Good day, ladies and gentlemen, and thank you for your patience. You've joined the PTC Therapeutics 2019 First Quarter Corporate Update And Financial Results Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer and instructions will be given at As a reminder, this conference may be recorded. I would now like to turn the call over to your host, Head of Investor Relations, Emily Hill.
Ma'am, you may begin.
Thank you. Hello, good afternoon, and thank you for joining us to discuss our 2019 first quarter corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcio Souza, and our Principal Financial Officer, Christine Otter. Before we start, let me presentation, 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 and uncertainties, we encourage you 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 for today's earnings release. Before I hand the call over, I would like to point out that given the data from our SMA program will be presented next week at the American Academy of Neurology, We will not be making any comments on that program today. With that, let me pass the call over to our CEO, Stuart Peltz.
Thanks, Emily. Thank you for taking the time today to be on our call. PTC has had a very productive start to 2019. We continue to execute on our strategic vision. Importantly, Translarna was approved this week by the Brazilian regulators.
This enables faster market expansion to DMD patients in Brazil. This is the largest independent regulatory authority outside of the EMA to validate the risk benefit of Translarna which serves patients around the world. Our current commercial sales continue to provide us with a strong base to help us grow the business. We continue to reiterate our DMD revenue guidance of $285,000,000 for the full year 2019. Over the next 12 months we anticipate the launches of 4 new products which will advance our strategic objective.
Root the plan for SMA, TEGSEDI for HATTR reliever for FCS and our gene therapy product for AADC deficiency. We also have a PDUFA date for expanding Emflaza's label to include DMD patients 2 to 5 years old. In addition, there is a potential for a U. S. Approval of Translarna in 2020 based on the outcome of the dystrophin study.
The combined potential revenue and royalty streams of these products all of which are either already approved or will be submitted for approval this to in excess of To support this revenue growth, we are proud to have established a global commercial infrastructure. We are currently selling DMD therapies in over 40 countries worldwide. This is a strong commercial expertise allows us to position PTC as a key partner for collaborations and business development opportunities. Through these activities, we have strengthened our internal pipeline with the addition of Emflaza, Tegsedi, Waylivra and the CNS gene therapy platform. We plan to continue to strategically assess to patients with rare disorders In addition, we have made progress both in expanding our commercial footprint by adding an additional product to our commercial portfolio as well as in advancing our therapeutic pipeline.
We have Latin America commercial rights to TEGSEDI and Waylivra. TEGSEDI was approved last year by regulators in the United States and Europe and we are happy to report that Waylivra received a positive CFP opinion in the first quarter and we expect ratification by the European Commission Based on these approvals, we are preparing for the upcoming launches in Latin America for both products. Later this year, Analogous to how Translarna was launched in Latin America, we will be initiating early access programs ahead of formal approvals. We're encouraged by feedback from physician and patients, and we've already received requests and prescriptions. In addition, we've been working hard to advance our clinical programs.
We've been preparing for the VLA for our 1st gene therapy program in AADC deficiency this year. We are also supporting Roche for SMA NDA that will be submitted later this year. We are excited about the SMA program and as Emily mentioned, we look forward to sharing data on the SMA program next week at the AAN. Therefore we won't spend time discussing this program today. Based on the success of the SMA program, we've been utilizing the splicing platform to address other targets in rare diseases, where we believe this platform is appropriate.
We have several programs to identify other oral compounds that selectively as specifically modulates splicing. The splicing platform and subsequent programs are solely owned by PTC. We have already selected a development candidate from this platform for familial dysautonomia and plan to file an IND this year. Our research team is also working on identifying the development candidate for Huntington's disease and we anticipate this compound will enter the clinic it is a strategic priority to We have identified an approximate 100,000 Square Foot Biological Manufacturing Facility are in the process of finalizing a long term lease. The facility will allow us to use both adherent and suspension manufacturing systems in gene therapy for production and will house integrated manufacturing, analytical and quality functions.
While AADC gene therapy product will remain in production with mass biologics, for the foreseeable future, we believe control and oversight over gene therapy manufacturing will allow for the rapid development of the rest of our of our commercial and clinical progress. Marcia?
Hey, thanks. It's Tiu. We have a vision of building a portfolio of multiple products to serve patients with rare disease with the potential 20.23 revenues in excess of $1,500,000,000. Our current DMD business serves as a strong base to get us to an accelerated growth periods. And we bring several products to the markets in the coming years.
