Seeking Alpha
We cover over 5K calls/quarter
Profile| Send Message| ()  

Executives

Erin Cox - Manager of Investor

Chris Garabedian - President and Chief Executive Officer

Analysts

Bill Tanner - Lazard Capital Markets

Chris Marai -Wedbush

Lisa Bayko - JMP Securities

Ed Tenthoff - Piper Jaffray

Kim Lee - ThinkEquity

Sarepta Therapeutics Inc (SRPT) 48-Week Results From the Phase IIb DMD Study October 3, 2012 8:00 AM ET

Operator

Welcome to the Sarepta Therapeutics 48-Week Results Conference Call. My name is Jo, and I will be your operator for today. At this time, all participants are in a listen-only mode. We will conduct a question-and-answer session towards the end of this conference. (Operator Instructions). As a reminder, this call is being recorded for replay purposes.

I would like to hand the call over to your host Ms. Erin Cox, Manager of Investor Relations. Please proceed.

Erin Cox

Thank you, Jo, and thank you for joining today's call. Earlier today, we issued a press release detailing 48-week results in our Phase IIb DMD study. The press release and the slides we will be presenting today are available on the news and events section of the investor relations portion of our website at www.sareptatherapeutics.com.

Joining me on the call today is Chris Garabedian, Sarepta's President and Chief Executive Officer, and Ed Kaye, our Chief Medical Officer.

I would like to note that during this call, we will make a number of statements that are forward-looking including statements about the development and clinical status of Sarepta's product candidates, including eteplirsen and the potential efficacy and clinical results.

These forward-looking statements involve risks and uncertainties many of which are beyond Sarepta's control. Any such risks could materially and adversely affect our business, results of operations and the trading price of Sarepta's common stock. For a detailed description of risks and uncertainties we face, you are encouraged to review the company's filings with the Securities and Exchange Commission.

With that, let me turn the call over to Chris Garabedian, Sarepta's President and Chief Executive Officer. Chris?

Chris Garabedian

Thank you, Erin, and I am very excited to share some important news today about eteplirsen, our drug for the treatment of Duchenne muscular dystrophy. Specifically, I'll be sharing new 48-week data from our Phase IIb extension study that strongly supports the potential for this drug to treat the underlying cause of this devastating genetic disease and to slow its progression.

The data I will share today seems to confirm that treatment with eteplirsen results in robust and consistent levels of dystrophin as a percentage of positive muscle fibers, the essential protein that Duchenne muscular dystrophy patients are lacking and that this novel dystrophin production is translating to a statistically significant clinical benefit for patients.

We believe these results provide tremendous promise to patients with Duchenne muscular dystrophy and we know that the production of dystrophin is a critical protein lacking in the patients that prevents healthy muscle function and growth.

Before I provide an overview of the 48-week results described in a press release this morning, I would like to mention that we are looking forward to sharing more details from this study at World Muscle Society Meeting in Perth, Australia. On October 13th, in a late breaker oral presentation that will be presented by Dr. Jerry Mundell, the principal investigator of our Phase IIb study at the meeting.

We have slides that are available on our website for viewing during the call today. This first slide is meant to provide an overview of the design of Study 201 and Study 202, which is the open label extension study, and the data that we'll describe today has been derived from these studies.

Today, we will be describing dystrophin data from the 48-week biopsy results, and additional 6-minute Walk Test data through 48 weeks. The patients in this study will continue to receive drug and we will continue to capture safety assessments weekly and clinical outcomes including 6-minute walk test data every 12 weeks.

If you refer to the next slide, slide three, I will now provide an overview of the results that were detailed in our press release this morning. The primary efficacy endpoint defined in our protocol and statistical analysis plan of Study 202, which is our long-term safety and efficacy extension study was the increase in dystrophin positive fibers as a percentage of normal compared to baseline.

At 48 weeks, eteplirsen administered once weekly at either 30 mg/kg, or 50 mg/per kg for 48 weeks resulted in a statistically significant mean increase in dystrophin positive fibers of 47% as a percentage of normal across all treated patients with a p-value of 0.001.

There was no significant difference between the 30 mg/kg, and 50 mg/kg arms on the production of dystrophin through 48 weeks but all patients demonstrated high levels of dystrophin positive fibers that ranged from 30% to 60% of normal across these two dose groups.

