Ladies and gentlemen, thank you for standing by and welcome to the PTC Therapeutics First Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participant lines are in a listen-only mode. After the speaker's presentation, there will be a question- and- answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Alex Kane, Head of Investor Relations at PTC Therapeutics. Thank you. Please go ahead, sir.
Good afternoon. Thank you for joining us to discuss the PTC Therapeutics First Quarter 2020 Corporate Updates and Financial Results. I hope that everyone is doing well and staying safe. Joining me on today's call is our Chief Executive Officer, Stuart Peltz, our Chief Financial Officer, Emily Hill, as well as Matt Klein and Eric Pauwels, who are recently appointed Chief Development Officer and Chief Business Officer, respectively. 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 risk 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.
Thanks, Alex, and thank you for joining us today as we provide an update on the first quarter. I hope that everybody is staying safe and healthy amid these challenging times. I'm incredibly proud of how the PTC team has responded to the COVID-19 crisis, recognizing the seriousness of COVID-19 and acting early. In late February, we understood the threat and set up a COVID-19 task force that included individuals from all areas of expertise of PTC, including physicians, public health experts, and epidemiologists that understood the implications of the viral pandemic. This team immediately implemented a plan to safeguard the health and safety of our employees and ensure that they had the necessary equipment to work effectively from home. This task force continues to meet and refine processes that allow us to remain productive and safe.
We have a second task force that focuses on critical aspects of our business to ensure access to our therapies. This task force is continually assessing issues that could arise with our clinical programs, manufacturing, supply chain, research, as well as the commercial business. We have devised strategies to mitigate potential issues in our businesses and are continuously assessing how well they are functioning. Patient services and engagement teams are now working together to ensure that patients have the necessary access to treatment. We have also created a third COVID-19 task force, whose mission is to look at what is next and think through the strategies we should employ as the world begins to open from being locked down. Their job is to strategize multiple scenarios of what will be needed to be successful in different places around the globe.
As a result of these efforts, our teams have adapted and have continued to execute. Field teams are engaging with the physicians, identifying patients, and driving awareness of our commercial products. Given the limited ability for personal interaction, they are doing so remotely using a number of digital approaches. Our scientists have also continued to work in the laboratory to drive critical research programs forward. We have put safeguards in place, including staggered shifts to allow reduced interaction so that they can work in a safe environment. As all companies in the industry have experienced, ongoing and planned clinical trials have been impacted as hospitals and healthcare providers focus on treating COVID-19 patients and have slowed or closed sites. The effects of COVID have also impacted regulatory filings in our gene therapy programs. Matt will talk more about these programs. Overall, I'm proud of the organization's response to COVID-19 crisis.
We have a strong capital position with more than $595 million on our balance sheet as of the end of first quarter. We're being both strategic and prudent about capital allocation. As an example, because of COVID's potential impact, we have deferred certain capital expenses at our Hopewell facility and now anticipate that GMP manufacturing of clinical material at this facility will begin in early 2021. I also want to highlight other aspects of PTC business that keep us well-positioned, both in the crisis and beyond. These include the strong team that we have in place, our global commercial infrastructure, and commercial products that can be delivered and administered to the patients at home. For the first time, SMA patients will have the potential opportunity for an at-home therapy. In addition, we have a diverse, rare disorder pipeline with multiple upcoming catalysts.
Let me now focus on the progress we made during the first quarter. Starting with SMA, we recently disclosed the meaningful and positive results for risdiplam in both the SUNFISH pivotal study for type 2 and 3 SMA patients and the FIREFISH pivotal study in the type 1 SMA patients. We anticipate an approval with a broad label later this year. Earlier this week, along with our partners, Roche and the SMA Foundation, we shared the positive 12-month results of the FIREFISH Part 2 pivotal study. The FIREFISH Part 2 study results are quite exciting and show the importance of increasing SMN protein systemically, demonstrating achievement of motor functions and developmental milestones such as ability to roll over, sit, and stand. The study met its primary endpoint of patients sitting without support at 12 months and was highly statistically significant.
12 of 41 patients, or 29%, met the milestone with a p-value of less than 0.0001. Considering the median age at enrollment was 5.3 months and that these infants already had progressed disease, these results are particularly exciting. The safety data were consistent with the known safety profile of risdiplam. Importantly, this study also met all its key secondary endpoints. This included the CHOP INTEND , HINE-2, and event-free survival. 90% of all infants in this study showed CHOP INTEND improvement from baseline, with a median change from baseline of 20 points. Part 2 showed even greater improvements in patients' ability to stand and walk as assessed by HINE-2 than were observed in Part 1 at 12 months. One patient in FIREFISH Part 2 reached the bouncing milestone, a key component of developing the ability to walk.
After 12 months of treatment with risdiplam, 93% of infants were alive, 85% were without permanent ventilation, and 95% of patients maintained the ability to swallow. As Dr. Servais pointed out on the Roche call, this is particularly impressive when compared to other therapies as the bulbar function benefits may reflect a small molecule's ability to reach the brain stem. In contrast, in the natural history of the SMA type 1, the median age of death or permanent ventilation is 13.5 months, and all infants with type 1 SMA older than 12 months require feeding support. Overall, it's clear that these results are highly compelling. As we communicated recently, the FDA extended the PDUFA date of risdiplam to August 24th due to the submission of additional data from SUNFISH Part 2.
