients. I’m happy to answer questions on the clinical programs during the Q&A.
But, for now, let me turn the call over to Dipal Doshi, our Chief Business Officer and also General Manager of our Scioderm business unit focused on EB..
Thanks, John. I’m pleased, on slide 19, to provide an update on our EB program and the progress with our ongoing Phase III study, which we have named the ESSENCE study, in patients with all three major types of EB. In the third quarter of 2015, we acquired SD-101, a late stage potential first-to-market topical treatment for EB.
EB is a chronic, rare, genetic connective tissue disorder with no approved treatment option. While the blisters and lesions typical of EB are visible on the skin, it is not a skin disorder. It is a rare genetic disease that can affect all layers of the skin and internal organs. EB is a debilitating, excruciatingly painful and potentially fatal disease.
It is a disorder with 30,000 to 40,000 diagnosed patients in just the US, EU and Japan. We’re fully aligned with a sense of urgency among the EB community to get a treatment approved. And since the acquisition, we have made significant progress in adding our Amicus resources, experienced in clinical operations capabilities to this program.
Since the acquisition, we have applied our previous success in global clinical trial recruitment in rare diseases to increase the number of clinical sites in our Phase III ESSENCE study. And today, we have 16 sites with many more sites coming online in the coming weeks.
We believe it is important to have this wide geographic experience with SD-101 among several leading physicians and their patients. We are more than 50% enrolled today and expect momentum to begin picking up even more as these new sites come online.
We've also spent quite a bit of time building relationships and visibility within the dermatology community. We presented the Phase IIb data to the dermatology community, first at the American Academy of Dermatology and now at the upcoming Society of Investigative Dermatology.
We’ve also continued to strengthen our relationships with EB patient community and continue to believe we are well-positioned for success in our Phase III study. We remain on track to complete enrollment midyear and would continue to expect to report top line data in the second half of this year.
I will turn the call over to Chip to review our financial position..
Okay. Thanks, Dipal. Good morning, everyone. I’ll start today’s financial discussion with a few comments on our current cash position and our overall 2016 financial guidance. I’ll refer you first to slide 21. Amicus continues to maintain a strong balance sheet.
Cash, cash equivalents and marketable securities totaled $165.9 million at the end of March as compared to $214 million at the end of December last year.
During the month of April, we strengthened our cash balance with the addition of $16.2 million of net proceeds from the sale 2.1 million primary shares under our at-the-market or ATM financing facility. We also intend to access an additional $10 million of debt under an existing debt facility during the second quarter.
Based on the detailed financial review after the positive CHMP opinion and through the continued careful management of expenses, we expect to remain within the original 2016 net cash spend guidance of between $135 million and $155 million.
The current cash position, including proceeds raised from the ATM and the additional debt, is projected to fund our operations into mid-2017 through several important inflection points that John outlined previously in the call.
Turning to the first quarter results, I’ll be referring to slide 22 and additional details will be found in our Form 10-Q which will be filed later today. Total R&D expenses for the first quarter of 2016 increased to $23.4 million as compared to $16.1 million for the first quarter of 2015.
The increase is primarily due to higher contract manufacturing and clinical research investment, driven by the scale up of our Pompe ERT manufacturing efforts as well as investment of our Pompe and EB clinical development programs.
Total general and administrative expenses for the first quarter of 2016 was $15.7 million as compared to $6.4 million in the first quarter of 2015. The increase in G&A was primarily due to investment in pre-commercialization activities.
Net loss for the first quarter of 2016 was $43.7 million or $0.35 per share compared to net loss of $24.3 million or $0.25 per share in the first quarter of 2015. The wider loss is attributed to an increase in total operating expenses. And as of March 31, 2016, we had approximately 125.2 million shares outstanding.
This summarizes our key financials for the first quarter of 2016. As I said, more information on our financials will be available in the 10-Q which will be available later today. I’m happy to address any additional questions on financials during the Q&A. And for now, I’ll turn the call back to John..
Great. And thank you, Chip. So I will conclude on slide 23 by noting that it has been a remarkable start to the year for Amicus. And ours is a story of exceptional patient focus and perseverance. Amicus is about invention and healing the development and approval path for migalastat.
It was certainly not a straight line and we had to overcome many obstacles along the way. And such is almost always the case where drugs that represent highly innovative technologies and meaningful differences for patients.
The result of all that hard work is a CHMP opinion that validates the effort and the perseverance and what it could mean for Fabry patients. 2016 is poised to be our most significant year ever.