The placebo delayed treatment cohort which had received 24 weeks of eteplirsen at either 30 mg/kg or 50 mg/kg following 24 weeks of placebo also produced a statistically significant mean increase in dystrophin positive fibers of 38.3% as a percentage of normal with a p-value of less than or equal to 0.009.

The previously reported cohort of patients who were administered eteplirsen once weekly at 30 mg/kg over 24 weeks that resulted in a statistically significant increase in novel dystrophin of 22.5%, which was presented at The American Academy of Neurology Meeting in April. These patients showed an additional increase of approximately 30% additional dystrophin positive fibers between weeks 24 and 48, for a mean of 52.1% dystrophin positive fibers at week 48

This legs further evidence that dystrophin levels in the muscle continue to increase with continued treatment with eteplirsen. This increase was highly consistent across these four 30 mg/kg patients and ranged from 28% to 31% additional dystrophin positive fibers between weeks 24 and 48 across these patients.

Overall, we are very encouraged by the consistent high levels of dystrophin seen across all of the patients in the study with patients who received eteplirsen for 24 or 48 weeks with the added evidence of increasing dystrophin levels with continued dosing as evidenced by the four patients I described at the 30 milligram per kilogram cohort.

The next slide shows new 6-minute walk test scores at 48 weeks. In study 202, our long-term safety and efficacy open label extension study, we conducted our pre-define prospective analysis of the studies intent to treat population on the primary clinical outcome measure which was defined as the change in 6-minute walk test distance from baseline.

Eteplirsen administered once weekly at 50 mgs/kg over 48 weeks resulted in a 21.0 meter improvement from baseline on the 6-minute walk test compared to a decline of 68.4 meters in the placebo delayed treatment cohort. Again, these patients in the placebo delayed treatment cohort received placebo for 24 weeks followed by 24 weeks of treatment with eteplirsen in the open label extension.

This difference resulted in a statistically significant clinical benefit of 89.4 meters on the 6-minute walk test and achieve a statistical p-value of less than or equal to 0.016. This treatment benefit is unprecedented in DMD and translates to a significant delay of disease progression based on this standard well accepted measure of ambulation and give us a strong signal that long-term treatment with the eteplirsen may yield a long-term benefit of maintaining healthy muscle function and significantly slowing or halting progression of this disease.

As a reminder, we were very particular in setting up the study's inclusion criteria to select a patient population that would be likely to decline over a 48-week period by not allowing younger patients below the age of seven into the study as well as not allowing healthier patient based on higher 6-minute walk test at screening.

The improvement in 6 minute walk test over 48 weeks is even more impressive given that we enrolled patients that we expected would see significant decline over 48 weeks. As we've described previously, we had two patients in our 30 milligram per kilogram weekly eteplirsen cohort that showed rapid progression of disease on measures of ambulation shortly after enrollment in the study, and these patients were unable to complete the 6-minute walk test by the 24 week time period, and are in a non-ambulant state beyond the 24 weeks.

The 30 milligram per kilogram cohort that included the two non-ambulatory patients was also assessed in the intent to treat population and was not statistically different than the placebo delayed treatment cohort on the 6-minute walk test through 48 weeks. When we announced the 36 week data, we analyzed our 6 minute walk data using our modified intent to treat population in which we excluded the two patients in the 30 mg/kg weekly eteplirsen cohort in a non-ambulant state.

If you look at the, next slide now on the webcast, you will see a fourth plot highlighting various subgroups of the modified intent to treat population. We originally showed this analysis for the 36-week 6-minute walk test data and have now updated with the 48-data.

In this analysis, we looked at subgroups by dose, age, baseline 6-minute walk test and genotype across the modified intent to treat population, and there was a benefit, a numerical benefit across every subgroup in favor of the eteplirsen treated patients that ranged from approximately 30 meters to more than 90 meters. Among the subgroups, greater benefit were seen in the younger patients and in patients with higher baseline scores on the 6-minute walk test as both of these subgroups had more pronounced treatment benefit of 69 meters and 94 meters, respectively, which resulted in a high level of statistical significance with respect to p-value of 0.38 and 0.001.

Lastly, we looked at response by genotype, and at 48 weeks there was no evidence that a treatment effect may vary by genotype. There were five genotypes that were amenable to an exon-51 skip represented in the study and the most common was the 4950 deletion where five patients were represented, three placebo delayed treatment and two eteplirsen treated patients. In this population, we saw at 83-meter benefit in this genotype cohort favoring the eteplirsen treated patients who increased 14 meters from baseline over the placebo delayed treatment patients who decline 69 meters from baseline.

