Ladies and gentlemen, thank you for standing by, and welcome to the PTC Therapeutics Second Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in listen-only mode. I would now turn the conference to your host, Mr. Alex Kane, Head of Investor Relations at PTC. Sir, please go ahead.
Thank you. Good afternoon, thank you for joining us to discuss the PTC Therapeutics second quarter 2020 corporate updates and financial results. Joining me on today's call is our Chief Executive Officer, Stuart Peltz, our Chief Financial Officer, Emily Hill, our Chief Development Officer, Matthew Klein, and our Chief Business Officer, Eric Pauwels. Before we start, let me remind you that today's call will include forward-looking statements based on current expectations. Please take a moment to review the slide posted on our investor relations website in conjunction with the call, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements, as any and such risks can materially and adversely affect our business and results of operation.
For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report, Form 10-Q, and annual report, Form 10-K, filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We will disclose certain non-GAAP information during this call, information regarding our use of GAAP and non-GAAP financial measures, and a reconciliation of GAAP to non-GAAP is available in today's earnings release. With that, let me pass the call over to our CEO, Stuart Peltz. Stu?
Thanks, Alex. Looking back at the second quarter, I'm proud of the continued strong commercial performance in our Duchenne franchise, with nearly 20% growth year-over-year, excluding Brazil. EMFLAZA had an outstanding quarter, with greater than 30% year-over-year growth. As you'll hear throughout the remainder of the call, despite the challenging environment due to the global pandemic, PTC has continued to execute in our commercial business and advance key platforms and programs in our pipeline. One of these key platforms is our validated small molecule splicing platform. As many of you know, the most advanced splicing program is risdiplam for the treatment of spinal muscular atrophy, or SMA, with a PDUFA date on August 24th, which is rapidly approaching.
We believe that risdiplam, which would be the first and only oral treatment for SMA, has the potential to be the most competitive commercial product for this devastating rare disorder. Risdiplam validates our splicing platform and represents how innovation can generate substantial value for all our stakeholders. When we started the SMA splicing program over a decade ago, it was considered a moonshot. The dominant belief at the time was that while splicing is a great target in principle, it is a mechanism that occurs with most all RNAs and cannot be selectively modulated with small molecules. Because of our deep understanding and expertise in RNA biology, we knew that RNAs were actually the first enzyme that could form unique structures for catalytic function that could be targeted.
We also knew that if successful, targeting RNA would lead to a new platform to discover compounds that could lead to multiple new treatment options for patients living with rare disorders. It represents a new paradigm for drug discovery. Over the years, we've built the splicing technology that led to the discovery of risdiplam into a novel platform. As we highlighted recently in our splicing platform deep dive, PTC has unique expertise in RNA biology. We have constructed an RNA-centric compound library, proprietary screening tools, a proven process to optimize compounds to bring them to the clinic, and a fully integrated global commercial infrastructure to bring rare disorder therapies to patients. As you may have heard on our recent deep dive, this is a platform that has a number of additional targets moving forward. We anticipate three to five splicing development candidates over the next three- five years.
The next splicing compound to enter the clinic is PTC518, our development candidate for Huntington's disease, which is expected to be a first-in-human trial later this year. In addition to Huntington's disease, there are exciting new splicing programs emerging from our deep pipeline, including SCOUT and NETO. We're also making progress in other platforms and programs in the second quarter. We strengthened our pipeline with the acquisition of PTC923 for PKU. PTC923 expands our platform capability through the addition of a late-stage program for inborn errors of metabolism, where we believe it has the potential to be the best-in-class treatment for PKU patients. We also recently initiated a phase II/III trial for PTC299 for COVID-19. We recognize that PTC299 has a unique dual mechanism that is potentially effective against both stages of the viral infection.
We worked with leading academic collaborators and quickly confirmed PTC299's antiviral activity against SARS-CoV-2 in vitro, moving rapidly into the clinic for COVID-19. The clinical trial is being conducted in two stages. We expect stage one to be completed in the second half of 2020 and anticipate reporting top-line results for both stages in the first half of 2021. We have multiple sites in the U.S., Brazil, Spain, and Australia, with additional countries expected to initiate in the coming months. Ultimately, it's a combination of the mechanism, the pre-clinical data, the well-established safety profile, and the compound's oral bioavailability that gives us great confidence in PTC299's potential as a treatment for COVID-19. One of the reasons that we took PTC299 forward is because COVID-19 global pandemic requires our industry to work towards a solution.
In addition to its obvious effect on the health of our individuals, COVID-19 has impacted many industries, including our own. At PTC, we took early and aggressive steps to mitigate potential risks to our operations. Despite the challenges presented by COVID-19, we have been able to execute on certain key programs and lessen the impact on others. As I mentioned earlier, we expect to initiate a first-in-human phase I trial with PTC518 for Huntington's disease later this year. In our Bio-E platform, the two potential registrational trials for vatiquinone, formerly known as PTC-743, remain on track to initiate later this year. We're particularly excited about these upcoming trials as they provide us for near-term opportunities to address two rare disorders with a significant unmet medical need.