And much like CHMP opinion as it had validated migalastat as a meaningful therapy for Fabry patients, we expect to see Phase III data for the EB program that, if positive, will validate our purchase of Scioderm last year.
And very importantly, we expect to see Phase I/II data from our Pompe program which we hope will validate both the program and, more broadly, our capabilities as a biologics company. Any one of these programs could be the basis of a promising rare disease company.
So taken together, we think that these programs and the technologies behind them and our pipeline position Amicus in the coming years to become one of the leading global rare disease companies. So with that, operator, we’ll turn it back to you and we’re happy to take any questions..
[Operator Instructions]. Our first question comes from Ritu Baral of Cowen. Your line is open..
Good morning, folks. Thanks for taking the question. John and Brad, you mentioned that you intend to price migalastat at parity or at least you have updated [ph] for parity pricing to enzyme in Europe.
As you understand it now in your market research, what exactly is the price of enzyme in Europe after all the mysterious discounts the various countries get?.
Sure. Thanks, Ritu. I think you’ve articulated it well. That’s been our strategy and I think the data and the package that will be out very much support that strategy. So we’ve said, historically, that the global average price for an average patient's ranges around $250,000 to $300,000.
That included the US, by the way, where ERT prices tend to be higher over time. In Europe, that average price for an average patient from a gross perspective is about $250,000. And after gross to net, it’s different by different country, but you can assume that there’s something like a 20% discount off of that.
So perhaps $200,000 as a base point for a net price in Europe. But, again, it is different country by country. There are some countries that have a higher average starting point and some that have it lower. But that's probably a good rule of thumb at this point..
Got it. That’s very helpful. And then if I could circle back to your US strategy, John, I think you mentioned that you intend to go back to the FDA with the integrated database, a safety database, the GI data and the biopsy data, including – I think the prototype data is presented at WORLD.
What is the strategy of your argument as you go back into this meeting? What do you think, based on your interaction between receiving those very controversial minutes, now what do you think is going to be most meaningful to them in the data package right now?.
Ritu, I won’t comment specifically on our regulatory strategy. What I will remind everybody is that our last two sessions in the fall with FDA, they indicated that there were multiple potential approval pathways under either Subpart H or full approval. We think we have a very, very strong data set here. It’s only been strengthened since the fall.
We think the EU approval and the strength of that approval is further validation and support. We also think the potential with a publication of the 011 US study – talk to your medical journal – could also provide further validation. So, again, we’ve gathered all the data that we have.
We’ve just about finalized the briefing documents and we believe we’ll have that discussion or potentially a series of discussions in the months ahead..
Got it.
Very last question, the expanded access program in Europe and other geographies that you mentioned, what are some of the geographies that may kick that off near-term?.
So we’ve already mentioned the EU process which we did receive approval for cohort ATU. We announced that a few weeks back. The other countries that key off of either the CHMP opinion or the adoption by the EC are countries like Spain, Italy, Turkey is another one, Brazil is an important one, and each have different nuances.
In some cases, it’s fairly straightforward like that cohort ATU process in France and other cases. In Brazil, there’s a very specific traditional process that has to be followed.
So we’ll be – just as the reimbursement process, a country-by-country approach, but we’re in every geography where we can, trying to take advantage of that, so we can provide access as quickly as possible to patients through those programs..
Helpful. Thanks for taking all the questions..
Great. Thank you, Ritu..
Our next question comes from Anupam Rama of JPMorgan. Your line is open..
Hey, guys. Thanks so much for taking question. Maybe a quick one for Brad, just kind of looking at slide nine about your global regulatory strategy. Given some of the updates from your rare disease peers this quarter, how are you guys currently thinking about the LatAm situation and how does that impact your regulatory strategy in that region? Thanks..
So, Anupam, as I just mentioned in the question from Ritu, we are pursuing the in-patient programs in Brazil, in particular, which has a very specific judicial process that has to be followed in parallel with pursuing the regulatory process in that country.
We’re looking at – LatAm represents a large Fabry population, very much in need of new treatment alternatives and, therefore, we are looking at that geography very carefully. And we will, as we’ve done in Europe and elsewhere, we will judiciously target the largest unmet need first and continue to expand out from there.
So I would expect, in addition to our extended access programs, we will provide kind of regular updates as we go through that process over the next 6, 12, 18 months. But it’s a very important market and one that we think very much deserves an opportunity for access to migalastat..
Great. Thanks for taking our question. .