Lastly, we also completed a full review of the safety profile of eteplirsen across all subjects through 48 weeks and there were no treatment related adverse events, no serious adverse events and no patients have discontinued therapy. Furthermore, no treatment related changes were detected on any safety lab parameters including several biomarkers for renal function. In summary, building on the 24 week dystrophin dataset and the 36 week 6-minute walk set, we have now demonstrated over a longer period of treatment 48 weeks that we have successfully delivered on the three key elements that we believe position he eteplirsen as the most promising disease-modifying drug in development today for the treatment of Duchenne muscular dystrophy.

First, we have demonstrated that eteplirsen administered weekly at either 30 mgs/kg or 50 mgs/kg for 48 weeks resulted in a statistically significant increase in novel dystrophin with an average of more than 47% dystrophin positive muscle fibers as a percentage is normal.

Second, we have demonstrated that this novel dystrophin production is translating to a statistically significant and unprecedented clinical benefit with eteplirsen treatment once weekly at 50 mg/kg over 48 weeks resulting in an 89.4 meter benefit compared to the placebo delayed treatment cohort. And third, we have demonstrated a highly favorable safety profile through week-48 with no the eteplirsen related adverse events seen which is a very important characteristic given that Duchenne muscular dystrophy would require long-term lifelong treatment.

If you look at the next slide, I want to highlight as we did with the 36-week data that the clinical benefit we've seen with eteplirsen is quite remarkable compared to other drugs and therapeutic areas that have used the 6-minute walk test as a component of the primary endpoint. For example, the most advanced disease modifying drug in development for Duchenne, ataluren demonstrated a 30 meter benefit after 48 weeks of therapy. Additionally, there were three drug approvals for other rare diseases that had a 6-minute walk test benefit that ranged from 28 to 30 meters over different time periods.

As a next step, we, with this 48 week dataset in hand, we will be preparing for and end of Phase IIb meeting with the FDA, and will be requesting a meeting to occur around year end or early next year to discuss the most expeditious path toward product approval. We are also investing in manufacturing scale up to prepare for additional clinical trial commitments and the potential for an eventual commercial approval of the drug.

I just want to close by stating that we at Sarepta Therapeutics, are obviously excited and thrilled by these results as we believe they confirm that eteplirsen represents a potentially unparalleled medical advancement for the treatment of Duchenne muscular dystrophy. We are acutely aware of the urgency with which this drug is needed and we will continue to work tirelessly to advance eteplirsen with the ultimate goal of securing regulatory approval, so that this therapy can be made available to all DMD patients who are desperately waiting for the safe and effective treatment.

Operator, that concludes my prepared remarks and we can open up the call to questions.

Question-and-Answer Session

Operator

Thank you. (Operator Instructions). First question comes from the line of Bill Tanner from Lazard Capital Markets. Please proceed.

Bill Tanner - Lazard Capital Markets

Two questions for you. One is on immunoblot, wondering if data would be presented at the World Muscle. Then the second as it relates to looking at the 6-minute walk data for the various subgroups, if you look at the eteplirsen treated patients, looks like it's better, works better than the high versus the low baseline. 6-minute walk baseline, I guess one for instance drug works better less disabled patients, but another would be the dose and I am wondering if you could comment on what's the distribution of the 30 and 50 mg/kg doses across the high and the low.

Chris Garabedian

Sure. First on immunoblot data, Bill. We literally got this dataset this week, and so we worked very rapidly to turnaround the top line data which we guided a that would be what we would prepare first and foremost for of the World Muscle Society meeting, so we will be working over the next week to mine the data further. We did not finalize any analysis on the other biochemical markers at this time and so it's difficult to predict what exactly we'll have pulled together by World Muscle, but we will be looking further at the dataset. We wanted to focus on the primary outcomes for this initial press release.

We are not going be sharing the individual patient data, but I am comfortable providing a lot of color around the description, so although we will not break out how many of those subgroups were in 30 milligrams versus 50 milligrams, I can tell you that the trend continued that the younger patients and healthier patients as defined by 6-minute walk test, had better treatment benefit, but I don't believe that there's evidence of a dose response or that we can glean what the best dose is based on the 6 minute walk data.