In addition, as we recently announced, we initiated a phase I study for PTC-857, a second compound from our Bio-E platform, ahead of schedule. Before I pass the call over to the team, I want to touch on recent developments with Translarna for nonsense mutation Duchenne muscular dystrophy, the first product we discovered, developed, and commercialized by PTC. Importantly, the EMA confirmed the risk-benefit profile of Translarna with the sixth annual renewal of the conditional approval, which is the basis of our sales outside the U.S. The CHMP recently recommended revision to the Translarna label, removing the statement, "Efficacy has not been demonstrated in non-ambulatory patients." This change enables healthcare professionals to use their clinical judgment to make treatment decisions for their patients on Translarna who have lost ambulation. It also supports our discussions with reimbursement authorities on continuing Translarna treatments for patients who become non-ambulatory.
We have pioneered therapy for Duchenne muscular dystrophy and remain highly committed to the community. I'll now turn the call over to Matt for key updates on our clinical programs. Matt?
Thanks, Stu. To start, I want to build on Stu's comments regarding our team's response to the COVID-19 pandemic. Despite the many challenges, we have worked hard to mitigate the impact on ongoing and planned studies. Let me begin with Study 045, the U.S. Translarna dystrophin study. In developing the protocol for this study, we carefully considered every element of the design to minimize variability that could confound study results. This included the decision to use a single site for the study at UCLA, the method of muscle biopsy collection, and the method of biopsy sample analysis. I want to highlight that the protocol specifies that sample analyses will not occur until the end of the study. PTC and study investigators will be blinded to the results until all analyses are complete.
At this time, final study muscle biopsies have not yet been collected from eight remaining boys in the Study 045. Given the evolving COVID-19 landscape in Los Angeles and in other affected regions where study patients reside, we are continuously monitoring the situation to determine when it will be possible to safely obtain the final biopsies. We are also exploring all potential options in order to have a data readout by year's end. Of course, we have ensured that all subjects remain on Translarna until they are able to complete the final study visit. Turning to our Bio-e platform, we remain on schedule to initiate potential registrational trials of vatiquinone in refractory mitochondrial epilepsy in the third quarter and in Friedreich ataxia in the fourth quarter.
As we detailed in our Bio-E platform deep dive, the phase II/III mitochondrial epilepsy trial will enroll approximately 60 children with the most common mitochondrial disease subtypes that have refractory seizures as a key component of their pathology. This trial will include a one-month run-in period to ensure eligible subjects have a minimum frequency of observed motor seizures, followed by a six-month parallel arm phase in which subjects will receive either vatiquinone or a placebo. We estimate that the refractory mitochondrial epilepsy market is approximately 11,000- 13,000 patients in the U.S., EU, Latin America, and Japan. The phase III Friedreich ataxia trial will be a 48-week, double-blind, placebo-controlled trial and will enroll patients from the U.S., EU, Australia, and Latin America, where we estimate the FA market size to be approximately 25,000 patients in aggregate.
We are working closely with site investigator teams and advocacy organizations to ensure that subjects for both of pacritinib potential registrational trials will be able to safely travel to and from study sites. In addition, we have adjusted certain elements of the study protocols to minimize any potential disruption that could occur in the event of a second COVID-19 wave. As Stu mentioned, we recently announced that the first patient has been dosed in the phase I trial for PTC-857, the second compound from our BioE platform. This study is progressing well and we look forward to having data from a single ascending dose and multiple ascending dose studies prior to the end of the year. Turning now to the splicing platform, our Huntington's disease program remains on track to initiate first-in-human studies this year.
These phase I studies will include both single and multiple ascending dose regimens in order to inform safety and pharmacokinetic parameters and inform dose selection to achieve target Huntingtin mRNA level reduction in the range of 40%-50%. As you may recall, this strategy of validating target engagement and splicing activity in first-in-human studies was a key component of risdiplam's development program. Moving on to our gene therapy platform, due to COVID-19 related delays, we now expect to receive the final CHMP opinion for our AADC deficiency MAA in the first quarter of 2021. Analytical testing by our contract lab, which is needed to respond to standard review process inquiries, has been delayed as contract lab personnel and resources have been diverted to support their COVID-19 related efforts.
Turning to the BLA submission for AADC deficiency, the key gating factor remains the study of the surgical use of the intended commercial cannula to deliver gene therapy product to young patients. These treatment procedures have been delayed by hospital cancellations of elective surgeries due to COVID-19. These procedures are now scheduled to occur in Q3. We still expect to be able to initiate the BLA submission for AADC deficiency to the FDA in the second half of 2020 in the absence of additional delays. Finally, I want to share that we have completed the integration of programs from the Censa acquisition. We are in the process of completing the necessary non-clinical studies of PTC-923 to support the long-term dosing plan for the phase III trial in PKU patients. Despite there being two marketed products, there remains a large unmet medical need globally for PKU patients.