The inclusion of these data in the submission is anticipated to support broad access and reimbursement to risdiplam for the widest range of SMA patients. Importantly, the FDA has identified no substantive issues to date during the review. Roche's careful preparation has assured ample risdiplam drug supply. Roche is working proactively with its partners in the SMA community and its logistic providers to ensure drug supply upon launch in the current COVID-19 environment. As part of Roche's pre-launch commercial efforts, several early access programs have been initiated. Earlier this year, early access programs were open in the United States and European countries for type 1 SMA patients. Recently, it was announced that the program is being expanded to include type 2 SMA patients.
Importantly, in response to requests received from type 1 and type 2 patients whose current treatment has been interrupted as a direct consequence of the COVID-19 pandemic, Roche has decided to amend the programs to allow for these patients to be able to receive risdiplam. These requests for risdiplam demonstrate that a significant unmet need exists within the SMA population. The need for an oral therapy that is taken at home is shown to be even more critical for patients as they try to navigate through the COVID-19 pandemic. In fact, risdiplam would be the only available SMA therapy that does not require clinic visits for administration, an important concern for patients with respiratory complications. We expect that risdiplam will be the most competitive global product for a broad range of SMA patients and anticipate a robust launch following approval. Risdiplam was the first compound arising from our splicing platform.
One advantage of being an oral compound is that it's systemic, so that it is in the blood and can get to all affected tissues. A second advantage is the ability to measure risdiplam's pharmacodynamic effect on SMN2 mRNA and SMN protein in blood or other easily accessible tissues. As you may recall, we successfully utilized this approach in risdiplam's phase I studies, where we demonstrated proof of concept of its activity in healthy volunteers. We plan to use this same approach in other splicing programs. This same approach will be used in PTC-518 in Huntington's disease. PTC-518 is a development candidate from our Huntington program, and IND toxicology studies are ongoing. Let me now turn to our commercial efforts in the first quarter. We had a strong year-over-year first quarter growth with our DMD franchise, with revenues of $68 million.
We are reporting $40.5 million in worldwide Translarna sales and $27.5 million in U.S. EMFLAZA sales. In addition, we continue to see positive trends in the weeks following the first quarter. Nevertheless, we cannot predict the duration and severity of the COVID impact on our commercial business over the coming months. Therefore, until we have further understanding of the effects of COVID and on our revenues, we are withdrawing our 2020 financial guidance at this time. I also want to talk about Analyst Day. It's becoming increasingly clear that hosting an Analyst Day in mid-June in New York City would not be in the best interest of the health and safety of either our employees or guests. We will postpone the meeting and switch to hosting multiple webinars in which we do deep dives into our programs and platforms.
We'll be shortly posting the date of which the first deep dive will occur. We believe this will be a productive way to update you on all our programs and platforms. I'll now turn the call over to Matt and Eric and Emily. For Matt and Eric, we welcome them to the executive team and their first debut on the quarterly calls. Matt will now update you on the status of the clinical programs. Eric will cover more on the commercial business update, and Emily will give a financial update. Let me now turn it over to Matt. Matt?
Thanks, Stu. I'm thrilled to join the executive management team at PTC, and I look forward to the continued progress of our clinical programs. It's an exciting time to step into this role with our multiple upcoming clinical catalysts, even in light of the current environment. In terms of timing updates for our clinical programs, I will start with the Study 045, the U.S. Translarna Dystrophin Study. Due to COVID-19, the 045 study site is closed to elective procedures, which has delayed the study completion, as a few patients still require final study muscle biopsies. Based on the site's current timelines, we now anticipate reporting top-line data in the third quarter. We expect that in combination with our existing clinical data, statistically significant results in 045 would be sufficient for accelerated approval in the U.S.
As a reminder, this is a single-site, 40-week study that enrolled 20 boys aged two to seven years with nonsense mutation. The primary endpoint is percentage dystrophin change from baseline as measured by electrochemiluminescence, or ECL. In close collaboration with the FDA, we developed and validated an ECL liquid-based assay that is highly sensitive, highly linear, and particularly well-suited to identify large proteins such as full-length dystrophin. Turning now to our splicing platform, Stu detailed the exciting results for risdiplam, our first small molecule from this platform. Our next splicing program in Huntington's disease remains on track, with initiation of clinical studies in healthy volunteers to start prior to the end of the year. These phase I studies will include both single and multiple ascending dose regimens in order to inform safety and pharmacokinetic parameters.
We expect these studies will be relatively straightforward and support dose selection to achieve target Huntington's RNA reduction levels in the range of 50%. Shifting to our Bio-E platform, due to COVID-19, we now expect to initiate potential PTC-743 registrational trials in refractory mitochondrial epilepsy in the third quarter and in Friedreich ataxia in the fourth quarter. We will initiate these studies once the planned study sites reopen and are available for clinical trials. Of course, once we can ensure patients can safely travel to and from study sites. The Phase I trial of PTC-857, which is being developed for GBA-associated Parkinson's disease as its first indication, remains on track to start in the third quarter. As we have discussed previously, the Bio-E platform is complementary and synergistic with our other platforms.