I think the dystrophin levels that we're seeing, which are very consisting, in fact you can see in the press release that the 30 cohort actually had a higher level of dystrophin positive fibers than the 50 milligram cohort, and we believe that is the stronger marker of dose response or lack of a dose response and we believe that these are dystrophin levels that are beyond the threshold where we would expect functional improvement and impact on the progression of the disease, so we will continue to follow the clinical outcomes but we believe that dystrophin is very telling that there does not seem to be and there is no statistical difference between 30 milligrams and 50 milligrams, so we're going to be continuing to evaluate the data by dose cohorts, but at this time we have not included what the best dose is to bring into registrational trials.

Bill Tanner - Lazard Capital Markets

So, I think that your comment is that the 30 mg/kg could very well be an effective dose, and just obviously small numbers of patients, so you are still believing there is a good correlation between dystrophin being produced in the clinical benefit.

Chris Garabedian

That's right.

Bill Tanner - Lazard Capital Markets

Okay. Thanks very much.

Operator

Thank you. The next question comes from Chris Marai from Wedbush. Please go ahead, sir. Your line is open.

Chris Marai -Wedbush

So, we've got a couple of questions here. One, regarding the dystrophin production did you guys have a chance yet to look to see if that was correctly localized in the biopsies and settings that you had done?

Chris Garabedian

Yeah. We will be preparing much like we did for the AAN Meeting in April. Each of the individual slide, so we will have at of pre and post know your immunofluorescent slide for each patient in the study, and will be presenting at World Muscle, so we were very encouraged just a qualitatively looking at the slides, was very impressive even in the 30 milligram of patients who we had 24-week immunohistochemistry and 48-week. You can even see the progression of additional dystrophin that's produced.

Again, we were very encouraged by what was localized. We've not done the testing as we've done with previous studies and previous biopsies of looking at the other glycoproteins that make up the dystrophin glycan complex, but there is no reason to believe that we are not making the same functional dystrophin that we saw evidenced in the 24-week biopsies that Jerry Mundell conducted as well as the additional work that was done with Francesco Muntoni published of from our IM study originally.

Chris Marai -Wedbush

Great. Then on those two boys that progressed rapidly earlier in the study. Any insight into what their dystrophin levels were like relative to the other boys? Did that compare well or was it lower, higher?

Chris Garabedian

Yes. I mentioned in my comments that we were very encouraged by the consistency of the increase in the 30 milligram cohort patients and that includes the two boys who were non-ambulant. All of those four patients in which we saw dystrophin levels at 24 weeks, increased their dystrophin positive fibers by a range of 28% to 31% additional and that includes those two non-ambulant boys. Again, we saw very nice increases across all of those including the non-ambulant boys.

Chris Marai -Wedbush

One last real question, a follow-up on at the market facility, is there any update on just how much of that you guys have taken down or when you may provide us an update on?

Chris Garabedian

Yes. Chris, as you know, we can use that at our discretion and we are not required to disclose how we use that or if we do that facility until our November earnings, so at this time we are not providing any comment on the…

Chris Marai -Wedbush

Okay. We look forward to that later. Thank you then and congratulations on the data.

Operator

Thank you. The next question comes from Lisa Bayko from JMP Securities.

Lisa Bayko - JMP Securities

I would also like to reiterate my congratulations. Quite remarkable. Are you just along the lines of the patient mix, are you going to be presenting sort of the baseline demographic data at the meeting next week?

Chris Garabedian

Yes. Lisa, as you know the baseline demographics haven't changed, and so those baseline demographics were presented at the AAN meeting in our poster presentation. Again, those have not changed and they will be represented at the World Muscle Society meeting.

Lisa Bayko - JMP Securities

Okay. Just to dig down that further, we won't necessarily know which patients crossed over. We won't be able to track those necessarily?

Chris Garabedian

You will. As the cohort, so the placebo cohort the 30 mgs and the 58 mgs were characterized with baseline characteristics and so will have that as part of the oral presentation late-breaker oral session, and also in the press release we provide the baseline 6-minute walk and for the subgroups by the age cohorts at baseline in those subgroups and the baseline 6-minute walk test by the subgroups in both of those characteristics for the genotype subgroups, so there is a lot of baseline characteristic data from the AAN poster as well as in our press release.