Thank you, Anupam..
Our next question comes from Joe Schwartz of Leerink Partners. Your line is open. .
Good morning. Thanks for taking my question.
I was wondering, first of all, on your Pompe program, can you give us any order of magnitude on the type of data that we’ll see before the end of the year in terms of numbers of patients and, potentially, duration? And then, I heard you mention safety, PK, tolerability, immunogenicity, will there be any clinical measures captured and reported? And then, what's the right way to think about the form that you’ll release that data?.
Hi, Joe. I think we’ll have more of an update as we get deeper into that study by mid-year. But, again, to remind you that the first cohort of patients, about a dozen patients, that will be 18 weeks of data in the primary treatment period, we also do expect to study naïve ERT patients and non-ambulatory ERT patients as well in later studies.
So I think what you expect to see in the second part of year are data on those dozen or so patients at the 18-week point. So once we have that or some cohort of that that we’ll be able to provide data on the, as you indicated, very importantly, the plasma PK, the tolerability, the antibodies and immunogenicity.
And again, while those are not traditional clinical endpoints, we think they very much go to the nature of the mechanism of action here and the drug and the potential for clinical benefit.
In the extension study of those patients beyond the 18-week treatment period, we’ll be capturing, compared to their baseline as they switched from Lumizyme, we’ll be comparing what they look like in some of the more traditional measures, the six-minute walk test, force vital capacity, and other more clinical measures of disease.
So I think this will be a growing body of data throughout the course of the next year with some important interim look by the end of the year..
Okay, great. Thanks. That’s super helpful. And then if I could just ask on Galafold, in Europe, who do you expect to be the first adopters in terms of your understanding of how this market segments out? What does the market look like to you in terms of the types of patients? It’s clearly large, as you point out, and growing.
But there's some patients that you’ve studied on ERT, those who’ve been on ERT, but have been naïve when you treated them, there's women, there’s men, there's more or less severe patients on a number of different organ manifestation.
So how do you see this very large market coming on to your drug over time?.
Yeah. Joe, this is Brad. Good question. We’ve, obviously, thought a lot about the Fabry market and patient segments, et cetera. One of the great things, you'll recall, is that, of course, we’ve studied the two major segments, both patients on therapy, so potential switch patients, but also patients naïve to therapy.
And so, those data sets are what really lay the foundation for what we think is a very strong label and what the CHMP had indicated would be a first-line therapy for Fabry.
So we have very much identified, I think, patients in both of those segments who would eagerly look to take migalastat, both patients on ERT who are dissatisfied or who are looking for a treatment alternative, an oral treatment alternative with a lower burden of treatment, or patients who are newly diagnosed and are looking for product with the characteristics that we have in the label.
So we think we have advantages in both of those segments. And as I mentioned in the call, you have a roughly equal – you have about roughly equal number of both patients on therapy, on ERT today, as well as patients who are diagnosed, but untreated.
Perhaps I’ll leave it there, but this is going to the very specific commercial plans for those segments. But we think there's a robust opportunity in both..
Okay, great. And then, I think on your last call, you said you were hoping to complete enrollment in the Zorblisa Phase III by mid-year. And I noticed today that you’re still just saying over 50% enrolled, but adding additional resources.
So can you give us any update/granularity there, so we can have the right expectations?.
Yeah. No, we still expect enrollment completion by mid-year and data by the end of this year, Joe. So what we will not do is provide such granularity here as we go step-by-step through the study, except to say now that it’s more than half enrolled. I think the next update will be when the study is fully enrolled..
Okay, great. Thanks for taking all my questions..
Sure..
Our next question comes from Roy Buchanan of Janney Montgomery. Your line is open..
Hi. Thanks for taking the question. I had a quick one on ATM. If I read between the press release, I guess, and the slides, it looks like maybe the 16.2 million was all used in the quarter.
Was there any used in April?.
Yeah. Roy, it’s Chip. That was 100% completed after the quarter, so that the ending cash balance of $165.9 million did not include any of the proceeds taken down in April from the ATM..
Okay. That’s helpful. And I have kind of a speculative one, I guess, on Zorblisa. Have you guys ever considered maybe, regardless of the Phase III outcome, potential of a combo with either the cellular or gene therapies that are being tried? Thanks..
I think those are all possibilities. We’re constantly looking at all the new technologies being developed. As you know, Zorblisa is, by far, the most advanced program in clinical study. It is the only program also for all subtypes of EB.