PTC-743 and PTC-857 target 15-lipoxygenases, a key enzymatic hub that regulates the inflammation and oxidative stress that underpin mitochondrial and CNS disease pathology. PTC-743 has been tested in over 400 patients, primarily in children with inherited mitochondrial disease, and has demonstrated promising efficacy as well as favorable safety signals. In expanded access and compassionate use studies in patients with mitochondrial disease, PTC-743 has had a clear impact on refractory seizures, reducing the number of patients' seizures as well as seizure-related morbidity, including hospitalizations. In a phase II trial in Friedreich ataxia, PTC-743 demonstrated statistically significant impact on disease severity at 24 months relative in age and stage-matched natural history controls as assessed by the validated FARS score. For PTC-857, the compelling preclinical data and its target and mechanism of action strongly support its development for Parkinson's disease.
The target of 15-lipoxygenase is a very important upstream modulator of multiple pathways known to be key to Parkinson's disease pathogenesis, including alpha-synuclein oxidation and aggregation and microglial activation, a driving factor in neuroinflammation. Therefore, targeting 15-lipoxygenase allows us to simultaneously affect multiple pathways, while many current therapies in development target only one of these pathways. Moving on to our gene therapy platform and associated updates, as Stu noted, COVID-19 has impacted our gene therapy program timelines. With respect to the Friedreich ataxia and Angelman syndrome gene therapy programs, COVID-19 has impacted multiple IND-enabling activities. We currently anticipate the IND filings will be delayed at least one quarter, and we plan to provide an update on filing timing as we better understand the ultimate impact of COVID-19 on these programs. Moving to our AADC deficiency program. Manufacturing activities are continuing and remain on track.
The gating factor for the BLA submission remains the study of the use of the commercial cannula in young patients. These treatment procedures have been delayed by hospital cancellations of elective procedures due to COVID-19. We now expect the BLA submission for AADC deficiency to the FDA will be in the second half of 2020. As a reminder, the MAA for the AADC deficiency program was submitted to the EMA in January, and timelines remain in place for the CHMP final opinion by the end of the year. Overall, despite COVID-19 related delays, we still expect a number of exciting and impactful clinical catalysts in the coming months. I will now pass the call to Eric Pauwels to provide an update on the commercial business.
Thanks. To echo Matt Klein's comments, I am delighted to join the executive management team at PTC. With a strong first quarter behind us and important upcoming milestones this year, we will continue to build on our existing portfolio of revenue-generating products, prepare for future launches, and remain selective with business development opportunities. Currently, on the commercial side of the business, our top priority is ensuring that patients on treatments have the necessary drug supply, and we have not seen significant disruptions to date. With personal promotion from our sales team worldwide, limited by COVID-19, we continue to engage with healthcare providers, patient advocacy groups, and payers by driving DMD disease awareness activities through virtual calls, DMD master class webinars, and educational podcasts, as well as leveraging virtual platforms to host local advisory boards.
Social media is playing an even important role in the current environment, especially for DMD patients seeking information about our products. We had a solid first quarter with Translarna and EMFLAZA, both in terms of maintaining our existing patients, and in new patient growth. New patient growth was driven in part by diagnostic and educational efforts over the last several months, we continue to see these efforts positively impacting the business into the second quarter. For Translarna, we saw continued growth in Q1 and positive trends both in diagnosis and prescriptions globally. In the EMEA region, we have successfully maintained adherence and compliance with patients on Translarna and have seen minimal disruption.
In the LATAM region, we continue to have ongoing discussions with the Ministry of Health in Brazil to secure future purchase orders. We have seen the number of positive injunctions that will allow patient access to increase. Importantly, we continue to highlight comparisons of the impressive real-world results from the STRIDE registry and SYNERGY DMD Natural History Study, highlighting the long-term efficacy of Translarna. For EMFLAZA, our U.S. commercial and PTC cares case management team has been fully engaged and made significant impact in the first quarter of 2020, driving enhanced customer service and improving efficiencies with new patient starts, reauthorizations, and patient adherence and compliance. We expect these ongoing improvements will continue through the next quarter.
In the first quarter of this year, patients moved faster from time of new prescription to commercial therapy, and patients previously on bridge therapy and patient assistance programs transitioned to commercial therapy more rapidly. Physicians continue to see the differentiated benefits of EMFLAZA, continued by multiple publications, including the recent data from Cincinnati Children's Hospital real-world outcomes demonstrating EMFLAZA's benefits, such as delaying loss of ambulation better compared to prednisone. Let's turn to Tegsedi. Our launch activities are still progressing despite the current environment, with our focus now on pricing discussions in Brazil, which we expect to be completed in the second quarter. Tegsedi is well-differentiated as the first and only approved at-home therapy in Brazil, with slowing disease progression and quality of life indicated in the label. In the first quarter, we saw continued growth in new patient identification and prescriptions in LATAM.
As a reminder, Brazil has the largest prevalence of hATTR amyloidosis polyneuropathy patients worldwide. Building on our core capabilities in LATAM, we anticipate a Waylivra filing with ANVISA in the second half of this year and continue to identify new FCS patients for Waylivra therapy. Turning to AADC Deficiency, pre-launch activities continue to progress. We have adapted to the current environment by implementing virtual education and patient-finding initiatives. Including conducting multiple master classes with over 200 healthcare providers in attendance from over 20 countries. We also rolled out a program called The Road Less Traveled for finding a path towards early patient diagnosis. We've also held multiple European steering committee meetings. We recently launched social media campaigns utilizing expert videos, focusing on symptoms, and directing viewers to disease state websites.