We continue to reiterate our global DMD revenue guide for this year of $285,000,000 was in line For the first quarter, we reported Translarna sales of approximately $35,000,000. As expected, this reflects a sequential decline from the fourth quarter last year due to the lumpiness of ordering patterns. Mainly from Latin America. Earlier this week, we received ANVISA regulatory approval for Translarna in Brazil. We're extremely happy to serve patients in needs.
Translarna business has grown in Brazil through early access programs. Now as a next step, We'll go through price negotiations with the Brazilian governments. This will likely result in unexpected price discounts which has potential increase in patient access in Brazil. In the U. S, our DMD business is based on Emflaza.
Which is approved for all DMD patients 5 years older. We have a PDUFA of July 4th for our application to expand the Emflaza label to include younger patients age two to five Our commercial team is diligently preparing for the potential launch in this expanded indication later this year. For the first quarter, we reported Emflaza sales of approximately $18,000,000. Prescription growth was in line with our expected 2019 guidance. However, Revenue in the quarter exclusive, a specialty pharmacy distributor.
Now moving to TEGSEDI and Waylivra. We continue to progress nicely with the tech savvy and visa review, which we expected to be concluded later this year. We are eager to bring TEGSEDI to the approximately 6000 patients in Latin America who needs it. We have now established an early access program for typesetting several countries, which should result in early adoption this year and more significant sales contribution As Stu mentioned, we are very pleased to see Waylivra has been granted a positive opinion by the EU regulators. Once this is ratified by the European Commission, we will initiate country by country early access programs in Latin America.
There are clear synergies between the patient monitoring and diagnosing teams for Tegsedi and Waylivra. We are in the final stage as mentioned by Stewart of securing our gene therapy manufacturing to support our pipeline. We remain on track to submit a PLA for AADC this year as well as an IND for Friedreich's Ataxia gene therapy later this year. We are working to identify ADC patients focusing on at risk patient population in cerebral palsy clinic. We continue to make progress and once we have screened a significant portion of these CP patients we will provide an update We're also working towards our MarTech sales strategy for AGC.
This will reflect the value seen in allowing patients to obtain never seen before, motor milestones such as sitting and walking. We look forward to bringing this life changing therapy to ADC patients worldwide in the coming year. I would now like to give a short clinical development updates, starting with Translarna. Our key dystrophin study of 45 is enrolling patients and we expect a readout early next year. Which if positive would support a resubmission to the Translarna NDA in the U.
S. For Emflaza, our limb girdle study is expected to enroll the 1st patient this quarter. Which upon completion should allow for the future label expansion. All three of our oncology trials in AML, the IPG, and LIOMiosarcoma are enrolling patients with expected expansion cohorts to be decided early next year upon initial readouts of the dose finding studies. Lastly, we're in the final stage of designing our FA trial to submit an IND.
The first for the gene therapy in this devastating disease. We expect to share details later this year. I'd now like to turn the call over to Christine, our Principal Financial Officer. Christine?
Thanks, Marcio. Earlier today, we issued a press release summarizing the details of our financial results for the first quarter of 2019 and I refer you to that release for full details. I'll start with a few comments on our financial performance and our guidance for 2019. Starting with our across our DMD franchise for the first quarter of 2019 compared to combined revenue of $56,100,000 for the first quarter of 2018. Translarna net product revenues were $35,300,000 for the quarter.
This compares to 30 6.8 is influenced by lumpy ordering patterns from Latin America. For Emflaza, we reported net product revenues of approximately $17,800,000 for the first quarter of 2019 which compares to $19,200,000 reported in the first quarter of 2018. As was mentioned, In Plaza sales were impacted in the quarter by both seasonality and a planned transition to a new specialty pharmacy. We are reiterating our 2019 DMD franchise revenue guidance of $285,000,000 to $305,000,000. We have also outlined the opportunity for pipeline to generate potential combined Non GAAP R and D expenses were $47,900,000 for the first quarter of 2019, excluding $4,700,000 in non cash stock based compensation expense compared to $27,600,000 for the first quarter of 2018, excluding $3,700,000 in non cash stock based compensation expense.