We look forward to providing additional insights into PTC923 PKU program in a deep dive later this year. As you've heard, despite the impact of COVID-19 on certain clinical programs and regulatory timelines, we have been able to advance a number of key programs and, in some cases, accelerate timelines. I will now pass the call to Eric to provide an update on the commercial business.
Thanks, Matt. As Stu highlighted, the DMD franchise had strong growth this quarter with both EMFLAZA and Translarna generating significant revenue in Q2. Outside of Brazil, our DMD franchise had an outstanding quarter with revenue growth of nearly 20% year-over-year. Let me start with Translarna. In our sixth year post-launch, we are exceeding expectations in key markets, with the exception of Brazil, which is one of the countries most severely affected by COVID-19. Importantly, we continue to find new patients in Europe, Latin America, and other key markets despite the challenges of COVID-19. Additionally, as Stu noted, we believe that the revision of the language on the Translarna label will be a positive for patients. We see the update as an opportunity to further educate physicians, caregivers, and patients on the impressive real-world results from the STRIDE registry and SYNERGY-DMD natural history study highlighting Translarna's long-term efficacy.
Let me provide an update on the group purchase order for Translarna in Brazil. As a reminder, in Brazil, the government is a central payer, by which only a few large group purchase orders are placed annually for the number of patients approved through the judicialization process. Due to the impact of COVID-19, there was an administrative delay with payers for this centralized order. We remain highly engaged with the Ministry of Health and are working to ensure that Translarna patients will continue to receive this important treatment. In addition to our ongoing meetings with the Brazilian government, DMD advocacy groups and KOLs are also making their voices heard to advocate for Translarna access in Brazil. These stakeholders are critical to ensure that payers have the most recent information on new and existing patients. Notably, we have seen a substantial increase in newly diagnosed patients in the second quarter.
We anticipate an order later this year for both existing and new patients. Now turning to EMFLAZA. We are hitting our stride in the U.S. by bringing awareness to the community on the critical importance of EMFLAZA treatment for all DMD patients. We continue to see ongoing improvements and greater efficiency supporting the business, resulting in more than a 30% year-over-year increase in second quarter sales. Based on early observations, we anticipate this strong performance will continue into the second half of the year. Our U.S. commercial team, comprised of regional account, patient engagement, case, and market access managers, identified new patients at a high rate this quarter and has helped accelerate time to commercial therapy. Patients previously on bridge therapy and patient assistance programs transitioned to commercial therapy even more rapidly in the second quarter. These new EMFLAZA patients included both naive and former prednisone patients.
Among our existing base of patients, compliance and adherence remains very high, and discontinuation rates remain low on EMFLAZA. Turning to Tegsedi. Launch activities in Latin America continue to progress well, and we continue to find new patients in Q2. We remain engaged in pricing discussions in Brazil and expect the process to be completed by the end of the year. In Brazil, during the second quarter, we filed with ANVISA for approval for Waylivra. Patient finding and early access programs for Waylivra are ongoing, and we continue to anticipate revenue from this product in 2020. To echo both Stu and Matt's comments, while COVID-19 has impacted certain aspects of the commercial business, we continue to drive key areas of the business forward. I will now hand the call over to our Chief Financial Officer, Emily Hill, to review our financial progress.
Thanks, Eric. I'm proud that PTC is in an excellent position to invest in our growing business and accelerate growth while maintaining fiscal discipline and a strong balance sheet. We recently completed the transaction with Royalty Pharma that brought forward $650 million in non-dilutive capital. As a reminder, we retain nearly 60% of the risdiplam royalty stream up until a $1.3 billion threshold is reached. After the threshold is reached, PTC retains the entirety of the risdiplam royalty stream. This deal structure allows us to benefit from risdiplam's meaningful sales potential. We believe risdiplam has the potential to be the most competitive commercial product in the SMA market and believe that its market potential exceeds current analyst consensus. We also retain all economics associated with the approximately $400 million in remaining risdiplam milestone payments from Roche.
As a reminder, we expect a $15 million milestone payment imminently associated with the filing of the MAA with the EMA. Following the first commercial sale in the U.S., we would receive an additional $20 million milestone payment. I now want to take a few minutes to highlight the second quarter 2020 financial results, which are summarized in the press release issued earlier today. Starting with our top-line results, we reported $75.2 million in total revenues in the second quarter of 2020, compared to total revenues of $85.5 million for the second quarter of 2019. As Eric mentioned, EMFLAZA had an outstanding quarter, and Translarna saw continued growth, with the exception of a delay in the group purchase order in Brazil. Translarna net product revenues were $38.6 million for the quarter. This compares to $57.8 million for the second quarter of 2019.