Finally, patients continue to be identified as our teams push forward with virtual healthcare provider meetings to diagnose new patients in cerebral palsy and epilepsy clinics. Looking back at the quarter, the home-based administration of our commercial products allowed us to maintain our current base of patients and add new patients, even as the COVID-19 pandemic started to take hold. As a result, in the near term, we anticipate continuity of supply to the existing base of patients, some continued growth with new patients for both Translarna and EMFLAZA, and continued operational improvements. I will now hand the call over to our Chief Financial Officer, Emily Hill, to review our financial progress.
Thanks, Eric, and congratulations to Eric and Matt for their promotions. We are happy to have you on the management team. We are also happy to have reported such a strong first quarter, with our DMD franchise growing 28% year-over-year, and with the positive tailwinds from the first quarter continuing into April. We feel well-prepared to handle the current environment, as we have highlighted this afternoon, but due to lingering uncertainty regarding the duration and the degree of the impact of COVID-19, we are withdrawing financial guidance for 2020. As you have heard reflected throughout today's call, we have given a great deal of thought to costs, timelines, and prioritizations throughout the COVID-19 pandemic. We are fortunate to have a portfolio of home-administered commercial products, diverse assets across multiple platforms, and the ability to shift resources as needed.
Strategically, we have identified trade-offs where we can push forward certain programs and be more conservative with capital-intensive programs, such as deferring some capital expenditures for our Hopewell biologics manufacturing facility for future commercial products. This doesn't impact our production of near-term commercial and clinical programs such as AADC deficiency and Friedreich ataxia gene therapy but allows us to conserve some cash as we move through this uncertain time. I now want to take a few minutes to highlight the first quarter 2020 financial results. The press release issued earlier this afternoon summarizes the details of our first quarter 2020 financial results, I will review these details now. Starting with our top-line results, we reported $68.3 million in total revenues in the first quarter of 2020 compared to total revenues of $53.6 million for the first quarter of 2019. Translarna net product revenues were $40.5 million for the quarter.
This compares to $35.3 million for the first quarter of 2019. Growth was driven by an increase in net product sales in existing markets, as well as continued geographic expansion into new territories. For EMFLAZA, we reported net product revenues of $27.5 million for the first quarter of 2020 compared to $17.8 million for the first quarter of 2019. Growth was driven by an increase in net product sales due in part to the operational improvements and efficiencies noted by Eric earlier. Non-GAAP R&D expenses were $81.9 million for the first quarter of 2020, including $8.2 million in non-cash stock-based compensation expense, compared to $47.9 million for the first quarter of 2019, excluding $4.7 million in non-cash stock-based compensation expense. The increase in R&D expense reflects costs associated with advancing the gene therapy and Bio-E platforms and increased investment in research programs, as well as advancement of the clinical pipeline.
Non-GAAP SG&A expenses were $51.2 million for the first quarter of 2020, excluding $7 million in non-cash stock-based compensation expense, compared to $36 million for the first quarter of 2019, excluding $4.6 million in non-cash stock-based compensation expense, reflecting continued investment to support our commercial activities, including our expanding commercial portfolio. Net loss was $112.7 million for the first quarter of 2020 compared to net loss of $72.1 million for the first quarter of 2019. Cash, cash equivalents, and marketable securities totaled $595.9 million at March 31st, 2020, compared to $686.6 million at December 31st, 2019. Before I wrap up, I wanted to share the details of a transaction we completed this week with the former shareholders of Agilis that removed liabilities from our balance sheet. As you are probably aware, as part of our acquisition of the gene therapy platform, we owed Agilis future cash milestones.
We are pleased to have exchanged a subset of those cash milestones for cash and PTC stock. The future milestones include $40 million of time-based milestones that were owed in August 2020 and $185 of cash milestones we expected to pay in 2021 upon the approval of the AADC deficiency BLA and the receipt of a priority review voucher. Almost 95% of former Agilis shareholders elected to exchange those 2021 milestones for approximately 2.8 million shares of PTC stock and an early receipt of the 2020 cash. This alleviates PTC of significant cash liabilities, especially in 2021 while we advance our gene therapy platform. I will now hand the call over to the operator to start our question and answer session. Operator.
As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is now open.
Hi, this is Bert on for Brian tonight. Congrats on all the progress and your handling of the COVID situation. I just wonder if you could talk a little bit about how much progress you've been able to make on the additional study of the AADC gene therapy, and catheter combination prior to the pandemic, and then I guess what types of data from that study do you need to complete the filing?
Yeah. Hey, thanks for that question. Yeah, we were making progress with the AADC clinical trial. Matt, why don't you actually talk through what we were doing and the next steps?
Thanks, Stu, thank you for the question. As you mentioned, towards the end of 2019, we had received feedback from the FDA on additional data around the use of the intended commercial cannula in young patients. As a reminder, the clinical efficacy in our AADC deficiency program is quite strong. We've demonstrated durable impact with five years of continued effect, as well as evidence of continued benefit out to ten years. We, of course, have a strong safety profile. Manufacturing also remains on track, and we were able to submit the MAA to the EMA in January. The key gating item for the BLA was the treatment of young children with the commercial cannula. We had identified two patients that we were prepared to treat before the end of the first quarter.