Lisa Bayko - JMP Securities

Okay. Thanks. Then for the 6-minute walk test. I know you also repeated measures test, so how do we think about the individual data points as we look at let's say the chart that's in your slide deck? Is the repeated measures just to get to the p-value or how do we use that to read the actual curves?

Chris Garabedian

Yes. So, again you're referring the intent to treat analysis, I presume, in the line graph. Yes, so that was a mix model repeated measure and we again described this when we presented the 36-week data and our statistics around that in which if there is a violation of normality in the intent to treat population of which are was because of these two boys who showed the rapid progression that we would apply the ANCOVA rank data, and so that is the predefined statistical analysis that was defined in our SAP for both, Study 201 and Study 202, and so again that's what we did.

Now the mix model as you know takes into account all of the data points, right? That collected at each time point and it did basically puts a fit curve right? It provides a slope, base on all of those data points. The FDA prefers this type of analysis, because they don't want any conclusions being drawn where you may have a baseline value, and then let's say at 48 weeks you happened to get lucky and all of a sudden everybody looks better, but it's belied by all the data points in between, so that is probably that the best layman's description. I am not a biostatistician, but that's the methodology that was used. There was again high level consistency and that is what drove the p-value.

Operator

Thank you. The next question is from Ed Tenthoff from Piper Jaffray. Please proceed.

Ed Tenthoff - Piper Jaffray

Really sincere congratulations. I know this is just a phenomenal day for Duchenne patients and all the hard work and frankly decades of labor that have gone into this. I couldn't be personally more pleased from what you guys have accomplished today.

A couple of couple quick questions. Just kind of looking back at some of prior data release, it looks like there were some minor changes in the 50 mg/kg 6-minute walk test. I am looking back to the data that you reported back in July. Again, it's only a couple single-digit meters here and there, but is there anything to account for the slight changes?

Chris Garabedian

Yes. Actually, Ed I am glad you brought it up. When we do this mix model repeated measure test, every data point, right? Will affect the overall slope of the curve for each cohort, all right? And it does allow interaction, so it will basically be influenced also by how each cohort is doing in terms of how to affect the slope of that curve. So, for each data point that we add, we may and likely will see a slight variation. For example, because the placebo group for example, showed an average increase from the 36-week time point, that kind of pulls up the slope a little bit and that's why the decline at 36 weeks was not quite, right, where it was when we just had the 36-week data point. Okay?

And, so that's common and I'll also add and you can see that we highlighted this at the 36-week time point. When we don't include the two outliers, as we have in our modified intent to treat, the numbers can change. Again, directionally, they are the same, but numerically it can change slightly and it will affect p-value particularly when the pullout outliers as we did in the modified intent to treat.

Ed Tenthoff - Piper Jaffray

All right. That's really helpful. If I may just a follow-up, and I know this is a fresh off the presses here you probably haven't gotten the whole plan work for you yet, but on the PDUFA V, how would you anticipate a conversation with the FDA going next year? Can you give us any color on that?

Chris Garabedian

Yes. Well, let me just reiterate what I've stated previously. It's that we would look at the 48-week data to determine our strategy and going into end of Phase IIb meeting with the FDA. I can tell you based on the results we have in hand today that it's very encouraging and we are very excited to pull this into briefing documents to have a conversation with the FDA about the fastest path toward approval of this drug.

Related to the data of PDUFA V, obviously accelerated approval for rare disease was highlighted, and you know there are several characteristics that are described in what qualifies for consideration under an accelerated approval filing, but one in particular is that you have evidence of this surrogate marker that would reasonably predict a clinical benefit and we believe we have two things going for us.

One, is we have a very clearly defined surrogate right? In the Duchenne population which is dystrophin, right It's the cause of the progression of the disease, and I think there is very little argument about the role the dystrophin plays in Duchenne, so we have a surrogate marker that we've hit a statistical significant endpoint at both 24 weeks and now 48 weeks. And now with the crossover population, but we also have a clinical benefit which is not necessarily required for an accelerated approval, and so again we're encouraged by the data so far and we look forward to talking to the FDA, but we will not make any definitive decisions about an NDA filing until we have that conversation with the FDA, but obviously this dataset gives me a lot more confidence in having that conversation.

Ed Tenthoff - Piper Jaffray

Fantastic. Again, congratulations. Really exciting stuff.

Operator

Thank you. The next question comes from chimney from Kim Lee from ThinkEquity. Please proceed.