This increase in R and D expenses reflects costs associated with advancing the gene therapy platform and increased investment in research programs as well as the advancement of our clinical pipeline. Non GAAP SG and A expenses were $36,000,000 for the first quarter of 2019 excluding $4,600,000 in non cash stock based compensation expense compared to $29,000,000 in 20 18, excluding $4,000,000 in non cash stock based compensation expense, reflecting continued investment in support of our commercial activities. I would also like to reiterate our non GAAP R and D and SG and A expense guidance for full year 2019 of $3.60 to $370,000,000, excluding non cash stock based compensation expense of approximately $35,000,000. Net loss for the first quarter of 2019 was compared to a net loss Cash, cash equivalents and marketable securities totaled approximately $407,000,000 at March 31, 2019, compared to approximately $227,000,000 at December after the successful completion of a public equity offering resulted in combined net proceeds of approximately $225,000,000. We are happy to be
Thank you. You. Our first question comes from the line of Vincent Chen of Bernstein. Your question please.
Great. Thank you very much for taking the question. Apologies for the background noise. I'm at the airport on my way back from ASCCT. Was wondering if you could provide us with some insight into the level of channel inventory for Emflaza at the end of Q2.
How does compared to, I guess, sorry, the end of Q1, how does compared to the beginning of Q1 and how it compared to typical steady state levels? And then similarly to the extent that you can, could you provide us with additional color on the timing of OUS orders for Translarna in, fourth quarter 2018 first quarter 2019 and your expectations for the timing of upcoming orders
Yes. Hey, hi, Vincent. Thank you for the for the call. Marcio, why don't you hand on that one? Of course.
It's too. Hey, Vince. Thanks, thanks again for the questions. So on a question for Emflaza, right? So what I mentioned on the prepared remarks was that the part of the impacts on the quarter was in relation to the performance of our prior vendor that was handling the distribution and specialty pharmacy for Emflaza in the U.
S. And the change that we made to a new one, which we believe based on all the work that the team did, is going to be performing more in line with our expectations in terms of the supports to patients. So it's not only to your question, a matter of inventory, it's much more a matter of performance in general in terms of timing of dispense, in terms of the revenue, that's being done there. So we like we're not necessarily happy with that. So we corrected, which we believe it's it was key for the business.
But most importantly, there is no impact for the year. We have the prescriptions coming in strong in Q1. We expect this to continue to grow and to meet our year end revenue guidance. So that's what we guided for. So we remain confident on the growth short term and long term for Emflaza.
In relation to your second question on the timing of orders for Latin America, specifically for Brazil. So we had an order late Q4, which was dispensed to the patients, as you expected, now with the approval that we just received this week, from ANVISA, there are obviously more patients that are going to be having access. And just to give you a little bit of color, we haven't talked about this before, but since we were under early access programs, there are many restrictions on programs like that, including the inability of PTC to promote Translarna. So all the demand we had was spontaneous from physicians and patients and their families that medical needs, basically, but not necessarily through our active promotion. So our penetration in Brazil right now is around 25%.
What we expect to discuss more proactively Translarna that's going to substantially increase, moving forward. So we us this order later in Q4. As I mentioned, we expect 1 in Q2, based on our calculations of patients' demands that being conversations already because they are always ongoing conversations to that. And we expect the year to be, as I mentioned in the remarks as well, not to be acted by any of this in terms of the total guidance. Does that answer your questions?
Great. Thank you very much for taking the questions.
Thank you.
Comes from the line of Ritu Baral of Cowen.
Since I'm not going to ask about Risdiplam, I'm going to ask about the next best thing, I guess, which is, Stu, the Huntington's program that you mentioned. Can you walk us through, I guess, the strategy, the mechanism behind that program and, how you see the emerging landscape? There's quite a few programs, in development right now, but how do you see this fitting in?
Yes, sure. Hi, Ritu. Thanks for the question. So, the Huntington's Oh, really comes from we've it's just to remind everybody that we've built out a splicing platform where we're able to identify small molecules that selectively and specifically modulate the modulate supply seen. And in the SMA case, there was a consequence of a point mutation that made splicing less efficient in the small molecule makes it more efficient and allows the addition of the Exxon to be added where wasn't before.
It's interesting, in the case of Huntington, again, it actually alters the splicing select and specifically, but it doesn't in, I think, a quite novel way. In the case of hunting, it's a CAG repeat issue, in this case, it's almost like a pre on, right, where you get in a sense a large protein mass that ultimately causes dash of neuronal cells within the brain. And so ultimately in this case, you don't want to you want to actually reduce the level of Huntington's protein. And so what we figured out is that based on our understanding of the splicing that we have in a sense a splicing within the intron within the Huntington's gene that could be modulated by a small molecule that we've identified. And therefore, the way it works is that actually induces an Exxon to go into the Huntington's RNA that has a premature termination code on within the small Exxon, That causes a rapid degradation of the RNA and you reduce the level of protein that's been made.
