Good day, ladies and gentlemen. Thank you for your patience. You've joined PTC Therapeutics 2019 first quarter corporate updates and financial results call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session. Instructions will be given at that time. Should you require any additional assistance during the call, please press star then zero on your touchtone telephone. 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. 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, our Principal Financial Officer, Christine Utter. 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 our slide on our simultaneous presentation, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements. Any and such risks can materially and adversely affect our business and results of operation. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q and annual report on 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 for today's earnings release. Before I hand the call over, I would like to point out that given that 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 million-$305 million for the full year 2019. Over the next 12 months, we anticipate the launches of four new products which will advance our strategic objective.
Risdiplam for SMA, Tegsedi for hATTR, Waylivra 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 year, is anticipated to grow to in excess of $1.5 billion in potential revenues by 2023. 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 external opportunities to grow our business and bring differentiated treatments 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 CHMP opinion in the first quarter, and we expect ratification by the European Commission in the coming days. 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 have already received requests and prescriptions. In addition, we've been working hard to advance our clinical programs. We have been preparing for the BLA for our first 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 have 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 and specifically modulate 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 a development candidate for Huntington's disease, and we anticipate this compound will enter the clinic next year.
As we discussed on our last call, it is a strategic priority to bring gene therapy manufacturing in-house to support our gene therapy pipeline. We have identified an approximate 100,000 sq ft biological manufacturing facility and 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 MassBiologics for the foreseeable future, we believe control and oversight over gene therapy manufacturing will allow for the rapid development of the rest of our pipeline. I'll now turn the call to our COO, Marcio Souza, to discuss details of our commercial and clinical progress. Marcio?
Hey, thanks, Stu. We have a vision of building a portfolio of multiple products to serve patients with rare diseases, with the potential 2023 revenues in excess of $1.5 billion. Our current DMD business serves as a strong base to get us to an accelerated growth periods and will bring several products to the market in the coming years. We continue to reiterate our global DMD revenue guidance for this year of $285 million-$305 million.
Our first quarter performance was in line with our expectations. Our DMD franchise includes Translarna outside of the U.S. and Emflaza in the U.S. For the first quarter, we reported Translarna sales of approximately $35 million. 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 for this additional validation of the benefit risk of Translarna to serve patients in need. For the most part of the last four years, Translarna business has grown in Brazil through early access programs. As a next step, we'll go through price negotiations with the Brazilian government. This will likely result in an expected price discount, which has been reflected in our original guidance. Over time, the Anvisa approval will allow for a substantial increase in patient access in Brazil. In the U.S., our DMD business is based on Emflaza, which is approved for all DMD patients five years and older. We have a PDUFA of July 4th for our application to expand the Emflaza label to include younger patients age two to five.
For the first quarter, we reported Emflaza sales of approximately $18 million. Prescription growth was in line with our expected 2019 guidance. However, revenue in the quarter was impacted by both seasonality and a planned transition to a new exclusive specialist pharmacy distributor. Moving to Tegsedi and Waylivra. We continue to progress nicely with the Tegsedi Anvisa review, which we expect to be concluded later this year. We're eager to bring Tegsedi to the approximately 6,000 patients in Latin America who needs it. We have now established an early access program for Tegsedi in several countries, which should result in early adoption this year and more significant sales contribution next year. 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 Stu, of securing our gene therapy manufacturing to support our pipeline. We remain on track to submit a BLA for AADC this year, as well as an IND for Friedreich's Ataxia gene therapy later this year. We are working to identify AADC patients, focusing on at-risk patient population in cerebral palsy clinics. We continue to make progress, and once we have screened a significant portion of these CP patients, we will provide an update on the expected patient numbers for launch. We're also working towards our market access strategy for AADC.
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 AADC patients worldwide in the coming year. I would now like to give a short clinical development update, starting with Translarna. Our key dystrophin study, Study 045, 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 first patient this quarter, which upon completion should allow for the future label expansion. All three of our oncology trials in AML, DIPG, and leiomyosarcoma 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 would 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 top-line results, we reported $53.1 million in combined net revenue across our DMD franchise for the first quarter of 2019, compared to combined revenue of $56.1 million for the first quarter of 2018. Translarna net product revenues were $35.3 million for the quarter. This compares to $36.8 million in the first quarter of 2018. As Marcio mentioned, our Translarna revenue trajectory is influenced by lumpy ordering patterns from Latin America.
