Good day, ladies and gentlemen. Thank you for your patience. You've joined the PTC Therapeutics 2018 first quarter and corporate updates and financial results conference call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session, and 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, Ms. Emily Hill. Ma'am, you may begin.
Thank you. Hello, good afternoon, and thank you for joining us to discuss our 2018 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 Utter. Before I hand the call over to Stuart, I would like to remind you that today we will be making forward-looking statements.
These statements include all statements other than those of historical facts, including statements concerning financial guidance, our expectations with respect to the future commercial availability of and access to EMFLAZA and Translarna, the timing and outcome of any future resubmission of an NDA for Translarna to the FDA, our future expectations regarding other clinical, regulatory, and commercialization matters, including with respect to potential outcomes and anticipated timelines, anticipated timelines of our SMA collaboration with Roche and the SMA Foundation, addressable patient populations for Translarna and EMFLAZA, and the potential success of Translarna for the treatment of DMD and EMFLAZA for the treatment of DMD.
Actual results may differ materially from expressed or implied by forward-looking statements as a result of a variety of risks and uncertainties, including those related to our commercialization of EMFLAZA and Translarna, including our ability to secure adequate pricing, coverage, and reimbursement terms with third-party payers for our products in a timely manner, whether and to what extent third-party payers impose additional requirements before approving EMFLAZA prescription reimbursement, changes in laws and regulations, our ability to resolve the matter set forth from the denial of our appeals to the complete response letter we received from the FDA in connection with our NDA for Translarna for the treatment of DMD, and those risks discussed under the headings Forward-Looking Statements in our Form 10-Q for the quarter ended March 31st, 2018 and Risk Factors in our Form 10-Q for the quarter ended March 31st, 2018, and in our Form 10-K for the year ended 2017, which is available from the SEC and on our website.
Such statements represent our judgment as of today, PTC undertakes no obligation to publicly update any forward-looking statements except as required by law. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP and non-GAAP financial measures and a reconciliation of GAAP to non-GAAP is available in today's earnings release. With that, let me pass the call over to Stu.
Thanks, Emily, thanks for joining us this afternoon. Joining me on the call today are our Chief Operating Officer, Marcio Souza, and our Principal Financial Officer, Christine Utter. Marcio will provide the commercial and internal clinical development updates. Christine will end the call with a thorough review of our first quarter results and our strong financial outlook. We've had a busy first quarter in 2018. As we recently highlighted at our 20th anniversary Analyst Day, we have several developing programs across the Duchenne franchise, splicing platform, and niche oncology pipeline. Our DMD franchise is growing, with Translarna available in many countries outside the U.S. for nonsense mutation, Duchenne muscular dystrophy, and with EMFLAZA here in the U.S. for all DMD patients over five. Over the past two decades, we have worked to bring therapies to patients with rare disorders, beginning with Duchenne.
We are now expanding on that experience to bring differentiated therapies to patients with high unmet medical need. Our vision is to continue to build a fully integrated rare disease biotech company that leverages our deep science expertise and world-class commercial capabilities. We are now in the position of having two commercial products, we have built an effective global commercial operation. We seek to leverage our commercial platform by continuing to deliver new and differentiated therapies in rare disorders. Our commercial success with both Translarna and EMFLAZA is a reflection of our understanding of the unmet need for Duchenne patients. We work diligently to ensure patients have access to therapies that make a difference to them. Our commercial execution has led to strong year-over-year revenue growth. In the first quarter of 2018, our revenue for the Duchenne franchise totaled $56 million.
Our guidance for full year 2018 is between $260 million and $295 million. We have also set a five-year goal for the compounded growth of Translarna revenue of 15%. Beyond the current growth opportunity for Translarna outside the U.S., we are also looking to expand and bring Translarna to U.S. patients. To that end, we are working to design and initiate a dystrophin study for potential U.S. approval of Translarna. The FDA has informed us that dystrophin data combined with clinical results in our NDA would be sufficient for an application towards accelerated approval. We expect to initiate such a study by the end of the year. Let me now turn to our internal science research programs and our pipeline. I'll start with our internally developed splicing platform. We have an oral small molecule as a treatment for SMA, or spinal muscular atrophy, advancing in the clinic.