And we've shown both in cells and animal models That's indeed what happens and that you actually reduce the level of the Huntington's protein as a consequence of that. So that's the strategy behind it. When you think about, what we think is a major advantage here is obviously, it's an orally bioavailable small molecule. And we think that not only as a consequence of that it will get into the regions of the brain that deep regions of the brain and often all cells so that it would actually be an effective small molecule modulator and then be able to cause the reduction of Huntington. And it's oral, so it's obviously easy.
We know how to it's easy to take. And we think obviously not only because of the mechanism as such, we think of the abroad distribution, be able to get into the all of the tissues easy to take. And therefore, it's going to be a competitive advantage as a consequence of that as well. Maybe, Marcy, you want to talk a little bit about that?
Yes, of course, Ed, hi. It's like, it's a very large market for Huntington's and for a rare disease. And is still what's saying there are a number of advantage of our approach to the others that are out there. We are learning from the others, we appreciate that there is a number of compounds in developed here, but some limitations in terms of the delivery as you just highlighted, which will, in our view, transfer to a whole body disease, just like SMA, not being able to be addressed completely. With our partnership with CITI, we actually learned a lot in terms of the other aspects.
And we continue to learn, which are very unique of this disease. And probably some subset of patients are going to be better served by some therapies than other. And we believe a neural molecule is going to have like a prominence position in the marketplace. So we feel extremely excited when we want to enter the clinic next year as guided previously and we're on track to do that.
Can you just reduce the normal Huntington protein as well as the mutant Huntington protein or just mutant?
No, so yes, so this molecule does both. The normal and mutant. And so the I think the common thinking within the community is if you could reduce it by 5th percent or so. That's what we're targeting to reduce the mutant hunting to protein. It's just still enough normal Huntington's protein that we don't think would be an issue.
Got it. And quick follow-up. Marcio, could you walk us through what the strategy, your current strategy is for the Translarna resubmission for the FDA At the beginning, you had noted that there were a couple different, data cuts biopsy data cuts that could fuel a resubmission, but what have you settled on looking at early data?
Absolutely happy to. So the key trial for the resubmission early next year is Study45. And basically, what that study is, We're doing a needle biopsy. So we're taking 4 cores in this biopsies. It's about 150 to 100 milligrams of muscle.
We're doing 2 types of quantification of dystrophin with methodologies that we've validated and agree with the FDA that would be adequate. So we're enrolling that study. It's a single site to reduce variability in California, like we're very happy with how the quality of the biopsies are coming. We obviously don't do the quantification early on, but we like check for quality in terms of infiltration and so on. And so they're coming as we expected in terms of that.
And the enrollment is being quite nice. So it's taking the pace that we expected for these readouts early next year. The duration of treatments, once the patient started and had the baseline biopsies 9 months. The way we decided to do in agreement with the FDA, since there is no control group, we're going to be batching all the samples together and all of them are going to be read at the same time point at the end of the study. So there's not going to be a readout in between or anything like that.
For this study. So this is our primary study. It's the one that we have agreed to. We are running another study as we mentioned before as well. Exploratory in terms of understanding like the levels of expression in patients who were previously exposed.
Translarna, we call that 3046. That study is up and running as well, and we are seeing some very good interest in enrolling And for that, it's a little bit more liberal inclusion. There is no baseline. So really looking into trends and in terms of our own understanding of long term ration, but that's going to be complementary and a supplement to Study 45 for the resubmission, not the key study at this point in time.
Got it. Thanks for taking all the questions. Thank you.
Thank you. Our next question comes from Eric Joseph of JP Morgan. Your question please.
Hey guys, afternoon. Thanks for taking the questions. Just a couple commercial and one development. I guess first on Translarna, Marcio, would you be able to, kind of orient us around the amount of discounting that you're debating as a result of negotiations, in that country and whether that pricing would serve as, I guess, reference pricing in the broader region. And on Emflaza, I'm just wondering if you can kind of help us kind of understand And just in thinking about the push pull drivers here, what you're seeing in terms of patient adherence of late end, what your expectations are on, net price going forward?
Yes. No, of course. And thanks, Eric, for the questions. So on the pricing in Brazil for Translarna and I would say there are 2 tiers here. So the first one at the time of the approval, new orders have a mandatory rebate.