For other specific subtypes, there are some very exciting, very early stage programs and technologies and we’re very familiar with them. And I think, down the road, there could be a potential to study those in combination.
There could be great synergies with what seems to be the anti-inflammatory and healing aspects of Zorblisa, together with other drugs that might get to the more fundamental mechanism of action..
Okay, thank you..
Very welcome..
[Operator Instructions]. Our next question comes from Salveen Richter of Goldman Sachs. Your line is open..
Thanks for taking my question.
So just first, with regards to the Fabry disease, when you talk to patient – when you do patient outreach programs, or as you've talked to physicians, how much of a factor is brand loyalty going to play in terms of getting patients to switch from the existing ERTs over to your therapy? And curious about plans and timelines for the Japan market.
And then the third question, with regard to Zorblisa, with the complete target wound closure rates of 60% to 82%, can you help us kind of frame what we should be looking for in the Phase III study here? And then, how would physicians use this cream? Would they use it on wounds or as prophylaxis? And what's clinically meaningful in terms of the outcome here?.
Great. Salveen, thank you for all three of the questions. I’ll take the first one in terms of brand loyalty and Fabry. We've been actively involved for a decade now with this Fabry patient community. It is a community still with great needs, great unmet medical need and a very, very sophisticated community.
My assessment is that they have absolutely zero brand loyalty. Their loyalty is in finding the very best therapy with their physicians’ advice, given that it’s an X-linked disease with their family members.
And that’s where we hope that the strength of the data and having this as an alternative therapy available, beginning in Europe and then hopefully around the world and ultimately in the United States as well, that will drive switching from ERT, we think, in substantial numbers of patients.
And also too, in that diagnosed, but untreated population, that’s about equal to the treated population today, we think that this – for those patients who have [indiscernible] failed ERT and for those patients who have not elected to take on the great burden of an every-other-week infuse therapy that this might offer a potential alternative treatment that they might not otherwise have.
So we’re very, very optimistic about the ability to deliver this medicine very quickly to a number of patients living with Fabry.
To speak to that, just briefly, further, if you look at our 012 study, which was a switch study, these were 60 patients, all with amenable mutations in Fabry disease, who all were on enzyme replacement therapy, either with Fabrazyme or Replagal.
Throughout the course of 2012 when we enrolled that study, every one of those patients voluntarily elected to give up an approved therapy for a fatal genetic disease in the absence of any pivotal data that we had. And this was at dozens of sites globally.
The fact that they did that then and that they continued on that therapy, I think, bodes very well in terms of the potential uptake of migalastat and speaks specifically to their need for newer and potentially better therapies.
And I think also too, our significant physician interaction globally over the last several years, but intensely over the last several months, has told us that this will – the decision to put patients on migalastat will be driven by data and good medicine. And there, I think we’ll be very well positioned.
You second question was about Japan, let me turn that to Brad..
I think, in Japan, I think the best thing to do is to say that we will provide an update later in the year as we progress that process. We have initiated discussions with the PMDA, so that is underway. And as I mentioned, we have laid a great groundwork for those discussions in our development so far.
But why don’t we wait for more detail after we’ve had the subsequent discussion with the agency and we’ll come back. And your questions around Zorblisa and the treatment paradigm there, Dipal, I’ll let you handle that question..
Salveen, I believe the first question was around the percentages that we saw in the Phase IIb study and how that may correlate to the Phase III.
I think the best way to answer that is that we’ve learned a lot about how to design the Phase III study based upon the data from the Phase IIb and from the Phase IIa which was the basis of the breakthrough therapy destination, I think the best way to view that is that we are hopeful that the Phase III trial results reflect those learnings and that’s how we’ve designed that trial.
In terms of how physicians will use the SD-101 on the wounds or prophylactically, we believe that if the drug is approved that they will use the SD-101 product on the different types of EB and it’s a very broad basis of utilization, considering the fact that the trial design has taken into account the different major subtypes.
So we plan on doing much more market research as the year progresses on utilization, but we’re confident that if we see the trial results that we would like to see and the data shows what the data should show that utilization from the physicians will be across all the different major subtypes of EB..
Okay, thank you..
Salveen, I hope that answers your question..
Yes, thank you..
Great, thank you..
There are no further questions. At this time, I’d like to turn the call over to John Crowley, Chairman and CEO of Amicus Therapeutics, for any closing remarks..
Great. Thank you, operator, and thank you all to the analysts for the excellent questions. Have a great day. Thank you..
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone, have a great day..