Due to the hospital closure for elective surgeries, those procedures have been pushed back, likely, to be done sometime towards the end of Q2, possibly early Q3. Once we have those surgeries and the data from that, we'll be able to continue our preparations for BLA submission.
We made pretty good progress.
Great.
Just the pandemic fell upon us. That did just take a little time to move forward on.
Great. Thank you so much.
Our next question comes from the line of Alethia Young from Cantor. Your line is now open.
Hi there. This is Lee on for Alethia. Thanks for taking our questions. I guess the first one is on COVID-19. Just wondering, are you seeing any changes in buying patterns for Translarna? How do you manage to keep the access for patients? Second, for the FIREFISH data, how do you think risdiplam matches up to Spinraza and Zolgensma in type 1 patients? For the SUNFISH data, is there any plan to present subgroup analysis, particularly around age from the dataset? Thanks.
Okay, great. Well, thank you. Maybe we'll start with the first one, which is on Translarna, for that matter, EMFLAZA as well. I think you could see from the numbers, we had actually a good first quarter, and I think as both Eric and Emily talked, we saw the numbers continuing on. The distribution remains ongoing. I think we feel patients have been able to put in the order. Eric, maybe you want to talk a little bit about how you see what's coming up for the next quarter or two.
Yeah, sure, Stu. Thanks for the question. We're seeing continued growth in the number of patients on both products with DMD, Translarna and EMFLAZA. We haven't seen any actually decline in orders. Actually what happens is we've actually been able to establish even deeper relationships with our healthcare providers and in some cases, payers and advocacy groups during the pandemic. I think our main focus right now is really to provide that current base of patients we have on EMFLAZA and Translarna, a continuity of supply. We haven't seen any sort of major upticks if the question is centered around are people asking for multiple months. There have been a few patients that have asked for 90-day supplies of EMFLAZA, but generally, the vast majority of patients have been getting monthly supplies in the quarter.
That may tick up a little bit, it's not very significant. Most importantly, we've been able to really establish our case management team in the U.S. has been able to establish a strong sort of connection with many of the DMD patients to ensure that they have all the resources they need, and assure them that we have adequate supply of both EMFLAZA and Translarna.
Yep. The second question relates to risdiplam and in a sense, to contextualize how we feel risdiplam will do, relative to the other products that are out there. It's really our contention that risdiplam is the best-in-class molecule with efficacy potential. I think what you could see from the recent FIREFISH data is both Part 2 but as well Part 1, that this was compelling efficacy that was seen in that. Not only did we see that, but we're able also to show durable increases in the SMN protein and changes in the RNA, both in the CNS as well as the periphery. That's actually really critical. I think we're the only ones who've been able to show that.
Not only we showed that, but it was in the periphery, and not as much has been talked about of how SMA, but it's becoming clearer and clearer, is a whole body disease. While the CNS is critical, it also affects other tissues as well. We think another advantage is that it's really the risdiplam itself that is the treatment. You don't need an intrathecal injection for that, nor do you need to take immunosuppression as a consequence of taking the drug. We think that's really a major advantage. We also think that so far, what we've seen to date was that there was no drug-related safety findings, and that we're very proud that we've had the broadest clinical trial program thus far in treating patients in SMA 1, 2 and 3.
Patients from two to 25 years old, where we've had placebo-controlled trials there. We also have pre-symptomatic to older adults, so from naive to pre-treated. We really have a breadth of program to demonstrate the efficacy of that, and has shown that both in the placebo-controlled SUNFISH trials as well as in the risdiplam trials. When you contrast that, say to gene therapy, I think is what you asked for, that we think that there's little data beyond three years in terms of durability. Even that, we think is potentially confounded by the follow-on therapies that were used that confound which drug did what in terms of keeping the patient well. We think there were more safety concerns in terms of both the liver injury warnings, systemic corticosteroids are needed, and that you need to be on immunosuppressants for greater than two months.
It's not approved for all populations, and there's limited data in patients greater than two years old. Taking that, we even think when you compare it to nusinersen where the burden of intrathecal administration is more difficult in patients, say, with scoliosis. You have continuous accumulation of lumbar punctures. There have been meningitis and hydrocephalus that's been observed on the safety front, and that there's a lack of trial data in patients greater than nine years old. We think if you take all that into consideration and look at what risdiplam has done in the whole patient population, again, we think it's the best-in-class molecule. I think you had one other question too.
Yeah, the SUNFISH. Yeah.
Yeah. I'm sure we'll be having additional posters over time on the data as it accumulates.
Okay, great. Thanks.
Thank you. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open.
Hi. Good afternoon, guys. Thanks so much for taking my questions. Maybe one on AADC. Then I have a couple more on a couple of other programs. Stu, in the past, you had been starting to give us updates on number of patients that you've been able to identify. Can you give us a refresh number on how many patients you have as of today? Also, whether your thinking still is that they're around, let's say, 6,000 patients worldwide that you hope to find over the course of the next several years.
Great. Thanks for that. I'd say that as we said in January, we had greater than 200 patients identified at the JP Morgan meeting. We continued to search. We obviously have some issues as a consequence of COVID-19, and I'll have Eric talk a bit about that. We're still comfortable with the numbers that we said that we think is there. Now it's really a matter of patient of identification, and then to do so right now in the COVID-19 environment is obviously more difficult than previous. We're still working hard at that. Eric, maybe why don't you talk a little bit about how we're doing this in the current environment.