As I've said, sales for the quarter were impacted by a delay of the Brazil group purchase order, which accounts for the year-over-year decrease in second quarter revenue. For Emflaza, we reported net product revenues of $36.2 million for the second quarter of 2020, compared to $27.6 reported for the second quarter of 2019. Growth in net product sales were driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business. Non-GAAP R&D expenses were $168 million for the second quarter of 2020, excluding $8.6 million in non-cash stock-based compensation expense, compared to $54.5 million for the second quarter of 2019, excluding $5.5 million in non-cash stock-based compensation expense. The increase in R&D expense includes one-time charges associated with a recent acquisition and a manufacturing agreement.
Specifically, it includes $53.6 million related to the acquisition of Censa Pharmaceuticals and $41.2 million related to the MassBio commercial manufacturing agreement for our lead gene therapy program in AADC deficiency. The majority of these one-time expenses are non-cash charges for the current fiscal year. Non-GAAP SG&A expenses were $45.3 million for the second quarter of 2020, excluding $8.3 million in non-cash stock-based compensation expense, compared to $43.8 million for the second quarter of 2019, excluding $5.4 million in non-cash stock-based compensation expense. The relatively flat year-over-year change in SG&A expense reflects our ability to leverage our existing global infrastructure. Net loss was $181.4 million for the second quarter of 2020, compared to net loss of $41.8 million for the second quarter of 2019.
Cash, cash equivalents, and marketable securities totaled $498.9 million as of June 30th, 2020, compared to $686.6 million as of December 31st, 2019. Including the $650 million in cash received in July upon the closing of the deal with Royalty Pharma, unaudited pro forma cash equivalents, and marketable securities as of the second quarter would be greater than $1.1 billion. I will now hand the call over to the operator to start our question and answer session. Operator?
Thank you. Ladies and gentlemen, if you'd like to ask a question, please press star then one on your touch-tone telephone. Again, if you'd like to ask a question, please press star then one. One moment please. Our first question comes from Robyn Karnauskas of Truist Securities. Your line is open.
Hi, everyone. Thanks for taking my question. I'm going to ask a question that I get all the time upfront. Can you clarify for us, given the last deal you did, how important is business development for you versus, say, the development of your splicing platform, which I think a lot of people are really excited about? Help us understand how you prioritize your businesses. I think that's the most common question I get, so I'm going to ask it on the call.
Sure. Thanks for the call. Obviously, our overarching goal is always to bring innovative therapies to patients with high medical need. I think as you can see, we've built the company over the last 22 years and continue to build it to have a strong pipeline over the next 20 years. The strategy has really been to use the internal discovery capabilities that we've built, as well as business opportunities that continue to grow. The splicing platform, as you see, I think, has created a substantial value and risk to plan. I think from the deep dive, you could see the opportunities that are there and available. We plan as part of what we've done is to expand into that.
The way I look at this is really in a sense shots on goal, and that you need a relatively broad pipeline in order to bring a number of products. It'd be critical for growth. That's also true for business development, right? You never know for sure when things are going to be ready for getting to commercialization. We look to fill the pipeline as needed through business development. It's helped us to evolve and develop additional new core expertise, such as gene therapy, the redox, the inborn errors, and metabolism. These are important to us as well, and we think there's some near-term value creators, like in the inborn errors and metabolism. We'll be starting the registration studies. The Bio-e programs will be starting the two platforms that are also pivotal studies that are starting now, that could be in the 2023 timeframe.
There's a lot of value that we think we can do in terms of creating value. The way we're looking at that is we're highly excited about our innovation capabilities, and we're going to be pursuing them with great zest moving forward. We look for business development opportunities very strategically and in this case, now that we've built our pipeline and platform to vertically strengthen if we see something that's interesting. Then the other point is obviously the current platform is important. The therapeutic areas, the platform, and the commercial footprint, I think, is how we're going to continue to grow both the innovation but also the revenues for the company. Does that help you?
Yeah. I think the big question is focusing on business development in any way a distraction from developing your current drugs, in particular that splicing platform, which is a near-term catalyst?
Yeah.
That's a more direct question.
Yeah, I think that's fair. The answer is no, it doesn't. Our pipeline is not yet big enough to say that we're prioritizing A versus B, and that we have the resources to be quite focused to make sure, especially now, to really go whole hog through the splicing platform. I don't think it's a diversion, because there are obviously different people that are moving forward on this. The way we've actually constructed the team now or the company in terms of its organizational structure, isn't sort of pulling from one group to another. It's building out teams to be able to handle that and then have the infrastructure for them to be autonomous enough, but with enough oversight. I think we're pretty focused on that. We're strengthening our current platform. That's a very important point.
It's not like we're deprioritizing one for the other right now. We're not big enough yet to be able to say that we're going to be doing that. It's not a distraction.
Thank you so much. Got it. Thank you so much.
Thank you. Our next question comes from Joel Beatty of Citi. Your line is open.
Hi, thanks for taking the question. The first one is to follow up on that last question from Robyn. From a business development standpoint, what types of programs, what would you be looking for that would have the best fit with PTC, at least from a high level?