So let's think about this like our CMS, right, rebates in the United States, actually about of the same magnitudes of 20% And that's why we call that's why we call CAP there or CAP, and that's going to be applied to our orders moving forward. We submitted price requests to the body in the Brazilian government called CMEDs, the regulated price, We didn't hear back from them yet. And based on that, that's where the actual price negotiation is going to be done, which we feel very confident is going to be within happened in the past like few percent more than demand of our discounts. This is all included in our guidance for this year. Right?
And it's the magnitude of the discount is much smaller than the expectation that we have to grow the markets. So it's a net positive ballpark 2019. But most importantly, for the future, as I mentioned before on the previous question from Vincent, is, we only have 25% penetration there, which is quite impressive when you compare with others early access programs, but it's relatively small for the potential of the markets. So we expect to get a substantial number of page increasing in terms of treatment on the following years. For the Emflaza question, that you asked.
So the dynamics, and again, there's a number of levers here, that we have to account for, right? So the number of new prescriptions are exactly as we expected. We're having good traction there. We mentioned late last year, we'll end in the bridge program. We did that.
A portion of those patients was transitioned and we're having good traction there as well. There's a fewer number of patients in free drug that we continue to transition to compliance, and this drug is being pretty high for our neuro that is taking daily, but not anything like Translarna which we have like 95% or so. It's more in line with other oral drugs in that regard. But we are not seeing any dynamic that is negative to the market. If anything, all the dynamics we are keeping are tracking are positive.
One thing I mentioned as previous call is that we're going to expand the sales force, because we believe there were some areas that required more education and we did that with the exercise, we completed the hiring and they are all in the field and we should see the benefits of that expansion later in the year as well.
Got it. Maybe just one development, if I could. I want to try and look past A and to cure at I may. And just wondering if you could, are you just around Juulfish where you guys will be presenting, just how to think about patient numbers, duration of follow-up. I understand that it's primarily a PD and safety trial, but I'm also curious to know whether we should be, whether there'll be measures of functional benefit as part of that follow-up, the patient follow-up there?
Yes. So I think, hi, Eric. So I think, obviously, we're including other patients in gene therapy and they'll be discussing at Cure SMA think there's going to be a lot of data that's early at that time, but you'll see some, that there'll be some increments of other things as well. But I don't think yet we're going to have a lot of data for this.
Got it. That's helpful. Thanks for taking the questions, guys.
Thank you.
Thank you. Our next question comes from Gena Wang of Barclays. Your line is open.
Thank you for taking my questions. And I apologize. I joined the call a bit late and it's already discussed. I apologize. So I also have 2 commercial questions regarding Translarna and Vazlava.
For Translarna, can you remind us the Brazil sales in 2018 and how's the pattern look like
Sure. Hey, Jean, and no worries at all. Happy to address any questions. So, we haven't guided for country or region specific revenues in the past. It's pretty obvious by the variation that we have when we have a large order from Brazil.
That's a substantial business for the of the count 3 and the number of patients we have, we haven't given, exact numbers. But we have
Maybe it's good to talk about. Even we a bit about like Germany and others where we saw.
Yes. So it's a growing market. It's fairly substantial. We had a number of patients that have been found. It's one of the most successful patient finding exercise we have going on globally.
So as Stu has mentioned, it's bigger than some of the more established markets in Europe. And it's going to continue to go in that direction. Well, there's than 300,000,000 people there. So I think it's, easy to see how it can continue to grow. So we see the patents for, for Translarna there as enforceable.
Obviously, we take very seriously our IP this being discussed and being submitted together with our regulatory submission, we don't see any percent. I know there are cases recently, unilateral decisions, other types of issues from the governments, in Brazil that that might be creating our question, but we don't see that kind of risk at this point in time. For Translarna, our relationship and our level of collaboration with the markets in general key opinion leaders and the government has been very friendly, differently from some of the other circumstance that happen. But we feel very strongly, it's a very long runway there, beyond the planning period that we've been talking about.
Thank you. And I have another question regarding Emflaza. So just wondering if you can provide a color, the breakdown of patient had a prior premise on treatment versus the prior deflexicort treatment? And then how does the tram look like? In this quarter versus the last few quarters?
Oh, that's a great question. And thank you so for that. So less the last 18 months or so, we've been focusing a lot on getting these patients who are previously had some exposure to deflazacore, like Emflaza, as I mentioned. And like secondarily changing, they strategy to focus on the expansion with prednisone. There are step edits in most plans, as you know, for prednisone before treatment, which Plaza.