This program is currently in pivotal studies in partnership with Roche and the SMA Foundation. The ongoing pivotal studies include FIREFISH for type 1 SMA infants and SUNFISH for type 2 and 3 SMA patients. Encouraging interim data from the dose-finding portions of both studies were recently presented at the annual meeting of the American Academy of Neurology in April. I'll provide more details on that later in the call. In addition to SMA, our splicing platform has generated Huntington's disease and familial dysautonomia programs. These are progressing and are currently in the lead optimization stages. We expect both programs to advance into the clinic by 2020. Our niche oncology program is also advancing. We are focused on rare oncology indications where we can leverage our RNA biology expertise in addressing high medical needs.
There are currently two advanced candidates, PTC596, which is currently in the clinic, and PTC299, which we anticipate will reenter the clinic later this year. I'll discuss these programs in more detail later in the call. Let me now pass the ball over to Marcio, who will update you on our clinical and commercial efforts. Marcio?
Hey, thanks, Stu. 2018 is off to a strong start for our DMD franchise, with two out of the three approved DMD therapies worldwide. EMFLAZA is approved in the U.S. for all DMD patients five years and older, and we are pleased with the progress to date and look forward to further expansion of EMFLAZA use. Translarna is available outside of the U.S. for nonsense mutation DMD patients. As you know, the label for both therapies currently cover patients five years and older. It's well-understood concepts that treating earlier patients with DMD would allow for muscle preservation and therefore better patient outcome. Aligned with our focus on superior care for patients, we are investing heavily in programs to lower the average age of diagnosis worldwide. Currently, patients in most countries have an average delay of diagnosis after presentation of symptoms of more than four years.
We're investing in genotyping and disease state awareness campaigns to improve the standard of care for DMD patients globally. Complementary to that efforts, we're also working to expand the labels of both EMFLAZA and Translarna to patients aged as young as the age of two. Our application for a label expansion for Translarna is under review with European regulatory authorities, and we expect a CHMP decision by mid-year. We are also working to finalize a pediatric study for EMFLAZA in the United States. Now I'll focus on our commercial performance and expectations, beginning with EMFLAZA. We launched EMFLAZA in the U.S. in the middle of May last year. The initial strategic rationale for EMFLAZA acquisition remains the same as we are marching forward to establish EMFLAZA as the standard of care for DMD patients in the U.S.
We are pleased by the SYNERGY ten-year natural history study showing a clear benefit of Emflaza. This was further reinforced by the updated DMD standard of care guidelines, recommending Emflaza initiation at the time of diagnosis. We have completed our first initiative of transitioning deflazacort-experienced patients to commercial therapy, and we are now expanding Emflaza use to the segment of patients who have previously used or are currently on prednisone. We have a number of key initiatives underway to ensure that Emflaza is established as a standard of care in these patients. Additional publications are expected, which will reinforce the benefit of Emflaza over prednisone. Emflaza education programs and conference presentations also allow us to share the data supporting the benefit for DMD patients of Emflaza.
Because of this data, we understand the need to bring Emflaza to all DMD patients as early as possible. We are proud that through an optimized specialist pharmacy distribution and a high-touch patient support programs, we have achieved broad access with low out-of-pocket costs for patients. Reaching naive patients is another critical step in our long-term strategy. It is known that in the U.S., about 50% of the DMD patients are still not currently treated with any corticosteroid therapy. We believe this is a result of the historical view of the risk-benefit of a less safe and less effective drug that predates the Emflaza data publications and our launch efforts. This is now reflected in the current DMD treatment guidelines. We have a long-term strategy to penetrate the segments of untreated DMD patients, as well as to expand the label to address the youngest patients, aged 2 to 5.