Sure. Stu. Hi, Tazeen. I think right now it's pretty safe to say that the COVID-19 environment has had a direct impact on patient identification efforts. We're doing a lot of activities right now and adapting to this new environment. As Stu said, we've identified more than 200 patients at this point, and our goal is to actually get 300 patients identified by the first country launch, whether that's in the U.S. or Europe. We have had a number of different initiatives, particularly in Q1, and when things started to slow down a little bit, we shifted, and we increased our web presence and online efforts substantially. We had a master class that had about 200 healthcare provider physicians in 20 countries.
We rolled out this program that was very well received called The Road Less Traveled, and it really helped healthcare providers to understand how to diagnose AADC deficiency patients earlier, as well as recognize various symptoms, particularly in areas where we're trying to target right now to cerebral palsy clinics and epilepsy clinics. In addition to that, we've actually rolled out quite a few of the European AADC Steering Committee meetings, and we executed quite a number of those and had surprisingly really good reception from key opinion leaders in these virtual education classes to help with patient identification. Now, with all that said, it's clear that COVID-19 has had an impact given that fewer patients are seeing physicians and tests are being done. We're still doing quite a bit of activity virtually to keep up the educational noise level.
Okay. Thanks for that. Maybe still a question on Translarna. For the study that you're doing to measure dystrophin, can you give us an idea of what percent of patients have not yet received that biopsy? Does it make any meaningful difference if, let's say, a patient was scheduled to get a biopsy in March or April, but they don't end up getting it until May or June?
That's a good question. Probably we've gotten, I'd say we're waiting to get the last biopsy on approximately 40% of the patients, somewhere around there. They were all scheduled to come in, this has sort of interrupted that. We don't think there's a real issue in terms of the biopsy for treating them longer. We don't think that will be a real problem. Right? We should be able to, once the sites are back and running and open, be able to get this accomplished. We don't think that'll be a big deal.
Okay. Is this something that you've discussed with FDA, this delay?
I think in general, they know that sites are having issues. I don't know if we've actually talked to them directly, but they put out things already about when, because they know some sites that just closed down, especially in metropolitan areas. In this particular case, you might recall from the Sarepta case that they actually had a 9-month and an 18-month. We don't look at this as a real issue.
Okay. Thank you.
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Our next question comes from the line of Joel Beatty from Citi. Your line is now open.
Hi, thanks for the question. Risdiplam launches, should we anticipate that payers will only cover it as a monotherapy, or could there also be situations that payers could be open to paying for it as combo therapy with Zolgensma or Spinraza?
Maybe a couple of points to think about. You got to remember that, let's start with risdiplam with Spinraza. We don't understand actually why that would occur necessarily, because they both sort of promote this alternative splicing into the SMN transcript. I think, and we've shown pretty clearly that you can actually make all of the SMN2 RNA into the appropriate RNA to make the protein. Risdiplam does a very good job in terms of being able to make the appropriate RNA and therefore protein.
In the case of Zolgensma, our guess is that we'll be competing with them in order to get type 1 patients. My guess is that as patients feel a need to get additional treatments, and we know from our trial that we currently have, that there are patients from Zolgensma who are now on our open label trial, who are now getting risdiplam as well. We would anticipate that there'll be patients who probably would want to get risdiplam as well, especially in the light of we don't know how durable or the variability of how patients do when they get this.
Makes sense. One more question on risdiplam. Are there certain regions that you anticipate have a little bit more favorable dynamics for more rapid launch than other regions? What type of factors would help a region have a rapid launch of risdiplam?
I think that obviously Roche is in charge of commercialization, they're certainly going to want to get moving rapidly in the U.S., and then really throughout the world will want to be done. The U.S. is the first country that they would go for. The other point, actually, I wanted to make on the previous question also was that when I think about it, there were precedents in where Spinraza was covered after Zolgensma. I think certainly that also goes along with the notion of we anticipate that risdiplam would probably be used even if Zolgensma was used.
Great. Thank you.
Thank you. Our next question comes from the line of Joseph Thome from Cowen and Company. Your line is now open.
Hi there. Thank you for taking my questions. The first one on the GMP manufacturing in early 2021. Can you articulate how this maybe slight delay would impact any sort of initiation of gene therapy studies if those are tied together? My second question is, it looks like there is a study on clinicaltrials.gov for Translarna in DMD patients aged six months to two years. Wondering what you're hoping to show here, and is this related to a potential U.S. submission or the ex-U.S. label? Thank you.
Sure. Yeah, thanks. The GMP manufacturing, in terms of Hopewell, I was really just because of when we were thinking about COVID-19, we already started making toxicology levels of material in the Bridgewater site. Based on being able to do that, we don't anticipate really it'd be slowing it down in any way. It allowed us to just defer the opening of the plant till we get to 2021 in the current environment we have, so there'll be no delays as a consequence of pushing it forward by four months. We didn't think it was a real issue, and it conserved a considerable amount of cash. We thought we might as well do that since we already created the tox batches in our Bridgewater site.
In terms of the six months to two years of age, it's really just to get the extension. We've done the work, and we did that, and we've gotten that actually, approval in the U.S. I mean, in Europe, sorry, to expand the label so that people with nonsense mutations can get it earlier. That's what we've worked towards. That's just to continue to get earlier and earlier patients in.