Some of them, very recently had been removed or reduced. So we are happy with that. What we are seeing now And I would say mostly on the last 90 days, 120 days or so is a big trends and change towards patients switching therapy con on call. So patients who were originally on prednisone been using that for a while that are choosing actively to use Emflaza, which is ultimately what we want the entire markets to turn to, right? This, we believe and so does the key opinion leaders is a better alternative for the patients and we can continue to communicate that and to engage in dialogues for the patients to switch.
So moving forward, the entire year growth is basically predicated on prednisone and to a secondary degree on new patients on therapy since this market is still growing and there's a substantial number of patients who are not on treatment with any steroids right now. So kind of chew buckets to get patients from.
And we've been able because of the publications that came out last year, not only on our own data, but also on the natural history that really gave us a lot of a lot of material to be able to go to the payers, but then so that we can then where we can use those to demonstrate the end plazas, better efficacy. So that's helped quite a bit as well. That's also why people I think we're seeing the bigger changes over time.
Just wondering what is the percentage of patient like a non ambulatory patient that on drug right now?
Flaza, I assume, right? So it is not a disproportional with how the market is. That the basically if you look into the last 10, 15 years, right, how steroids treatment changed was almost 6 exclusively for ambulatory patients. And just recently, physicians became more comfortable and the evidence became more clear that non ambulatory patients should be treated. So we got a lot of new requests for non ambulatory as well.
We have a substantial number of patients But it's still not what you would expect to be that is almost fifty-fifty. It is still more disproportional, I would say, towards ambulatory at this point in time. And younger patients coming in as well, a lot of excitements in terms of the expansion of the label to 225 which is going to capitalize the growth as well later this year.
Again, the papers are helping a lot because of the natural history showing better lung function of patients are on Emflaza.
Thank you very much.
Thanks, John. Thank
you. Our next question comes from the line of Roger Prasad of William Blair. Your question please.
Thanks for taking the question. Marshall, I think you previously mentioned hiring all the self the expanded sales force in Latin America. Can you just put some metrics around the number of reps that you've hired? And then with several recent approval in Latin America, just approximately what percent of your kind of $1,500,000,000 in 2023 will be coming from Latin America versus EU versus U. S?
Thanks.
Oh, sure. Hey, Raj. So, like the first question, right? So the expansion, we expanded both in the U. S.
For Emflaza and that was about 20% increase on the number of sales force. And we also increased the the size of collaboration Latin America in general, not only in Brazil, but in Colombia and Argentina, as we have like our main operations as well. The numbers are fairly small in absolutes. So it would be somewhat silly for me to actually say like percent. So we at like 3 or 4, more individuals here and there.
So in absolute, there's relatively small, but for coverage of the country makes, make a lot of sense. So we believe we have a very good coverage right now, like we have very focused efforts on neurologists and pediatricians, to cover both products, since you know, dramatically have both actively now TEGSEDI and Lerna and starting to introduce Waylivra as well, which you're going to have a small expansion to cover the additional properties that are covered by Waylivra. When you look into the 2023 guidance, the biggest contributor there coming from Latin American General, it's TEGSEDI. We talked about $150,000,000 at that point in time. We still feel very confident about that and about the early indicators that we are seeing in terms of demands that is coming from all the markets.
And for the other products as a lesser, it's a little bit more, balance, I would say, part of the business. We haven't guided regionally. So, I don't think it would be appropriate for us to do this right now, but it's still an important market us, but it's not the predominant markets, moving forward. If you look into the U. S, for example, for Translarna, 2023.
We're talking about $200,000,000, which arguably has a lot of potential to grow from that number as well. So we again, our approach for guidance is really to make sure we deliver on that and we continue to look into these metrics we're feeling very good about it.
Thank you. Our next question comes from Tazeen Ahmad of Bank of America. Your line is open.
So, Marcia, just wanted to
get your thoughts about WAYLIVRA and TEGSEDI. This could be something that might be underappreciated on the Street. How are you thinking about the market opportunities in LatAm? You've obviously done some work on this. You've started to initiate the early access programs.
As we try to think about value in the models for these contributors, how do you think the best way of guiding us would be? Thanks. Then I have a follow-up.
Of course. Hey, Tazeen. Good to hear from you. So I completely agree with your assessments. I think we've been saying this, right?
And we are seeing they realize. So let me start with Waylivra first. Even like before the approval or the better, the recommendation from CHMP for the European Commission to approve we've seen a lot of demands from patients. Somewhat's even more than we were expecting in terms of the awareness. Of FCS in the region.