Now switching gears to Translarna. As Stuart said, we remain committed to bringing Translarna to the U.S. patients, and at the same time, we continue to expand the adoption globally. We're pleased the FDA has recommended a path forward towards accelerated approval, and our intention is to quantify dystrophin in Translarna-treated patients in two parallel cohorts. One cohort in patients who have been treated with Translarna for at least 1 year, and another one in naive patients. We are currently focused on validating the methods for dystrophin quantification, and we intend to initiate this study by the end of the year, with expected readouts during 2019. Outside of the U.S., we first launched Translarna in 2014. We are confirming our expectation for a 15% composite growth through end year 2022. We're excited about Translarna's growth outlook.
The main driver for future growth will continue to be new patient initiation on Translarna globally. During Q1, we saw growth in patients uptake in all geographies. It's not uncommon in ultra-orphan disorders to continue to identify patients once the treatment is available, and we continue to have success in patient identification in all geographies we operate. Patients and physicians have expressed the benefit of treatment from Translarna, and compliance, as previously reported, has remained very high, over 90%. I'd like to point out, as we have before, that there is a significant variability in the ordering patterns in certain Latin America countries. While we do not guide revenues on a quarterly basis, our annual Translarna revenue guidance of $170 million-$185 million takes into consideration expected variability of these quarterly ordering patterns and reflects the underlying patient demands.
The global commercial Translarna business and EMFLAZA acquisition have diversified our product portfolio, revenue, and geographic footprints, positioning PTC as an outstanding rare disease business development partner. We have now demonstrated the ability to integrate a product and successfully launch in a challenging therapeutic area. As Stu mentioned earlier, one of the goals for our future growth is to be opportunistic in in-licensing and acquiring assets to build out our pipeline, while also invest in our internal developments. Let me now provide a short update on the development programs. As described before, we appreciate the perspective of the DMD community on the importance of treating patients as early as possible in order to preserve muscle function. We plan to conduct pediatric study for EMFLAZA as requested by the FDA. This study, upon completion, would provide us an additional six months of market exclusivity.
We intend to initiate this study in 2018. Additionally, we have completed a PK study of Translarna in children aged two to five. Data from this study was the base of our submission for label expansion to DMD, which is currently under review. Both of these efforts align well with the intent of the DMD guidelines to begin treatment at the time of diagnosis. Our long-term Translarna study, 041, started enrolling patients in the third quarter of last year. As a reminder, the conduct of this study is a specific obligation of our EMA approval, and the FDA has stated this could serve as a confirmatory study in connection with a potential accelerated approval in the U.S. We expect the study to be fully enrolled in 2018 to meet our specific obligation with DMD.
At our Analyst Day in April, I spoke about the strategy of our niche oncology pipeline, and I want to touch more on that today. As Stu mentioned, we are focused on rare oncology indications. We have two lead assets, PTC299 and PTC596. 596, our candidate for solid tumor, was designed to have properties to allow blood-brain barrier penetration and avoid efflux pumps, such as P-gp. That contributes to tumor resistance. This program is currently focused on addressing rare solid tumors with high unmet need. We aim to start new clinical trials in two solid tumor indications this year. The other development candidate we're very excited about is PTC299. 299 is a potent DHODH inhibitor, which is in development for hematological malignancies.
We have prior clinical experience with 299 in solid tumors, which demonstrate good dose linearity and PD response. While generally well-tolerated, two serious events of drug-induced liver injury occur, resulting in clinical holds and the discontinuation of the program in solid tumors. Based on the response we have seen in the clinic, we perform extensive work to better understand the mechanism of action for 299 and identify patient populations with tumor types which are sensitive to DHODH for our clinical path forwards. We found PTC299 demonstrate broader and more potent activity against leukemic cells than against solid tumors, which we expected will enable us to dose at much lower levels in the clinic. We plan to move PTC299 back into the clinic in hematological tumors in the third quarter of this year. We also have a fast-follow DHODH inhibitor currently in late-stage chemical optimization.