For EMFLAZA, we reported net product revenues of approximately $17.8 million for the first quarter of 2019, which compares to $19.2 million reported in the first quarter of 2018. As was mentioned, EMFLAZA 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 million-$305 million. We have also outlined the opportunity for our pipeline to generate potential combined revenue in excess of $1.5 billion by 2023.
Non-GAAP R&D expenses were $47.9 million for the first quarter of 2019, excluding $4.7 million in non-cash stock-based compensation expense, compared to $27.6 million for the first quarter of 2018, excluding $3.7 million in non-cash stock-based compensation expense. This increase in R&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&A expenses were $36 million for the first quarter of 2019, excluding $4.6 million in non-cash stock-based compensation expense, compared to $29 million in 2018, excluding $4 million 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&D and SG&A expense guidance for full year 2019 of $360 million-$370 million, excluding non-cash stock-based compensation expense of approximately $35 million. Net loss for the first quarter of 2019 was $72.1 million, compared to a net loss of $19.3 million for the first quarter of 2018. Cash, cash equivalents, and marketable securities totaled approximately $407 million at March 31st, 2019, compared to approximately $227 million at December 31st, 2018. After the successful completion of a public equity offering resulted in combined net proceeds of approximately $225 million. We are happy to be in a strong financial position to advance our programs and grow our business. I will now hand the call over to the operator to start our question and answer session. Operator?
Thank you. Ladies and gentlemen, to ask a question, press star one on your touch-tone telephone. Again, that's star one on your touch-tone telephone to ask a question. If your question has been answered or you wish to remove yourself from the question queue, press the pound key. Again, that's star one on your touch-tone telephone to ask a question. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from the line of Vincent Shen of Bernstein. Your question please.
Hey, thank you very much for taking the question, and apologies for the background noise. I am at the airport on my way back from ASTCT. I was wondering if you could provide us with some insight into the level of channel inventory for EMFLAZA at the end of Q2, how this compared to the end of Q1, how this compared to the beginning of Q1, and how it compared to typical steady state levels. Similarly, to the extent that you can, could you provide us with some 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?
Yeah. Hey. Hi, Vincent. Thank you for the call. Marcio, why don't you handle that one?
Of course. Stu, hey, Vincent. Thanks again for the question. On the question for EMFLAZA, right? 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 special pharmacy for EMFLAZA in the U.S. 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. 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.
We're not necessarily happy with that, so we corrected, which we believe it was key for the business. 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. That's what we guided for. 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.
Just to give you a little bit of color, we haven't talked about this before, but since we were under early access program, there are many restrictions on programs like that, including the inability of PTC to promote Translarna. All the demand we had was spontaneous from physicians and patients and their families through medical needs, basically, but not necessarily through our active promotion. Our penetration in Brazil right now is around 25%. What we expect is that moving forward with the approval, and therefore our fields team and our medical team being able to discuss more proactively Translarna, that's going to substantially increase moving forward. We got this order late Q4, as I mentioned. We expect one in Q2, based on our calculations of patients' demands. There've been conversations already because these are always ongoing conversations to that.
We expect the year to be, as I mentioned in the remarks as well, not to be impacted by any of this in terms of the total guidance. Does that answer your question?
Great. Thank you very much for taking the questions.
Thank you.
Thank you. Our next question comes from the line of Ritu Baral of Cowen. Your line is open.
Hi, guys. Thanks for taking the question. Since I'm not gonna ask about risdiplam, I'm gonna 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?
Yeah, sure. Hi, Ritu. Thanks for the question. The Huntington's really comes from, 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 splicing. In the SMA case, it was a consequence of a point mutation that made splicing less efficient, and the small molecule makes it more efficient and allows the addition of the exon to be added where it wasn't before. It's interesting, in the case of Huntington, again, it actually alters the splicing selectively and specifically, but it does it in, I think, a quite novel way. In the case of Huntington, it's a CAG repeat issue, in this case, it's almost like a prion, where you get, in a sense, a large protein mass that ultimately causes death of neuronal cells within the brain.