So we are seeing a substantial number of cardiologists and other specialty coming up to us and saying like I have a family, I have a number of patients here, even with little work that was done since we're gated completely in terms of investment and efforts before the recommendation. So we believe that the Waylivra opportunities in the region is going to be as big as Translarna. And we haven't guided regionally, but you would impact that is fairly substantial, right, anywhere in terms of like 500 patients to even potentially more since our early reads in the prevalence and the incidence of that seems to be actually on the higher ends, not on the lower ends, of the range. So excited about the product, excited with the potential for revenue in all the key markets there and having some goods early, like we have spontaneous demand for Waylivra right now, meaning physicians are prescribing, we're becoming aware of this coming through the channel. It takes a while to materialize as revenue, but it's happening.
In terms of TEGSEDI, I would say all the systems are green and everything is gold. The monitoring programs in place, feedback from the pay that we consulted physicians being excellent in terms of what they're getting from PTC and our exclusive partner there. The number of patients that was coming through our genotyping programs quite impressive as well on top of the ones that are already identified. Different I because in Brazil alone, we were talking about around 4800 patients, given taken for, the HHS So it's much bigger for 6000 patients expected in Latin America. So our somewhat I would say, realistic guidance, as I mentioned on Raj, question is $150,000,000 for TEGSEDI within into 2023.
We didn't give guidance for delivery yet, but you would expect it's, that that's going to be substantial. So I appreciate interest on that and the opportunity to talk a little bit more about these 2 assets. And you said you had a follow on.
Yes, if you could, just for Translarna to talk about the European opportunity. I think in March, you announced that you had as it relates to Study 041 asked the EMA, for an extension of when you were able to submit that data. I think originally plan was to submit that data for the end of the maybe third quarter of 2021, but that's due to slower pace of enrollments. You've for 1 year extension on that. So I just wanted to get a sense from you as to why you think that enrollment might be slower than might initially have anticipated.
Yes. Maybe go ahead, Michael.
Of course, too. So, O41 in a sense, the enrollment for the study is a little tricky, right? Because it is a placebo controlled study and we are fairly successful on the markets in Europe and Latin America, for example, So there's not a lot of patients available on these core markets for enrollments. So we had to expand this to other countries like in Asia, some countries in Latin America, we are not commercially the United States. So originally, some of those countries took a little bit longer to open the sites.
And while the patients are there, and we're like very confident enrollment is going as expected now as we communicated to DMA it was as lower to start. So it was not an interest or even availability of patients. It was more starting up the site environment for some of them. And to be honest, some of the, countries in Europe like that, we are not present in Eastern Europe. For example, they simply didn't want to start the study because they were anticipating, getting commercial Translarna during the study conducts.
So all those factors with being informed mediaMA was not simply a submission to them and like, Hey, we want 1 more year here. We've been in contact with them. We've been informing of the progress and we formally requested an extension during the renewal procedure this year. Based on the communications we had with them before the submission and interactions, we don't believe that's going to be an issue. We believe that one year is going to be plenty for us in terms of the extension.
And we feel that it's going the right direction in the last few months with all the sites opened it picked up quite a bit and it put us in definitely not comfortable situation.
Thank you. Our next question comes from the line of Brian Abrahams of RBC Capital Markets.
Hi. This is Bert on for Brian. Thanks for taking our question. I just wonder if you could speak a little bit more on building out gene therapy manufacturing capabilities in house. I know you mentioned earlier that the new facility would have both adherent and suspension capabilities.
But, is there any more like established gene therapy manufacturing program that you're kind of using guide or learning from? And are there any kind of timelines or milestones for this process that that we could look for?
Obviously, when we picked our CNS gene theory programs, we were I think we thought we were pretty thoughtful from the notion of that since since you're injecting directly into the region that the levels of the material that would be needed are less, for example, the case of what we're doing for ADC deficiency, it's like 2 times 10 to 11 and their total. So it's like per kilogram, it's just total amounts there. And so that gives us the opportunity to be able to manufacture, but at a level that we think is really quite doable. Right now, we're going to we're not that is not meant for the facility that we'll be going into. That's going to be done by MassBio, which we've been working on that with them.
And that's going to be our commercial CMO for that. So they'll be making it for the foreseeable future. In terms of the manufacturing, of the facility that we have that we'll be going into, we think that facility is going to be it's obviously going to be committed to gene therapy. The it is an existing biologics facility. And it's an operating plant that will be designed obviously for GMP standards.
So we'll have to make some modifications for the gene therapy and we'll adapt it to that. Otherwise, I think we'll be moving in and continue to work on. Obviously, we have a set of other programs that we're doing that includes Friedreich ataxia. Angel means and others that will be going. Then we'll be moving in and we've started to obviously hire really qualified people who have expertise and experience.