We're confident that we are well-equipped to drive value with both strong commercial and clinical capabilities and a continued focus on transforming lives of patients with rare disorders. With that, I'll hand the call back to Stu. Stuart?
Thanks, Marcio. I'd like to share more detail on data recently generated in our SMA program. Most of you are familiar with the program, which is based on our small molecule splicing platform. This technology has been used to discover potential new therapies for spinal muscular atrophy, or SMA, a rare genetic neuromuscular disorder that generally manifests early in life and is the leading genetic cause of death in infants and toddlers. We have a robust program in collaboration with Roche and the SMA Foundation around oral SMN2 splicing modifiers. We believe that an oral systemic therapy provides a competitive advantage because of its broad tissue distribution and ease of administration. Earlier clinical data has been shown that RG7916 drives SMN2 splicing towards a complete restoration of full-length SMN2 messenger RNA.
This program is currently in pivotal stages with two registrational studies, FIREFISH for type 1 infants and SUNFISH for type 2 and 3 patients. The JEWELFISH study, while not registrational, is also enrolling patients from other splicing therapies. Data from JEWELFISH and from the dose-finding portion of FIREFISH and SUNFISH were presented at the annual meeting of the American Academy of Neurology in April. Data from the dose-finding portion of the FIREFISH study included SMN protein level increases of up to 6.5-fold, with a median increase of 3.2-fold. Data from the 21 babies enrolled was presented at the AAN and highlighted continual survival. Previously published natural history data indicate that the median age of event-free survival for SMA type 1 infants to be between eight and ten and a half months. Of the 21 babies presented, nine have surpassed the natural history expectations of 10.5 months survival.
It was also noted no babies have required a tracheostomy or permanent ventilation since study initiation, and no baby has lost the ability to swallow. The median age at first dose was 6.7 months, and babies have received RG7916 for a duration of up to 14.8 months. As of the April presentation, RG7916 has been well-tolerated at all dose levels, and there have been no drug-related safety findings leading to withdrawal. It was previously reported in January that two babies died due to disease progression, and the death was determined not to be drug-related. The FIREFISH dose-finding study is now complete, and all babies are being transitioned to the therapeutic dose for an extension trial. Ongoing data presentation from this trial is expected throughout 2018, including more survival data, CHOP-INTEND scores, and other motor milestones. We look forward to sharing these developing data with you.
As you may have heard from several key opinion leaders at our Analyst Day in April, now that survival data has been presented in SMA babies, the bar has been raised. Physicians and families look forward now to treatment therapies that allow SMA patients to achieve developmental milestones and have broader function. Recruitment is ongoing globally for the pivotal part of FIREFISH study. The primary endpoint of this registrational study is the percentage of infants who are sitting without support at 12 months of treatment as assessed by the Bayley Infant Scale. Presentations on the SUNFISH and JEWELFISH studies also supported safety and tolerability of RG-7916. Data from the dose-finding portion of SUNFISH was also presented at AAN, showing that SMN protein levels increases of approximately 2.5-fold were sustained for up to 35 weeks. In October 2017, SUNFISH entered the pivotal stage and is currently enrolling.
At that time, all SUNFISH patients from dose-finding study were transitioned to the therapeutic dose and have been maintained with no dropouts or serious adverse events. Lastly, preclinical data were also presented demonstrating that RG-7916 increases SMN protein levels in several tissues, including brain, muscle, and blood. These increases were proportional and correlated. These results demonstrate the relevance of SMN protein level increases in blood as the predictor of SMN upregulation in the target organs, such as brain and muscle. The SMA program is not only progressing towards an oral and systemic treatment for SMA patients, it also validates that our splicing platform technology can identify selective compounds that modulate pre-mRNA splicing. We are now applying our expertise to other challenging diseases with high unmet medical need and have internal preclinical programs. These include programs in Huntington's disease and familial dysautonomia.