Ultimately, in this case, you want to actually reduce the level of Huntington's protein. 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. The way it works is it actually induces an exon to go into the Huntington's RNA that has a premature termination codon within the small exon. That causes a rapid degradation of the RNA, and you reduce the level of protein that's been made. 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. 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. 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, then be able to cause the reduction of Huntington. It's oral, so it's obviously easy. It's easy to take, and we think, obviously, not only because the mechanism is such, we think it'll be a broad distribution, be able to get into all of the tissues, easy to take, and therefore, it's going to be a competitive advantage as a consequence of that as well. In terms of the market, maybe Marcio, you want to talk a little bit about that?
Yeah, of course, Ritu. Hi, it's a very large market, Huntington's, for a rare disease. As Stu was 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 being developed here. Some limitations in terms of the delivery, as you Stu 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 CFTI, we actually learn a lot in terms of the other aspects. 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. We believe an oral molecule is going to have a prominent position in the marketplace.
We feel extremely excited, we want to enter the clinic next year as we guided previously, we're on track to do that.
Do you reduce the normal Huntington protein as well as the mutant Huntington protein, or just the mutant?
No. Yeah. This molecule does both the normal and mutant. I think the common thinking within the community is if you could reduce it by 50% or so, that's what we're targeting to reduce the mutant Huntington's protein. Yet there's still enough normal Huntington's protein that we don't think it would be an issue.
Got it. A quick follow-up. Marcio, could you walk us through what your current strategy is for the Translarna resubmission to the FDA? At the beginning, you had noted that there were a couple different biopsy data cuts that could fuel a resubmission, what have you settled on looking at early data?
Absolutely, happy to. The key trial for the resubmission early next year is Study 45. Basically, what that study is, we're doing a needle biopsy, we're taking four cores in this biopsy. It's about 150 to 200 milligrams of muscle. We're doing 2 types of quantification of dystrophin with methodologies that we validated and agree with the FDA that would be adequate. We're enrolling that study. It's a single site to reduce variability in California. We're very happy with how the quality of the biopsies are coming. We obviously don't do the quantification early on, we check for quality in terms of infiltration and so on. They're coming as we expected in terms of that, and enrollment is being quite nice. It's taking the pace that we expected for these readouts early next year.
The duration of treatment, once the patient started and had the baseline biopsy, is nine 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, all of them are going to be read at the same time point at the end of the study. There's not going to be a readout in between or anything like that for this study. This is our primary study, is the one that we have agreed to. We are running another study, as we mentioned before as well, exploratory in terms of understanding the levels of expression in patients who were previously exposed to Translarna. We call that Study 46. That study is up and running as well, we are seeing some very good interest in enrolling.
For that, it's a little bit more liberal. The inclusion, there is no baseline, so really looking into trends and in terms of our own understanding of long-term expression. 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 JPMorgan . Your question, please.
Hey, guys. Good 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 anticipating as a result of negotiations in that country, and whether that pricing would serve as, I guess, reference pricing in the broader region? On EMFLAZA, I'm just wondering if you can help us understand, just in thinking about the push-pull drivers here, what you're seeing in terms of patient adherence of late and what your expectations are on net price going forward.
Yeah, no, of course. Thanks, Eric, for the questions. On the pricing in Brazil for Translarna, I would say there are two tiers here. The first one, at the time of the approval, new orders have a mandatory rebate. Let's think about this like our CMS rebates in the U.S. Actually about of the same magnitudes of 20%, and that's what we call CAP there, or CAP, and that's going to be applied to all orders moving forwards. We submitted price requests to the body in the Brazilian government, it's called CMED, that regulates price. We didn't hear back from them yet. Based on that's where the actual price negotiation is going to be done, which we feel very confident is going to be within happens in the past, like few percents more than the mandatory discounts.