Kim Lee - ThinkEquity

Good morning, and I'd like to add my congratulations as well on this excellent data. Just a couple of questions here. Going forward whether it'd be a confirmatory trial or Phase III trial, what do you see now given this data could be a potential design for a Phase II or a confirmatory trial? Specifically, how many patients you think you will need and, especially how many patient do you need to fulfill the safety requirement for the FDA and then I have a follow-up after that.

Chris Garabedian

Sure. So, obviously, we wanted to wait until we had this data set before we start thinking about the no final proposals that we would bring to the FDA in terms of confirmatory evidence of what were seen in the study. There are a lot of issues to consider as we think about a confirmatory study.

Clearly if this would qualify under an accelerated approval or early full approval filing then that could confound our ability to enroll a placebo-controlled study. I think the DMD community might not want to enroll in a placebo-controlled study in of progressive disease like this if they believe that the drug would be made available or worse, if there enrolled in the placebo-controlled study would they drop out if the drug were approved during that study.

So, I think we are exploring a variety of possibilities of providing confirmatory evidence. We know that the FDA has approved drugs in indications for drugs without placebo control, and we know that you once we have a controlled study like we have here and evidence you know we think that there may be some room to have a dialogue about other alternatives to placebo-controlled such as an untreated cohort in patients with DMD who would not qualify for eteplirsen. There may be other design parameters.

So, Kim, I'd say we're still evaluating that. The treatment effect give us confidence that we could probably keep the overall sample size relatively low. We've guided previously that we think a 60-patient study would be sufficient for confirmatory evidence. Again, we'll continue to work with her biostatistician to figure out what the appropriate powering would be of the study and we know that there is a lot of precedent for a drug approvals in rare diseases with of safety databases of less than 100 patients or less than 60 or 50 patients.

So, that's coupled with the fact that were seen a very favorable safety profile today, so I am sure that has a factor, so I'm sharing all of this because I want to highlight that there are a lot of different dials here and a lot of different considerations that we and the FDA are going to have about how to look at this drug on its own, right? Looking at precedent and looking other rare diseases, but this data set should be the thing that informs those decisions the most moving forward.

Kim Lee - ThinkEquity

Great. Thank you for that granularity. And just a couple of details on the study here, can you remind us first how many patients in total have been exposed to eteplirsen. Second, what was the cut-off range for the 6-minute walk test criteria?

Chris Garabedian

Yes. Total exposure to eteplirsen across the three studies are four now accounting Study 202 that we've done. We have a 12 patients always exposed at the highest levels that have ever been dosed in this study. In the dose escalation study, we had 19 patients exposed to the drug and 17 patients in which we received biopsy with some evidence in the patients of dystrophin production and then we have seven patients in the original intramuscular injection, where we show a strong evidence of dystrophin production locally and that it was a functional dystrophin, so the total that we had exposed now was 38 patients total.

Kim Lee - ThinkEquity

Great. Then 6-minute walk test entry criteria?

Chris Garabedian

Yes. The entry criteria at the screening visit that they had to walk between 200 and 400 meters, and we allowed a 10%, okay, swing in that. Now most of the patients were in the higher end of that range, and in fact a couple actually were above the 400 meters, but they couldn't have more than 440 meters to qualify for the study for that initial baseline visit.

I'll add that we collected two 6-minute walk test at baseline as well as a 12 weeks and 24, and we predefined that we would use across every patient the highest 6-minute walk score at baseline at every time point, and that includes the placebo patients' best score as well as the treated patients' best score. The trends remain whether we look at average 6-minute walk test or lowest scores, but we predefined highest and those are the values that we are describing in all the data today.

Kim Lee - ThinkEquity

Great. Thank you. And one follow-up on manufacturing here, can you give us an update on manufacturing and also if any of your timelines have changed as far as plans to initiate confirmatory or Phase III given the manufacturing side? Thank you.

Chris Garabedian

Yes. I previously guided that we are preparing for midscale production, okay? We have been producing drugs in small scale batches for continuing the 12 patients in our current study, and we knew that we would have to move to midscale production to supply drug for, A, clinical study of which I have described let's say about 60 patient or so. Those plans are in place and we had previously guided that we would start enrolling that study in the second half of 2013, and be prepared to start dosing in early '14.