We expect both programs to enter the clinic by 2020. We are very excited about our splicing programs and covered them in depth at our Analyst Day. I refer you to those slides on our website for full details. I'd like now to turn the call over to Christine Utter, our Principal Financial Officer. Let me pass it over to Christine.
Thanks, Stu. Earlier today, we issued a press release summarizing the details of our financial results for the first quarter of 2018. I refer you to that release for full details. I'll start with a few comments on our financial performance and our guidance for 2018. Starting with our top-line results, we reported strong performance across our DMD franchise. As Stu mentioned, our results for first quarter of 2018 were as expected, with reported total net product revenue of approximately $56 million. Based on where we stand today, we are reiterating our 2018 guidance of $260 million-$295 million. Translarna net product sales were $36.8 million for the first quarter of 2018, representing 39% growth over the prior period, driven by both expansion into new territories and increased penetration in existing geographies.
EMFLAZA net product sales reflect success of the launch, with reported revenue of $19.2 million in the first quarter of 2018, having just launched in May 2017. Total revenues for the first quarter of 2018 were approximately $56 million compared to $26.5 million in the first quarter of 2017. The change in total revenue was a result of the growth of Translarna and the successful U.S. EMFLAZA launch. Non-GAAP R&D expenses were $27.6 million for the first quarter of 2018, excluding $3.7 million in non-cash stock-based compensation expense, compared to $22.9 million for the same period in 2017, excluding $4.5 million in non-cash stock-based compensation expense. This increase in R&D expense reflects increased investment in our research programs and the advancement of our clinical pipeline.
Non-GAAP SG&A expenses were $29 million for the first quarter of 2018, excluding $4 million in non-cash stock-based compensation expense, compared to $20.9 million for the same period in 2017, excluding $4.6 million in non-cash stock-based compensation expense, reflecting continued investment in our commercial activities for our DMD franchise. Net loss for the first quarter of 2018 was $19.3 million compared to a net loss of $29.1 million for the same period in 2017. This decline in net loss reflects our growing revenue base as we continue to leverage our successful international corporate infrastructure. Cash, cash equivalents, and marketable securities totaled approximately $178.3 million at March 31st, 2018, compared to $191.2 million at year-end 2017. In April, we successfully completed a public offering of 4.6 million shares of common stock, raising $117.9 million in the public market.
We intend to use the net proceeds from this offering primarily to transact in potential business development opportunities and to fund and accelerate our research and development efforts, including our programs for alternative splicing and our niche oncology pipeline. I will now hand the call over to the operator and start our question and answer session. Operator?
Thank you, ma'am. Ladies and gentlemen, if you have a question at this time, please press star then one on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Again, to ask a question, press star one at this time. 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 Brian Abrahams of RBC Capital Markets. Your question, please.
Hi there. Thanks for taking my questions. First question on Translarna commercially. Can you tell us a little bit more about whether you saw any inventory effects, seasonality, the impact of ordering patterns in the first quarter, and where you are quarter-over-quarter with respect to patient demand and volume and persistence and compliance?
Hey, Brian. Thanks for the question. Let me get Marcio to-
Yeah
respond.
Hey, Brian. Thank you very much for the question. We did see, as you probably recall, Q4 was a very strong quarter for us last year. We had a lot of demands for both patients and some orders that came very late on that quarter. We had, to some extent, a carryover that is not what I would call inventory building, because you really don't see patients carrying inventory or payers carrying inventory for a long time for Translarna, but there is some effect of that as we transition from the end of the year to this year. The important thing that we've seen as we look into, and what gives me comfort and optimism towards the end of the year is we saw patients being added in every region, as I mentioned a few minutes ago. The compliance is still remaining pretty high.