This is all included in our guidance for this year, right? It's the magnitude of the discount is much smaller than the expectation that we have to grow the markets. It's a net positive both for 2019, but most importantly for the future, as I mentioned before in 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. We expect to get a substantial number of patients increasing in terms of treatment on the following years. For the EMFLAZA question that you asked, the dynamics, again, there's a number of levers here that we have to account for, right? The number of new prescriptions are exactly as we expected. We're having good traction there.
We mentioned late last year we're ending the bridge program. We did that. A portion of those patients was transitioned, we're having good traction there as well. There's still a number of patients in free drug that we continue to transition to. Compliance in this drug is being pretty high for an oral that is taken 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. We're not seeing any dynamic that is negative to the market. If anything, all the dynamics we are keeping, tracking are positive. One thing I mentioned as well previous call is that we're going to expand the sales force, because we believe there were some areas that required more dedication. We did that. We completed 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.
Of course.
I want to try and look past AAN to Cure SMA, and just wondering if you could orient us around JEWELFISH, 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 there'll be measures of functional benefit as part of that patient follow-up there.
Yeah. Hi, Eric. I think, obviously we're including other patients in gene therapy, and they'll be discussed in at Cure SMA. I don't think there's going to be a lot of data necessarily at that time, but you'll see there'll be some increments of other things as well. 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 question, guys.
Thank you.
Thank you. Our next question comes from Gena Wang of Barclays. Your line is open.
Thank you for taking my questions, I apologize I joined the call a little late and it's already discussed. I apologize. I also have two commercial questions regarding Translarna and EMFLAZA. For Translarna, can you remind us the Brazil sales in 2018 and how the pattern look like?
Sure. Hey, Gena, no worries at all. Happy to address any question. 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 is a substantial business for the size of the country 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 talked a bit about Germany and others where-
Yeah
we saw.
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 exercises we have going on globally. As Stu was mentioning, it's bigger than some of the more established markets in Europe, and it's going to continue to go in that direction. There's more than 300 million people there. I think it's easy to see how it can continue to grow. We see the patents for Translarna there as enforceable. Obviously, we take very seriously our IP that's being discussed and being submitted together with our regulatory submission. We don't see any threat per se. I know there were cases recently, unilateral decisions, other types of issues from the governments in Brazil that might be creating a question.
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 in the government, has been very friendly, differently from some of the other circumstances that happened. We feel very strongly it's a very long runway there beyond the planning period that we've been talking about.
Thank you. I have another question regarding EMFLAZA. Just wondering if you can provide a color, the breakdown of patient had a prior prednisone treatment versus the prior deflazacort treatment, and then how the trend looks like-
Yeah
in this quarter versus the last few quarters.
The last 18 months or so, we've been focusing a lot on getting these patients who previously had some exposure to deflazacort, like EMFLAZA, as I mentioned, and secondarily, changing their strategy to focus on the expansion with prednisone. There are step edits in most plans, as you know, for prednisone before treatment with EMFLAZA. Some of them very recently have been removed or reduced, so we're 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 trend and change towards patients switching therapy, quote, unquote. 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 market to turn to, right?
We believe, and so does the key opinion leaders, is a better alternative for the patients, and we continue to communicate that and to engage in dialogues for the patients to switch. 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. Two buckets to get patients from.
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 material to be able to go to the payers, where we can use those to demonstrate the EMFLAZA's better efficacy. That's helped quite a bit as well, and 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?
On Emflaza, I assume, right? Is the question.
Emflaza. Yes.
Yeah.
Yes.
It is not a disproportional with how the market is. Basically, if you look into the last 10, 15 years, right, how steroids treatment changed was almost exclusively for ambulatory patients. Just recently, physicians became more comfortable and the evidence became more clear that non-ambulatory patients should be treated. We get a lot of new requests for non-ambulatory as well. We have a substantial number of patients, but it is still not what you would expect to be that is almost 50/50. It is still more disproportional, I would say, towards ambulatory at this point in time. Younger patients coming in as well, a lot of excitement in terms of the expansion of the label to two to five, which is going to catalyze the growth as well later this year.
Again, the papers are helping a lot because of the natural history showing better lung function if patients are on Emflaza.
Thank you very much.
Thanks, Gena.
Thank you. Our next question comes from the line of Raju Prasad of William Blair. Your question please.