Great. If I could just do one more on AADC. I see you're having some data presentations at ASGCT to outline changes on the Peabody Scale and HINE-2 and sort of functional endpoints. In terms of the regulatory review and maybe what physicians are interested in, how are they each going to look at these different efficacy endpoints? Is there one that's most important, or do they look at them kind of holistically?
Sure. Matt, do you want to take that?
Yeah, sure. Thank you, Joseph, for the question. I think when we think about the AADC data package, first what's very important is the fact that we're able to show on PET scan that there is a significant increase in dopamine production in all the patients. That's the first very important sign that we're addressing the critical underlying biochemical defects. That's very compelling evidence that we're really targeting the fundamental pathology of the disease. As you look at the data package in its whole, including the primary endpoint of head control, we're able to show that there's benefit in every patient treated. What we're now seeing with the long-term data, as shown in some of the abstracts you mentioned, is that we're seeing durability of effect out past five years, even close to 10 years in some patients. That's a very strong, compelling data.
What we believe is that physicians will appreciate the totality of the data, that one, we're addressing the fundamental biochemical defect in all patients, and two, across the board, we're seeing correction and evidence of correction of the key motor function defects in the disease, and that those favorable effects are sustained.
Great. Thank you so much.
Thank you. Our next question comes from the line of Vincent Chen from Bernstein. Your line is now open.
Congratulations on all the progress. Thanks for taking the questions. A couple from me. The first one is just on, I guess, revisiting the COVID-19 impact. I was wondering if you could elaborate a little bit further on what impact you've seen so far as far as slowdowns related to COVID. It sounds like the franchises have been pretty resilient so far, and I have to imagine the worst has largely been in April, yet the decision was made to withdraw guidance given potential COVID-related impacts. Just want to get a better sense for whether you're indeed seeing any slowdown in demand for current and market products over the course of the last couple of months, whether end of Q1 or in April to date. Or is it pulling guidance just in case things were to get worse going forward?
Okay. Yeah, that's a good question because the pulling of guidance is more on, or withdrawing it at the moment is really on the uncertainty of where things are going to go in the long term. You just don't know. I would say in the short term, we feel pretty good where in the first quarter and even after how things look in terms of maintaining the patients already on drug and even seeing new prescriptions. It wasn't like we saw a slowdown and maybe, Eric, maybe you want to put a little bit around this a bit.
Yeah, sure, Stu. Yeah, Vincent, thanks for the question. In terms of the top line, we've seen the trends right now, both in Europe and Latin America that are very encouraging still. As I mentioned, we haven't had any kind of increases at all, patients asking for more product. We've been shipping most of the patients on a month-to-month basis. We continue to see those positive trends in Q2. The existing patient base and new patient growth is still there, although new patient diagnosis and new prescriptions have decreased a little bit now as we've seen because patients are not seeing a physician as frequently. We have protected the base, which is very good, and the trends are good there. We have gone back to make sure that everybody realizes we have an adequate amount of supply. There have been some requests, in addition to the uptick.
There have been a few patients, and we're seeing more and more requests for potentially 90 days of supply for EMFLAZA, but it's still a small percentage. I think what we're concerned more about is the unknown. I think as Stu highlighted, if the pandemic continues and there's a shift of unemployment and payer mix or potentially disruption to some of our Translarna shipments that might be in various markets, keep in mind we have patients in close to 50 countries with partners as well as direct business. If some of that is disrupted because of the pandemic, at this point in time, we're just trying to be cautious. There's no indication now that, based on our strong results in the first quarter and what we're seeing so far right now, that we're losing patients or that that growth would go down.
I'll give that back to Stu.
Maybe one quick follow-up on that point. If you think about the price for EMFLAZA in the U.S., how does the price paid for EMFLAZA differ between patients on commercial insurance and patients who are on government insurance? Taking another way, if you were to see a meaningful shift in payer mix, how might that impact the net price paid on average?
Yeah. Well, the simple answer is it's basically the statutory rebate from CMS, which is higher right now. Our current payer mix is about sort of 60/40, with commercial payer being the majority. If obviously that shifted, our gross to net would shift because there would be more patients moving on to Medicaid. Far we haven't seen that, and it seems to be that DMD families in general have pretty good insurance and have cover. In addition to that, if patients do go from private payers to Medicaid programs, a number of the states actually have disability programs for children, and they can move very quickly. Again, I think the only effect there, Vincent, would be the statutory rebates that we would have to pay to CMS if the payer mix shifted.
I see. If I could ask another one just on Translarna and the ongoing study. I was just wondering if you could give us a sense for how the powering calculations were done in terms of choosing the number of patients in the ongoing U.S. dystrophin study. What data did you have sort of draw upon in terms of estimating the likely effect size? Is there data you've collected from other patients treated with Translarna to see just how much of an increase you see in dystrophin, whether from your studies or from clinical experience, I guess in territories where Translarna is used?
Yeah. Thanks for that. That's a good question. We did look at other studies as well. It was based on data that we saw from Sarepta and from just making some assumptions based on that and what the assay is like that we got there. Matt, is there anything else you want to add to that?
Yeah, just that we believed with the 20 subjects in the trial that we would be able to achieve. We had 90% power, which we thought would be sufficient to show the Translarna effect. Of course, we expect a baseline to be very, very low levels of dystrophin expression.