We're not seeing drop-offs like to the later part of your question. Historically, we've seen more than 90%, so nine, zero, of compliance and persistence, and we are still seeing exactly that same range in all regions. We're adding patients. There is always a little bit of delay here and there at the very beginning of the year. I'm not sure if I was going to call that much as a seasonality effect as it is like just holidays and things like that impacting. Nothing major that we are seeing in terms of the dynamics of the patients. I hope that answered the question.
Yeah, that's very helpful. Then on the U.S. approval-geared studies and investigations for Translarna, can you maybe help us understand a little bit better what the comparison would be for the patients who are on drug for at least a year in terms of dystrophin levels? Would that be compared to baseline levels for the naive group? Would you be using sort of historical data from other sources? Maybe help us understand how that data would all fit together, the naive versus the experienced patients.
Yeah. We would use sort of a combined control that would be untreated patients. What we're looking for, obviously, is to represent what a baseline would look like, and there is some precedent for this in which how Sarepta had done this previously. We would use that as the baseline and compare the treatment of patients who've been on for some time to that control.
Got it. One more from me, if you don't mind. With respect to the SMA program in RG7916, what would you be looking for in terms of the milestone and functional data as we kind of see data evolve over the course of this year at the more therapeutic doses and with longer follow-up? Is there any specific goal? I'm also curious with respect to whether there's any specific symptoms like respiratory symptoms, for instance, that you might be particularly focused on to help us understand whether there's improved brainstem penetration versus available therapies. I'll hop back in the queue. Thanks.
Yeah. Thanks for that. Obviously, we're pretty excited about RG7916, we think it has the potential to be best in class because of the systemic nature of it. I think there's a lot of data now that we've shown pre-clinically how it passes the blood-brain barrier, and that the levels of protein in the blood represent, in a sense, about a one-to-one that we've seen not only in rodents but also in non-human primates as well. We're pretty confident of that as well. Just to remind everyone, we saw up to a 6.5-fold increase in the type 1 babies. We talked a bit about the survival and how we're passing the milestones of that in terms of the eight and a half months, and how 16 babies have surpassed eight and a half month line.
We feel pretty good about that. Over the coming months, obviously, we're going to look at all the motor milestones as well. Hopefully giving about CHOP-INTEND 10 baby sitting, all that will come as it comes through and it gets formally looked at as the data accrues. That's where we're at. That's what we hope to be able to talk about or at least describe as the year goes on.
Thank you. Our next question comes from the line of Gena Wang, Barclays. Your line is open.
Thank you very much for taking my questions. Apologies if some already discussed that I missed the beginning of the call. Just wanted to ask regarding, I think this quarter, any inventory impact stocking, de-stocking for both Translarna and EMFLAZA?
Sure. Marcio?
Hey, Gena. I mentioned this a little bit before. We did see a little bit of, I wouldn't call inventory build-up as I mentioned, in terms of patients getting shipments late in Q4. Obviously the use of that shipment goes through Q1. Just that's the natural use that we see. In some geographies, they end up getting specifically for Translarna, they start getting for more than a month or so. There is a little bit of the spillover throughout the year, but it's not really inventory as much in a strict sense, but they use patterns that we see throughout the year. That impacts a little bit at the very beginning. With EMFLAZA specifically, there isn't much of that dynamic. What we see is really the use and the authorizations happening pretty much throughout the month, at the beginning of the month.
It's harder to ship as well close to the holidays in the U.S., we try to get that all done as early as possible. Not as much, even for these small amounts that are described for Translarna, we don't see that happening for EMFLAZA.
Any more color regarding, I don't know if you comment earlier, regarding the number of patients beyond the initial bridging programs, like new patients for this quarter for EMFLAZA?