I guess from a high level. Oh, thanks, Joel, for that. When we tend to think of it from a high level, it's really to look at within the vertical. If you think about it, we now have either gene therapy, Bio-e, the splicing platform. It's within the platforms that we've built that we'll be moving. We're not looking to trade additional or in both areas of metabolism. We're not looking to go outside of that area. We're looking carefully for selective and strategic BD opportunities that focus efforts on the current therapeutic areas and platforms that we have in play. That can also help enhance our commercial footprint.
Okay. Got it. That's helpful. A question on risdiplam. Have there been discussions with FDA on the potential indication? Anything you can give that gives confidence on FDA meeting their PDUFA date? How do you anticipate the label could compare with the approved SMA drug?
Obviously, we're waiting for the PDUFA date. We strongly believe that it's certainly going to be approved by that time. We strongly believe it's the best-in-class product, and we think it's the most commercially competitive product out there. We think that obviously, from our point of view, it's going to have broad efficacy, will be the standard of care. We expect that the label is going to be very broad for all SMA types, including one, two, and three. Obviously, we have the data for placebo-controlled trials, both for SMA Type 1 for those younger baby patients. I think even there, when you compare the data sets in terms of even in the Type 1, the older patients have seen benefit there that wasn't seen by others. We think it's really quite strong.
With Type 2 and 3 in the older patients, we saw in the SUNFISH even strong data as well. It's also supported by the other programs, the JEWELFISH and RAINBOWFISH. At the end of the day, we think it's going to be a very strong label, for both the Type 1s as well as adolescents and adults. It's obviously the first and only treatment that's an orally bioavailable product, so it's home administration. In particular, in this environment now, that's a huge benefit. You don't have to go to the hospital to see a physician. There's a strong safety profile. We think that it's done quite well. We're very excited about that.
Great. Thank you.
Thank you. Our next question comes from Alethia Young of Cantor. Your line is open.
Hi, this is Li on for Alethia. Thanks for taking our call. Maybe just one on AADC. Can you just give us more color on the remaining steps to file BLA, how confident that you can file by year-end? Another one on the U.S. dystrophin study. Just wondering if you think the COVID challenges might make it harder to integrate the results given the delay. Is there any specific FDA guidance on it? Thanks.
Sure. Let me remind you that we'll talk about the BLA, but the MAA has been submitted. We're moving through Europe. The key gating item, as you know, is the surgeries with the commercial cannula. I'll let Matt. You want to talk a little bit about that, Matt?
Yeah, absolutely. As Stu said, the key gating item is the surgical procedures with the intended commercial cannula, which is a SmartFlow cannula. This is CE marked for gene therapy delivery in the EU. In the U.S., it's an approved device, just not explicitly for the delivery of gene therapy into the subthalamus. It has been used in clinical trials with a good safety record for gene therapy delivery into the subthalamus of adults. Really that last piece is getting some experience in the surgical administration of the gene therapy product with the SmartFlow device. It's really an assessment that we've been asked to provide of the device and the surgical procedure for the delivery of gene therapy product into subthalamus.
Once we have those procedures completed, we will of course move forward for final BLA discussions with the agency, then move forward with preparation for the submission. With regards to the dystrophin study, obviously, we are all frustrated by the delays from the COVID-19 trial. I mean, PTC, as you know, has an incredible, long-standing history of being dedicated to developing therapies, specifically Translarna DMD patients. We are obviously incredibly excited to receive the six-month renewal in Europe. The evidence that we are continuing to collect on a number of fronts show long-term benefit through our STRIDE registry. Now we are at the point that we are just waiting for these last eight patients to come in and get their final biopsies so we can analyze all the results. I mean, clearly, we want to get this study read out by year's end.
There's some unpredictability due to the pandemic, which is obviously affecting not only the study site in California, but also in the states where some of the patients live, such as Texas and Arizona. Of course, first and foremost, we want to ensure the safety of the procedures. We're still in the process of sorting out the exact timing of biopsies at UCLA. Fortunately, it looks like pandemic numbers may be slowing, we're in constant communication with the site to see when we can get a better idea of the specific timing for those final biopsies. Of course, most importantly, we're ensuring that these patients don't have any disruption in the supply of Translarna, that when we're able to get their biopsies, we'll be able to do so in the context of ongoing Translarna treatment.
Thank you. Our next question comes from Joseph Thome of Cowen and Company. Your line is open.
Hi there. Thank you for taking my questions. The first one on the MAA for AADC. I think you indicated that the EMA had some feedback on some additional information that they need from you. If you could just qualify what sort of information do they need, and did they put you on a stop clock so you have that extra time to respond, or is there a time limit? Second, if you could just update us on the progress for INDs for PTC, for Friedreich ataxia and Angelman syndrome.
Sure. Matt, do you want to talk a little about the MAA?