When you say 90% power, could I ask, what was the estimated effect size and the variability?
Correct. As Stuart said, basically looking at other trial data and running simulations.
Okay. Thanks for taking all the questions.
Thank you. Our next question comes from the line of Gena Wang from Barclays. Your line is now open.
Hi. This is Peter for Gena Wang. Thank you very much for taking the question. I guess my question is on risdiplam. I guess, do you expect risdiplam to generate meaningful revenue this year or do you anticipate some patient initiation impact to COVID? My second question on a related note is, could you remind us when the EAP was opened and how many patients have been sort of enrolled in U.S. and OUS and whether pre-COVID and post-COVID, the EAP enrollment rate has sort of changed? Thank you.
Sure. Maybe the big picture on COVID and revenues. I think on the big picture on COVID, in some ways, I think people will start thinking about how do I make sure I have drug supply to patients. I think in some ways it might be helpful from a commercial launch perspective. I think in terms of revenues, that would be royalty. Maybe Emily, you want to talk a little bit about that?
Sure. We have the potential for up to $42 million in milestones this year on our collaboration with Roche on the risdiplam program. Obviously, tiered royalties up to the mid-teens. With the MAA having been submitted earlier this year and the PDUFA in the U.S. now in August 24th, I'd expect those to ramp up more significantly next year. I think as far as COVID's impact, the rate and ramp of those revenues, there's really some advantages in potentially being the only SMA therapy that can be delivered at home.
Yeah. The patient numbers, well, I don't think Roche yet has discussed that, but I think what they did say on the call previously and what they have said is there's a lot of interest, and so they are bringing patients in that are already on the EAP, and they're continuing to do that both in the U.S. as well as then to set it up also in Europe as well. It'll be a global, in a sense, EAP program. Certainly in the U.S. all over and then in countries that allow you in Europe to have these EAP programs.
Got it. Thank you very much.
Thank you. Our next question comes from the line of Raju Prasad from William Blair. Your line is now open.
Thanks for taking the questions. On risdiplam, when do you anticipate presenting additional JEWELFISH and RAINBOWFISH data? Aside from what you've already mentioned, do you have any general commentary on how many patients Roche is bringing in on the expansion of the EAP or any details around what types of scenarios that they are expanding it to? Is it just if patients are off Spinraza or don't want to go in, they apply, or is there more stringent criteria? I have one on Translarna.
Sure, yeah. That's an important point, too, is that they are now planning presentations for that. It will probably be an update on the Cure SMA. Yes, they have changed the EAP Program to allow patients who are on other therapies to get into the EAP Program as well. They've also added type 2 as well to the program. Yeah. Patients who can't get, say, intrathecal injections or naive patients, they certainly can. It's really based on the physician's discretion based on what they think the need is. COVID-19 is obviously making limited access, so this is really a nice way in which they can get it at home and take it. That's also adding to the number of patients who are hopefully transitioning to risdiplam. Very strong interest in this stuff.
Yeah. Do you have any idea of how many in the U.S. versus E.U. are getting on the early access program, just kind of a general percentage-wise?
No. Yeah, that hasn't been disclosed yet.
Okay. One on Translarna, and then obviously you pulled guidance and you commented on it enough on this call, but just wondering, usually you have a kind of Q2, Q4 bolus from Latin American orders. Is the general pattern of revenue recognition going to be similar?
Yeah. I think maybe Eric could comment on that.
Yeah, sure. With regards to Latin America for Translarna, as you can recall, we had approval from ANVISA last year, we've been building a very nice base of patients. We saw new patients coming in in the first quarter. Not only diagnosing these patients, new prescriptions, the base of patients that received positive injunctions for therapy continues to increase. We've seen growth on all those parameters. With regards to that base, we have ongoing negotiations with the Ministry of Health and with ANVISA to require that we get those group purchase orders. We're working towards securing a group purchase order in the second quarter. We've shifted a lot of our virtual communications right now with the Ministry of Health because of COVID-19 to virtual-type meetings, we continue to have a very strong working relationship with the payers in Brazil.
Our goal is, as we've seen continuous number of increases in patients right now, our goal is to get and secure an order for Q2, barring any kind of exceptional acceleration of the pandemic or some kind of government diversion of resources. You got to keep in mind, though, that the rare disease bucket for cost centers at Ministry of Health is relatively small in comparison to the overall healthcare budget. We think we can work through some of these things and negotiate and hopefully obtain an order in Q2 and ensure that patients' continuity is there. Again, we're very encouraged with the continued growth, and it's going to continue to put pressure on the Ministry of Health to secure those orders.
Great. Thank you.
Thank you. At this time, I'm showing no further questions. I would like to turn the call back over to Stu for closing remarks.
Okay. Well, look, I want to thank all of you for joining the call today. I want to remind you that at the end of March was our 22nd anniversary at PTC. As I look back upon now our long history, I'm very proud of how the company has evolved. It's gratifying to see the progress that we've all made and continue to make in discovering, developing, and commercializing treatments for patients living with rare disorders. I think really a consequence of the hard work and dedication of the team, we're well-positioned to be able to push forward and even thrive, even under these uncertain environments. Again, thank you for joining the call. I look forward, I hope, to see you all soon.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.