Thanks for taking the question. Marcio, I think you previously mentioned hiring all 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 approvals in Latin America, just approximately what % of your $1.5 billion in 2023 will be coming from Latin America versus EU versus U.S.? Thanks.
Oh, sure. Hey, Raju. The first question, right? The expansion, we expanded both in the U.S. for EMFLAZA, and that was about 20% increase on the number of sales force. We also increased the size of coverage in Latin America in general, not only in Brazil, but in Colombia and Argentina, as we have our main operations as well. The numbers are fairly small in absolutes, it would be somewhat silly for me to actually say %. We add three or four more individuals here and there. In absolute, there's relatively small, but for a coverage of the country, makes a lot of sense. We believe we have a very good coverage right now. We have very focused efforts on neurologists and pediatricians to cover both products.
Since in Latin America, we have both actively now Tegsedi and Translarna, and starting to introduce Waylivra as well, which is going to have a small expansion to cover the additional specialties that are covered by Waylivra. When you look into the 2023 guidance, the biggest contributor there coming from Latin America in general is Tegsedi. We talked about $150 million at that point in time. We still feel very confident about that and about the early indicators that we're seeing in terms of demands that is coming from all the markets. For the other products, it's a little bit more balanced, I would say, part of the business. We haven't guided regionally, I don't think it would be appropriate for us to do this right now. It is still an important market for us, but it's not the predominant markets moving forward.
If you look into the U.S., for example, for Translarna in 2023, we're talking about $200 million, which arguably has a lot of potential to grow from that number as well. Again, our approach for guidance is really to make sure we deliver on that and we continue to look into these metrics, and we're feeling very good about it.
Great. Thank you.
Thank you.
Thank you. Our next question comes from Tazeen Ahmad of Bank of America. Your line is open.
Hi, good afternoon. Thanks for taking my questions. Marcio, I 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. I completely agree with your assessments. I think we've been saying this, right, and we are seeing they realize. Let me start with Waylivra first. Even 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 even more than we were expecting in terms of the awareness of FCS in the region. We are seeing a substantial number of cardiologists and other specialty coming up to us and saying, "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. We believe that the Waylivra opportunity in the region is going to be as big as Translarna.
We haven't guided regionally, but you would expect that it's fairly substantial, right? Anywhere in terms of 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. Excited about the product, excited with the potential for revenue in all the key markets there and having some goods early. We have a 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 program is in place.
Feedback from the patients 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's coming through our genotyping program is quite impressive as well on top of the ones that are already identified. Different dynamic because in Brazil alone, we're talking about around 4,800 patients, give and taken, for the hATTR. It's much bigger for 6,000 patients expected in Latin America. Our somewhat, I would say, realistic guidance, as I mentioned on Raju's question, is $150 million for Tegsedi in 2023. We didn't give guidance for Waylivra yet, but you would expect that that's going to be substantial. Appreciate the interest on that and the opportunity to talk a little bit more about these two assets.
You said you had a follow-on?
Yeah. 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 would need to submit that data. I think originally the plan was to submit that data for the end of the maybe third quarter of 2021. That due to a slower pace of enrollment, you've asked for a one-year extension on that. I just wanted to get a sense from you as to why you think that enrollment might be slower than might initially have anticipated.
Yeah. Maybe, go ahead, Marcio. Why don't you?
Of course, Stu. Study 041, in a sense, the enrollment for this study is a little bit tricky, right? Because it is a placebo-controlled study, and we are fairly successful on the markets in Europe and Latin America, for example. There's not a lot of patients available on these core markets for enrollments. We had to expand this to other countries, like in Asia, some countries in Latin America, we are not commercial in the U.S. Originally, some of those countries took a little bit longer to open the sites. While the patients are there, and we're very confident enrollment is going as expected now, as we communicated to the EMA, it was slower to start. It was not an interest or even availability of patients. It was more starting up the sites, requirements for some of them.
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 this study because they were anticipating getting commercial Translarna during the study conducts.
All those factors, we've been informing the EMA, was not simply a submission to them and like, "Hey, we want one 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 in the right direction the last few months with all the sites open.
It picked up quite a bit, and it put us definitely in a comfortable situation.