Sure. We stopped disclosing specific patient numbers in Q3 last year, just to give you a little bit of color on that. We've seen growth in patients. We're pretty happy with what we are seeing in terms of activity from the fields. The programs we put in place, we moved to this what we call the phase II of the launch now. Pretty much the bridging that you mentioned before and the patients who are previously experienced with deflazacort, they've been transitioned. What we are seeing more and more now is in this phase II, as I described, is patients who are being treated with prednisone, prednisolone, or any other forms, that there's a lot of stuff, a lot of ways these patients are being treated. It's starting treatments, it's staying on that treatment.
We are pretty happy with the trajectory that we are seeing right now. Obviously, the work does not stop, and we're looking every day on how to make this better and how to get more patients on what we believe ultimately is best for them. It's the only approved treatment in the U.S. and the best standard of care.
Okay. Thank you. Just one quick question regarding SMA program. Can you just remind us, in terms of a rough timeline that you and/or Roche will present the SMA functional data? Also, if you can just remind us, in terms of onset of the drug, once you start to dose the patient, how quickly you will start to see the protein level increase, and then that could translate into the clinical benefit?
Yeah, sure. Thanks for that. Just to remind, as we were talking about a little bit ago, that we have the SUNFISH type 1 study, the part 1 where we talked about previously where we had six of the 21 babies we talked about previously, two had passed that were non-drug related, and that 16 babies already are alive with the key milestone of 18 and a half months. Just to remind everyone that the median age of enrollment was about 6.7 months, and they've been on drug for up to 14.8 months. What we're going to be doing is going to be presenting data throughout this year. Obviously, we're excited about that. Stay tuned.
We'll be going from not just survival data, but going to then we'll be talking about the motor function milestones and measurements like CHOP-INTEND, put out baby sitting, other things. Talk about all the important milestones that we'll be measuring throughout the year. We intend to have such discussions as we see them and decide that we need to present them, describe them, or to have them at scientific meetings. That's our plan. We plan to have hopefully a significant number of discussions with you over the year.
Okay. Just a quick question regarding how quick onset the drug, once you start to dose the patient. Yeah.
Yeah. Obviously, it's an orally bioavailable systemic drug that gets into all tissues. We saw in blood that it occurs actually quite rapidly, where you start seeing a production of the protein. You give it for a day, you get RNA made, and then from there you get protein relatively quickly. You can measure quite rapidly.
Okay. That happen usually in days, right? You will be able-
Yeah
to see? Okay.
That's correct.
Okay, great. Okay, thank you very much.
Thank you.
Thank you. Again, to ask a question, please press star one at this time. Again, that's star one on your touchtone telephone. Our next question comes from the line of Raju Prasad of William Blair. Your line is open.
Thanks for taking the question. Sorry if I missed this. Hopped on the call a little late. As far as the dystrophin study for the U.S., have you met with the FDA yet, or do you have any kind of incremental color on the type of data that you'll have to submit, and potentially from what parts of the body or what muscle types?
Sure. Marcio wants to take that.
Yeah. Thanks for the question. We've been talking to the FDA. Well, I'll be very happy with the openness that the agency have had with us in terms of being even a little bit more informal on some of the communications and keeping the door open for back and forth that we might require with them. As we mentioned late last year, that we would be talking to them during Q1, and we do regularly talk. What we are focusing right now, really, with our understanding of some of these conversations is that the key is really for us to pick the methods, continue collaborating with them, and understand what the decision wants to do in terms of the qualification. We are running a few tracks in parallel based on that.
We have some stuff we did in-house and some collaborations we are doing externally with private labs as well on the quantification. That's the rate limiting. As I mentioned before, and we discussed at the analyst event on April 17, we expect to start this trial in the U.S. before the end of the year. We see no issues whatsoever right now on march towards that date, and it's really a parallel track between the clinical initiation and the methodology to be validated.
Great. Just a quick question. In the press release for the part 2 of the FIREFISH study, the endpoint is the proportion of patients sitting without support after 12 months of RG7916 treatment. Does that assume that the patient's median age is going to be around six months? I thought it was kind of an 18-month endpoint for other companies.