Depending on our conversations with the FDA, and the prospect and likelihood of a commercial approval or early approval of the drug, we already are thinking about how we would start to scale up for large-scale production of which we believe would want to have for to meet the demand upon a commercial approval of the drug. We announced it in 8-K in early September, that we have engaged a contract manufacturer to start some of that scale up or using other manufacturing suppliers as well to start preparing for this need for more drug production. That's all we have to say right now.

Kim Lee - ThinkEquity

Great. Thank you and congrats again.

Operator

Thank you. We do have another question. That comes from Ren Benjamin of (Inaudible) & Company. Please proceed.

Unidentified Analyst

Hi. Good morning, Chris, and thanks for taking the questions and congratulations again on outstanding data. A quick couple of questions. One, can you help us understand little bit more the importance or lack of importance of a dose response and maybe what you've learned from these the expression of dystrophin, the different doses that are being administered here and what a potential minimum dystrophin expression or intensity, how those might play a factor here, especially when trying to correlate with a 6-minute walk test?

Chris Garabedian

So, Ren, when we designed the study, we spoke to a lot of experts in the field and there is a lot of debate about what role each of these different measures whether it's a western blot, whether it's dystrophin intensity, dystrophin positive fibers, and based on all of that we predefined that the most important of all of those was the looking at the actual muscle tissue and where the dystrophin is localizing and where you we see it in a circle them in the cell membrane that the dystrophin positive fibers seeing a good well distributed kind of diffuse a dystrophin in a muscle biopsy would be the most important.

We knew that you would have to have at least the minimum threshold of dystrophin intensity per fiber to be able to see it on the immunohistochemistry staining. We are continuing to analyze these other biochemical assays for dystrophin. And again, we have not finalized or completed that analysis at this time, but we defined the primary endpoint as the percent of dystrophin positive fibers using the anti-dystrophin MANDYS106 antibody and that's what we reported here. I think, again, this would beyond our expectations based on the previous data that we saw going back to the U.K. study from even the 24-week data and it appears that we have a consistent dystrophin production across different patients across different time point and across different dose groups. They are all within a good range and we had some in the 30 milligrams that were higher than some in the 50, obviously, and we had some in the 50 that were higher than some in the 30, so there does not seem to be a dose response as it relates dystrophin production. There does appear to be a duration impact.

We know that we did not see dystrophin at 12 weeks. We saw it at meaningful levels at 24 weeks. We see more dystrophin at 48 weeks than we see in the 24-week crossover cohort now, and definitely more than we saw in the original 24-week cohort. We also know that we are seen increased dystrophin production with continued dosing as evidenced by the 30 milligram patients, where each patient increased 28 to 31 additional dystrophin positive fibers between weeks 24 and 48, so I think we'll continue to look at the clinical outcome, but based on the dystrophin data now, we would conclude that we don't see meaningful or a statistical difference between 30 milligrams and 50 milligrams per week.

Unidentified Analyst

And, in the study you mentioned that the study is continuing, all the patients are continuing to receive drug were going to be checking on these endpoints every 12 weeks. Correct me if I am wrong. For how long will this continue happening, and will everyone switch to the 50 milligram dosing schedule or will you be maintaining the 50 and the 30 going forward?

Chris Garabedian

No. At this point, we don't have any plans to change the dose in these patients moving forward. Again, although the 50 milligram is performing better on 6-minute walk the dystrophin data is what we were looking to guide us and the fact that we did not see. For example, if we saw that 50 milligrams were producing 50% dystrophin positive fibers and 30 milligrams were at 20%, I think that would have made us possibly consider a dose escalation.

The fact that 30 milligram showed higher dystrophin levels at 48 weeks, but not higher than 50 milligrams at 24 weeks, that leads us to believe we don't yet know what the right dose is. We are going to be looking at the data further to see other clues of an optimal dose, but at this time we are not ready to conclude. Honestly, even if we went with the 30 milligram moving forward for registrational approval, it's always good to get additional safety data at a higher dose, because if we don't see a clinical response in a patient the ability to dose escalate if 30 milligram isn't you producing the clinical benefit is always a nice thing as well. Again, it's premature to speculate how the dose will be defined moving forward.

Unidentified Analyst

And, will we be seeing 60-week data and then 72-week data going forward or will this be more internal and the results this is essentially the end of the study, those will all be more in a compassionate basis and used for your safety database with discussions with the FDA?