Yeah, absolutely. Thank you for the question. As we mentioned, we submitted the MAA in January, and based on the standard MAA timelines, we expected the final CHMP opinion in late December of this year. That's just based on the pre-specified timeline from the EMA. During the review process, the agency asked us some pretty standard questions wanting additional manufacturer-related analyses done on the drug product. These were all done by our external commercial manufacturing organizations. They have been impacted by COVID in a few ways. One is obviously decrease in the number of available personnel, but also our lead CMOs are involved with other companies in developing solutions for the COVID pandemic. Obviously they've redirected their personnel and other resources towards the COVID-related activities.
In order to be able to satisfactorily respond to the EMA's questions to us, we were granted a stop clock so that we can then obviously come back and address the questions, which are easily addressable once we have the available resources to do so and plan now on the final opinion in Q1 of 2021.
Great. Thank you. Just the update on when we could see the IND for Friedreich ataxia prevention therapy, if there's any update.
I think we said it was delayed. We announced last quarter that we're continuing to work to advance them both. There's been a number of COVID-related delays for at least a quarter. We really do remain enthusiastic about both of these programs. We're working to really get it all done so we can get that done. That's where we're at now. It's similar to what we reported the last time.
Great. Thanks again.
Thank you. Our next question comes from Brian Abrahams of RBC. Your line is open.
Hi, this is David Suciu on for Brian. Thanks for taking my question.
Sorry, what was that?
Hello?
I think your line is not muted, ma'am. Okay, go ahead, David. Sorry.
No worries. Just another one on AADC. From your ongoing pre-launch activities, maybe engaging in the gene market, can you just update us on your evolving sense of the clinical pathway to identify AADC patients and if there are perhaps differences in the U.S. versus EU? I'm just trying to get a sense of what your current level of confidence is in that be here. I have a follow-up after this.
Sure. Eric, you want to talk a little bit about our patient finding efforts?
Yeah, sure. I think we are continuing to work very hard to identify AADC patients. Despite COVID-19, we've actually been raising disease awareness and driving testing, particularly in patients that are in high risk. Through neurology clinics and epilepsy clinics. We've accelerated a lot of our master class symposiums with agency opinion leaders programs, ad boards, steering committees, symposiums. We've actually published clinical data. In terms of raising disease awareness, we've really increased our level of activities for awareness and identification. We've also expanded a lot of our activities to a number of different countries as well, both in Europe, Asia Pacific, and Latin America. In addition to that, we've been having a lot of payer discussions, and they really do like to see the clinical data to understand the gene therapy landscape and to look at the value proposition.
Patient identification continues to progress well. As we said, our goal is to find 300 patients by the time we're prepared to launch in our first few markets globally.
Thank you. Maybe just a quick follow-up on Translarna again. Going back to your opening remarks discussing the recent CHMP recommendation to open the label to patients who become non-ambulatory. I was just wondering if you could provide maybe an update to you on any other evolving dynamics among physicians in the EU, and if you have any perspective on expanding Translarna's label to initiation among non-ambulatory patients.
Yeah. Thanks for that question. We were really heartened by this and had substantial positive feedback from both physicians of payers on their revision. This really does allow the patients to have a path to remain upon Translarna even as they transition to the non-ambulatory part. That's actually really important. Certain countries had already had the willingness to do this. In terms of non-ambulatory, that really is sort of country by country as well right now. Certainly, when you think about it makes sense from this point of view that if you're non-ambulatory, from going from ambulatory to non-ambulatory, that you'd like to. We have been working on that. Maybe a little bit, do you want to talk a little bit about this, Eric, in terms of what Europe is doing.
Yeah. First of all, we've had a lot of feedback immediately after the announcement. Physicians and payers have looked at this as being a positive step forward. Immediately after that announcement, a number of patients that might have been actually considered to stop because they were non-ambulatory continued treatment. This willingness, if you will, to not implement a stopping criteria was critically important. Since we've already actually seen patients that have been on Translarna go non-ambulatory and stay, it gives a lot of the physicians positive feedback and continue, if you will, this dialogue that they could have right now, they couldn't with certain payers in Northern Europe, in Southern Europe, and even in places like Latin America, where payers use the wording of the label as a sort of stopping barrier or stopping criteria.
There's going to be now and in the future, I think patients and physicians will have a positive benefit discussion with payers. By removing that in the label provides, if you will, a constructive dialogue that can be handled by the physician and the payer.
Yeah. The other piece is we've done a fair amount of work both in our STRIDE registry as well as the non-ambulatory patients following them. What's really nice is that the results that we saw in the clinical data have been shown with patients, and actually you can use now much harder endpoints. The publications on the trial data is really quite clear in terms of the substantial improvement on not only the walking longer, but multiple other time function test measurements where you see substantial improvement. What we've seen is in the non-ambulatory patients, clearly better pulmonary function. I mean, very clear demonstration when compared to natural history. We're excited about this and we do try and work to make sure that non-ambulatory patients have a way to get Translarna as well.
Great. Thank you.
Thank you. Our next question comes from Raju Prasad of William Blair. Your line is open.