This region that will help get us going within that plant. And so I think that's think we're in actually pretty good shape to get that ready and go.
Great. Thank you.
Our next question comes from the line of Alethia Young of Cantor Fitzgerald. Your line is open.
Hi. This is Irene on for Alicia. Thanks so much for taking the question. So just one on AADC, can you give us an update on where you stand with the filing preparations for that? And what the remaining steps on the manufacturing front for that program are?
Thanks.
Yes, sure. I think we're in terms of the manufacturing of this or where we are is obviously we have the results that we've talked about over here for quite some time. And we think they're really, pretty incredible results in demonstrating the ability of kids to go in a sense, you've seen the number of them who were basically placid children that were capable of walking that all the kids were able to improve. Really now we're just completing the CMC part of that. And that's really just, doing the comparability studies to get it all completed the file by the end of the year.
And so what we're iterating now that we think we're on track for that to to be able to complete that. So the BLA for ADC will be submitted by the end of the year. So in we feel good that everything's on track including the manufacturing, to allow us for the BLA.
Thank you.
Thank you. Our next question comes from the line of Joel Beatty of Citi. Your line is open.
Hi, thanks for taking the questions. The first one, a follow-up on the AADC program and manufacturing Could you discuss the steps that you need to take to give FDA confidence that manufactured gene therapy will be comparable to what was used in the clinical trials?
Sure. Yes, Marcio, I want to actually.
Of course, hey, Joe, how are you? So basically the process that we used before in the 2 other sites that produce the material are essentially the same, right? So we are using adherence, ATK293 here in hyper stacks. That was what is used before. Obviously, that was done in a clinical level.
We are looking now into commercial. So there was like a number of conversations we had with the FDA in terms of what they expect for that, what's the product comparability, like we're not changing process per set. So we are looking into the previous drug analytically been comparable to. So the 2 key steps here, I would say missing, there's obviously a number of things that are being done, but the 2 is one is analytical methods to commercial grades release specs that we discussed with the FDA being finalize and testing the batch we've been producing, getting the release batch or we call PPQ1 as you are probably very familiar with. Getting the PPQ1 released using those methods, using the data that we collected to getting the certificate of analysis for that batch to include on the BLA.
Everything we've been doing so far, every step I don't know how NIO still has a little bit doesn't have a little bit of time because it's been running around and making sure everything is absolutely on and absolutely perfect with his team, but they're working very hard. They are doing like a great job on getting every step of the way either on time or if ahead of time so we can file the BLA because these patients really need this. So everything so far so good We take this very seriously. We want to make sure the product has the product is the quality, in terms of biologics. We're doing everything we can to get the kind of product we need for those patients.
Considering the level of inventories as well, that we believe are going to be adequate for a successful launch. Since we are identifying patients every single day with agency and we are driving for a successful launch, we are matched not only the manufacturer in terms of the specs, but making sure we have adequate levels of support for a successful launch in the United States and subsequently globally.
And again, the big picture here is that you didn't change the process from clinical to commercial. So there wasn't in terms of comparability, it's really just saying you have the same materials from the same way you made it. But help us transfer of protocol rather than a different way of doing it. So we feel pretty good that we'll be able to complete this and get the BLA in by the end of the year.
Got it. And thanks for that. And then a clarification question on Translarna revenues that were down quarter compared to the first quarter of 2018. But is that driven by volumes or is there a pricing component there?
Yes. No, there's no pricing components there. That's mostly some orders like in Q4 that came like 4Q for Q1 and some timing of orders in Q1 as well. And new patients we're getting are younger So the like average price per patient is a little bit lower as well. So it's more a mix, I would say, than the absolute price of the drug.
We've been able to keep a pretty good stable international price.
Great. Thank you.
Thank you.
Thank you. At this time, I'd like to turn the call back over to our CEO, Stuart Peltz for closing remarks. Sir,
Thank you. The remainder of 2019 brings some major milestones for us. And this includes submitting the 1st gene therapy BLA for AADC deficiency, the SMA NDA by Roche, and the launch of the TEGSEDI and Reliever in Latin America that we've been discussing. We are following through on our vision of building a fully integrated Biotech Company addressing rare disorders worldwide. We look forward to sharing the progress of the Risdiplam for SMA at a/nd next week.
And I thank you for joining the call today.
Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day. You may disconnect your lines at this time.