Chris Garabedian

Honestly I think the safety information is the most important of continued exposure, especially as we go into the FDA and talk about early approval. The notion that we would have beyond two years of safety in these patients or in many these patients you by mid-next year, I think is very encouraging in terms of the safety profile, but we are capturing the 6-minute walk test on an ongoing basis every 12 weeks.

We have not guided on timing or if we'll be sharing that, but we will be analyzing that and I we will decide based on medical conferences where we could present those data and if it warrants an independent press release, but generally we like to share data at medical conferences and we will look for the timing of those medical conferences as they coincide with the additional 6-minute walk data.

Unidentified Analyst

And just one final question. Your phone ringing off the hooks. Even at the 36-week data, I can imagine even more the 48-week data regarding potential partnerships and other big biotech or big pharma companies wanting to get in or continue to expand in the orphan drug space. Can you talk to us a little bit about I know you've guided in the past that this is potential program that you would like to partner. What are your thoughts regarding partnership now based on this data. Has it changed? And is it something that we can expect in the near-term?

Chris Garabedian

Yes. I would say my comments about partnership following the 36-week data haven't changed. That is we have had a lot of interest expressed from kind of the usual suspects in the rare disease and neuromuscular areas. We knew that this was important data set that they wanted to see that we want to see. To better inform that, we deferred a lot of the in-depth conversations around partnership until we had data set and we expect that we will engage now and understand how a partner views the value of this program.

I think we have our options ahead of us whether to go alone or whether to consider an ex-U.S. or ex-North American partnership for the broader DMD program. We have many other exon skipping drugs that can come behind this that we believe this data set is highly reproducible against these other exon target. If a partner can bring the economics that would allow us to accelerate the broader program and to create a true win-win, where you we can get access to those drug sooner in the U.S. they can get access to those drug approved them more rapidly outside of the U.S., I think there is a structure that we would consider if the economics are right, and so we look forward to engaging our potential partners about you structure like that.

Unidentified Analyst

Terrific. Thanks very much and congratulations again.

Chris Garabedian

All right. I just wanted to conclude with some comments about the 6-minute walk test data, I had prepared in case the question came up, but I thought I'd use the opportunity now. There has been a lot of interest in anticipating how the two cohorts that we shared at 36 weeks, the 50 milligram and the placebo cohorts would perform on the 6-minute walk test between 36 weeks and 48 weeks, so I'd like to give some additional color around what occurred between these time points.

In the placebo delayed treatment group, we expected that these patients would have started to see meaningful dystrophin levels between 36 and 48 week time point as they now have been on eteplirsen for 24 weeks, and we have evidence that these patients, as I described earlier have high levels of dystrophin above 30% now at the 48-week time point.

Many were speculating that the best outcome would be to see a stabilization in these patients, and I am pleased to report that's what we've observed. Three of the four placebo delayed treatment patients were stable which were defining as less than 10 meter change either positive or negative from 36 weeks. One patient showed an increase in his 6-minute walk distance and he happened to have had the highest dystrophin levels 55% positive fibers at 48-week of all of the placebo delayed treatment patient.

Of the 50 milligram per kilogram eteplirsen patients, all of the patient saw an increase in their 6-minute walk test distance from 36 weeks and three of the four showed improvement, which we are defining as more than 10 meter increase in meters walked from the 36 week time point.

So, I want to provide that additional color, because there was a lot of interest about what happened to the patient between weeks 36 and weeks 48, so we are out of time. I just want to say we are very excited about this. We appreciate all the support that the company has had leading up to this, and we are excited to put this data into briefing documents and prepare for our FDA meeting moving forward, so thank you all for participating in the call this morning and thank you operator. That should conclude our call.

Operator

Thank you for your participation in today's conference. This concludes the presentation. You may now disconnect. Good day.

Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.

THE INFORMATION CONTAINED HERE IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL, CONFERENCE PRESENTATION OR OTHER AUDIO PRESENTATION, AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE AUDIO PRESENTATIONS. IN NO WAY DOES SEEKING ALPHA ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S AUDIO PRESENTATION ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS.

If you have any additional questions about our online transcripts, please contact us at: transcripts@seekingalpha.com. Thank you!

Source: Sarepta Therapeutics' CEO Discusses 48-Week Results From the Phase IIb DMD Study (Transcript)
This Transcript
All Transcripts