Hi there. This is Sami on for Raju. I had a question regarding the dystrophin study. At what point or what would be the scenario in which you forego the biopsies or a portion of them in order to file that BLA? I'm trying to understand which event you're prioritizing.
We have 12 out of the 20 that have been done and that have been treated, and they're still blinded, so we don't know the data within there. The study was performed with 20 patients pre- and post-, and they're still being treated. We just think that it's better to have all the patients if possible. If this continues and extends on, there is a possibility we could say maybe we should just look at the data now in an interim way and take a look at that. We'd obviously need to align with the FDA on that before we were to do that. We don't want to look at the data before we agree with that. It's really a question of if we think it's going to take forever or not. That's our thought on that.
Okay. That was really helpful. Just a quick follow-up. How are patient identification efforts for the mitochondrial epilepsy trial, just to get an idea how quickly you will be able to enroll patients in that trial?
Sure. Matt, you want to sort of talk a little bit about patient identification for the trial?
Yeah, absolutely. Just for some historical background, PTC743 was really the first drug to be brought into the clinic explicitly for pediatric mitochondrial disease patients and has an enormous amount of brand recognition in the mitochondrial communities globally. We also have very good working relationships with the patient foundations both in the U.S., EU, Australia, Japan, and so we've been relying on this network to help us get the word out that this trial is starting. There's already a great deal of enthusiasm in a number of the countries in which the trial is going to be conducted. We are really excited to be able to launch the trial and believe that we can rapidly enroll the trial, again, COVID permitting.
Great. Thanks for taking my question.
Thank you. Our next question comes from Gena Wang of Barclays. You want to go ahead?
Hi. Thanks for taking our question. This is Peter for Gena Wang. I guess two questions from me. First, on Translarna. How much of the quarter-over-quarter decline is due to COVID-19, and any color on impact on new and existing patients? For back half of the year, do you expect some growth relative to the first two quarters or largely stable excluding the Brazil order? I have a quick follow-up. Thank you.
Okay. Say the first part again.
For Translarna, how much of the quarter-over-quarter decline is due to this pandemic?
Oh, okay. Great. Yeah. Eric, you want to talk a little bit about that?
Yeah, sure. I think there's very little decline if we look at the major markets. In fact, I think Translarna in all key markets outside of Brazil has continued to grow, and we've continued seeing new patient identification, and new patients come onto therapy even in some of the most affected countries like in Southern Europe, like Spain and Italy, where we've had new patients go onto treatment. We've also seen very high adherence rates, compliance rates, and very low drop-outs. Essentially, in the main areas, in the main regions, we haven't actually seen that much impact at all from COVID-19. The main issue in decline is primarily the administrative delay from Brazil in the group purchase order at this time.
Yeah. I think also you might remember, Peter, in my comments initially, I said outside of Brazil, we saw approximately a 20% increase.
Right. Okay. Thanks. Thank you. I guess my second question is, to the extent that you can provide any color on risdiplam EAP, would you be able to give color on how the enrollment rate has been impacted by COVID-19 relative to your expectations and any color on folks switching from ZOLGENSMA? Thank you.
Yeah, sure. I guess, I don't think we've ever given numbers on how things are going. Things actually, in terms of EAP, have gone actually quite well. I know that Roche is quite satisfied with how the EAP has been going. We do expect on approval that we think that obviously we're confident of Roche's ability to launch this quickly, and we think in particular, there'll be a lot of transition from SPINRAZA to risdiplam. We think that's going to be a very strong part of the growth of risdiplam over time, as well as obviously the naive, in particular the adolescents. There's so many patients that are not being treated that I think risdiplam as an orally bioavailable agent is very well suited for these patients. We're excited about this launch, which we anticipate will occur quite quickly.
Thank you. Our next question comes from Eric Joseph of JP Morgan. A lot of okay.
Yeah, thanks for taking the question. Just on Translarna, picking up on your prior comments about discussions with EMA and health authorities. Can you talk a little about the extent to which they are interested in results from Study 45 as they look to potentially renew conditional approval again in 2021? I think it's from health authorities view, I guess, is there any sensitivity on their end on Study 45 outcomes versus how to look at the STRIDE registry data?
Oh, yeah. Sure. Thanks for that, Eric. I think one important point there is that it was very clear that the European authorities didn't look at dystrophin as a biomarker that reasonably predicts any efficacy. Really, everything was based on the clinical results. We've kept them apprised not only of the clinical data that we have, but also the clinical data from the STRIDE and the non-ambulatory data. They know that data quite well. The results from Study 45, I don't think will be of any service in the EMA sense, whether good or bad, because I don't think that it isn't a biomarker that I'd go reasonably predict clinical benefit. They had no interest in it in the past. I think you could see from another company when they talked about their results that they didn't make any headway either.
They're not using this as something that's an approvable biomarker. That's, I think, true with most other countries outside of the United States.