No, right. It's the number of patients sitting after 12 months and unassisted for five seconds.
That's agnostic to the age they are when they're enrolled in the study. If it's one or two month old, it would be when they're 13 or 14 months.
That's correct. I think it's important for us to remind here, right? If you look into part 1, these patients were fairly old, and they had to be symptomatic at three months, no later than three months. What is a little bit different when you look into other data sets that are out there, these are what we call type 1. These are the most severe type 1 patients. We are seeing the mean age, sorry, the median age on the last slide that we showed you guys was 6.7 months. Independently of all of that, and we discussed this before, we're very confident on how this study is going, and we're looking forward to show that. It's irrestrictive of, to answer our question directly, irrestrictive to the dates they are enrolled, is 12 months after enrollment.
Maybe just as a little color to that, part of the reason we chose that they had to be being diagnosed by three months because it is an open-label study. That really sort of defines them as a truly type 1.
Great. Thanks.
Welcome.
Thank you.
Sorry. I was just going to put one point. As the outcome of that is we're looking for a five or greater out of 40 would be statistically significant.
Thank you. Our next question comes from the line of Joel Beatty of Citi. Your line is open.
Hi, thanks for taking the questions. First one is on the SMA program. Could you share any data to date on the differences between dose levels that you saw in part one of the study, including any information you might be able to provide on how the eventual dose that was chosen for the pivotal part of the study was chosen, as well as any implications from the dose finding study in terms of the effects you might expect to see in the first patients that were enrolled compared to the patients that were enrolled later in the study?
Yeah, sure. I think, obviously the first part was really a dose finding study. Really the doses, we're looking both at variables such as age and weight as part of that. Once we completed that portion, we're now moving them up to what we think is the efficacious dose and following them from all those from there. I think that's sort of the point where everyone is on equal playing field in the sense of having the same dose is now occurring. They all weren't on the same dose, and we were picking the dose really based on, we had the advantage of having a PD marker that lets us look at the level of SMN protein. You really could actually get, define how well you're doing by that dose. That was the key part of this.
Got it. One other question. On the 15% growth this year from Translarna, could you give any color on is this expected, kind of across the board or what particular regions or groups do you expect to contribute to that growth the most?
The 15% composite growth until 2022 that we gave as a guidance, the expectation there on the base is really driven by patient accrual. We expect to continue to accrue patients globally. What we are seeing right now, what our projections show, what the programs we've put in place are supporting is that this growth is going to continue to come for all geographies that we operate. Beginning of the year, on the last couple of months, we're seeing this materialize in all the geographies. We're happy with the progress on patient identification. We're happy with the progress in terms of genotyping. As we expand, obviously in the later years, the remaining patients and the more percent-wise growth is going to come for the regions that are less penetrated, like the Middle East and Africa, CEE, and Latin America.
In general, all the regions are growing. They're all included in the potential. I think it's worth to mention as well, as I talked in the remarks a few minutes ago, we are in the last stage of the conversations with the EMA for the label expansion for the two to five, and that's going to add more patients to the pool. We're going to be able to treat them globally, and we hopefully are going to be resolving this in the next couple of months with the EMA and going to be able to launch the product later this year or beginning of next year and start to accrue patients.
Great. Thank you.
Thank you.
Thank you. At this time, I'd like to turn the call back over to Stuart Peltz for any closing remarks. Sir?
Hey, thank you. Thank you all for joining the call. As you can see, we're pretty excited about 2018, and we think this is going to be a really important year for us with several milestones that we think are going to potentially drive value creation. We'll continue to grow the Duchenne franchise. We're going to present additional data from our SMA program, and we'll be sharing more on the oncology pipeline. In addition, it's our goal to do at least one transaction in business development this year to add something else on. I think there's a lot of value generation to occur, and I thank you for joining the call today.
Thank you, sir. Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day.