Okay. Thank you.
Thank you.
Thank you. Our next question comes from the line of Brian Abrahams of RBC Capital Markets. Your question please.
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 your 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 established gene therapy manufacturing program that you're kind of using as a guide or are learning from? Are there any kind of timelines or milestones for this process that we could look for?
Yeah, thanks for the question. I think in terms of the manufacturing, obviously when we picked our CNS gene therapy programs, I think we thought we were pretty thoughtful from the notion of that since you're injecting directly into the region, that the levels of the material that would be needed are less. For example, in the case of what we're doing for AADC deficiency, it's like two times 10 to the 11th, and they're total. It's not like per kilogram, it's just total amounts there. That gives us the opportunity to be able to manufacture, but at a level that we think is really quite doable. Right now, that is not meant for the facility that we'll be going into. That's going to be done by MassBiologics, which we've been working on that with them, and that's going to be our commercial CMO for that.
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 obviously going to be committed to gene therapy. It is an existing biologics facility. It's an operating plant designed obviously for GMP standards. We'll have to make some modifications for this 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, and that includes Friedreich's ataxia, Angelman's, and others that will be moving in. We've started to obviously hire really qualified people who have expertise and experience in this region that will help get us going within that plant.
I think we're in actually pretty good shape to get that ready and go.
Great. Thank you.
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 Alethia. Thanks so much for taking the question. 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.
Yeah, sure. I think 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. We think they're really pretty incredible results in demonstrating the ability of these kids to go in a sense, you've seen a number of them who were basically flaccid children that were capable of walking, that all the kids were able to improve. Now we're just completing the CMC part of that, and that's really just doing the comparability studies and get it all completed to the file by the end of the year. I will reiterate now that we think we're on track for that to be able to complete that. A BLA for AADC will be submitted by the end of the year.
In essence, we feel good that everything's on track, including the manufacturing, to allow us for the BLA.
Thank you.
Thank you. 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 the manufactured gene therapy will be comparable to what was used in the clinical trials?
Sure. Yeah. Marcio why don't you, actually.
Of course. Hey, Joel. How are you? Basically, the process that we used before in the two other sites that produced the material are essentially the same, right? We are using adherent HEK293 here in HYPERStack. That was what is used before. Obviously, that was done in a clinical level. We are looking now into commercial. There was a number of conversations we had with the FDA in terms of what the specs for that, what's the product comparability.
We're not changing process per se, we are looking into the previous drug analytically being comparable to. The two key steps here, I would say missing, there's obviously a number of things that are being done, but the two is, one is analytical methods to commercial grades, release specs that we discussed with the FDA being finalized 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 release, 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 Neo still doesn't have a little bit of time, because he's been running around and making sure everything is absolutely on time and absolutely perfect with his team. They're working very hard. They are doing a great job on getting every step of the way, either on time or ahead of time, we can file the BLA because these patients really need this. Everything so far, so good. We take this very seriously. We want to make sure 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 AADC, and we are driving for a successful launch, we're matching not only the manufacturing in terms of the specs, but making sure we have adequate levels of support for a successful launch in the U.S. and subsequently, globally.
Again, the big picture here is that you didn't change the process from clinical to commercial. There wasn't, in terms of comparability, it's really just saying you have the same materials from the same way you made before. It's almost like a transfer of protocol rather than a different way of doing it. 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. Thanks for that. Then a clarification question on Translarna revenues. They were down this quarter compared to the first quarter of 2018. Was that driven by volumes, or is there a pricing component there?
Yeah, no, there's no pricing components there. That's mostly some orders like in Q4 that came like for Q1 and some timing of orders in Q1 as well. New patients we're getting are younger, so the average price per patient is a little bit lower as well. It's more a mix, I would say, than actually the absolute price of the drug. We're being 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. This includes submitting the first gene therapy BLA for AADC deficiency, the SMA NDA by Roche, the launch of the Tegsedi and Rayaldee 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 risdiplam for SMA at AAN next week. I thank you for joining the call today.
Ladies and gentlemen, this concludes today's conference. Thank you for your participation. Have a wonderful day. You may disconnect your lines at this time.