Got it. That's helpful. Maybe a follow-up on Inclasa. Just wondering if you could help us unpack the dynamic to the strong quarter here. How much is sort of driven by efficiencies in the prior auth process versus growth in new patient adds among naive patients? We should be able to anticipate a similar benefit in the second half of the year. I guess also, we also just noticed that the phase III limb-girdle study also completed enrollment recently. Can you just remind us whether this is a potentially label expanding trial and what regulators might be looking for to enable that. Thanks.
Sure. In terms of the Emflaza, obviously we've been spending the last couple of years in terms of gathering data, and the publications, I just think are so clear in terms of demonstrating why Emflaza is the superior. The data just shows that it's a superior product relative to prednisone, and I think that there's been a lot of hard work done on that to get to this point. I think this growth. Maybe, Eric, do you want to talk a little bit about the growth of Emflaza in terms of patients and such?
Yeah, sure, Eric. Good question. We're really pleased with the growth right now that we've seen from EMFLAZA. The majority of the growth right now is that we've been able to convert patients that have been on bridge and have patient assistance. We've been able to convert them much, much faster to commercial therapy, which is extremely important because that's free drug. In addition to that, we have continually increased the number of new prescription start forms during the quarter, and we saw a nice increase there and an influx of both, a nice combination of naive and former prednisone. The other thing that's driving it is that the base of patients are, again, like Translarna, we're seeing very high adherence and very good compliance rates and very low dropouts.
We've also come into a period of reauthorizations, and our team is staying way ahead of the reauthorization process and with the insurance companies, so that patients can spend less time in that bridge environment of free drug and more on commercial therapy. It's a combination of a lot of these different efficiencies that have really driven this growth. We're seeing that again. It's looking real strong as we're moving into the second half of the year.
Yeah. Got it. On limb-girdle too?
Oh, the limb-girdle. Yes. My recollection, I can't remember whether that was on the call or the Q&A or not.
Yep
I do think it was. That's one where I don't think we actually completed the enrollment.
Yeah.
I think it's been, especially with COVID, it's been substantial recruiting challenges.
Understood. Thanks for the clarification there. Thanks for taking the questions, guys. Appreciate it.
Thank you. Our next question comes from Martin Auster of Credit Suisse. Your line is open.
Hi, this is Matt Toro, on for Marty. Thanks for taking my question. Regarding the Huntington's program, you mentioned that phase I healthy volunteer data will include information on Huntingtin lowering in plasma, and I believe you presented some data on mice on the relationship between Huntingtin lowering in plasma versus the brain. Does your therapy lower Huntingtin protein in non-human primates? If so, can you describe the relationship you saw in NHP in terms of Huntingtin lowering in plasma relative to various regions of the brain? Thanks a lot.
Sure. Yeah. You're absolutely right. To remind everyone, it's the Huntington's program, which you might have seen on the deep dive, was that you take what we call the pseudoexon, and be able to trick it into being able to go be part of a messenger RNA, which actually makes the RNA unstable because of a premature stop, and you don't make either the protein or the RNA. That's really actually quite important, and that's the human form of it. My recollection is that the non-human primate, because it's within the intron, doesn't have that sequence in it, so you wouldn't necessarily see that. That's my recollection of that. It's not in the sense a model, where you could do the substrate, where you can actually look at the substrate, the human substrate in that case.
Great. Thanks so much for the question.
Right. It is very true that in the patients, we'll very much be able to measure in blood the reduction of the RNA and potentially protein, especially in the multiple ascending dose, whether you have time to see the protein go down. We do know from measurements that the blood-brain levels are pretty much 50/50. What you see in blood, we anticipate will be similar to what we see in brain, and that was indeed the case in the animal model. It's really quite exciting. It's actually very similar to, analogous to what we saw in the SMA program or what we anticipate to see. You have really an idea from the very early stages of the program that you're on mechanism, on target, you see the effects, and then you go on to measure clinical benefit.
Perfect. Thanks again.
Thank you. I'm showing no further questions at this time. I will just turn the call back over to management for any closing remarks.
Oh, okay. Well, thank you folks for staying on the call and asking these questions. We're obviously very pleased with the strong performance of this quarter across both the commercial and clinical programs, and I'm very proud on how the teams have continued to execute in the environment that we're in. As you know, we've been trying to do our part to reduce the consequences of the pandemic. You saw that, and that we're very excited about PTC299 and its potential to be part of the solution for COVID-19. We've also, as I talked about before, recently launched our internship program for providing opportunities for graduates, which we call the Talent Pipeline Program or TPP. It offers a one-year internship to provide real-world experience for graduates during the challenging economic times.
Although all graduates are eligible, we've used this program to reach out to institutions, minority communities, and I'm gratified to say we approximately have about 3,000 applications. It's been quite successful. We're excited to be able to work alongside and mentor what we hope will be future leaders in the biopharmaceutical community. Thanks again for listening, and we hope that everyone stays safe.
Ladies and gentlemen, this does conclude today's conference. Thank you for participating, and you may all disconnect. Have a great day.