Just to show how broken the market is, they last raised cash two years ago (Feb 2014), selling 6.325M shares at $18.95 per share for a total raise of $120M - the current enterprise value is around $120M. You can argue that the market was inflated when they sold the shares, but given the pipeline progress since then, it is hard to imagine the value cratering to where it is now.
I'm sure if there is a market for it, they will develop it. They have spoken to how flexible the technology is - it is just a question of prioritizing opportunities/investments.
They don't have more than 4 years of data on individual boys, they have 1-2 year graph lines on "all patients". Why they are including all patients in the figure is questionable - including graph lines on boys less than 7 we know is worthless and the figure is so clogged up with 1-2 year lines, you can't make any sense of it. If the FDA was trying to confuse the results of the Etep trial, mission accomplished.
Part of the problem is that BMRN played the game that all their data was valid and reasonable and the FDA blasted holes in all their analyses and BMRN did not have much of an argument to say otherwise, so the FDA's analysis and position seemed to be on target. They then come out blasting holes in SRPT's data, but much of their ammunition is speculation or downright faulty logic/analysis. You can't expect the "press" to take the time or have the intelligence to distinguish between the drugs, although the one guy from American City Business Journal seems to have made the effort - unfortunately, he seems to be the lone voice.
Where are the analysts in this game? When Drisa was trounced at the AdCom and the BMRN team had no pushback on the FDA's breakdown of their trial data, several analysts still said they had a chance of approval. SRPT and the parents have already pushed back on the FDA's faulty analysis before the AdCom, but most of the analysts are on the sidelines.
You're not a DMD parent - you are an idiotic tool - if you have been following the ETEP story from the beginning, you would know that SRPT's "path to approval" was dictated by the FDA and now that the data is at hand, the FDA is back-pedaling on its own guidelines. The idea of a perfectly designed and executed trial in the DMD space is a fantasy - there aren't enough patients and not enough precision in establishing baseline characteristics to generate controlled trials. That is one of the issues addressed by FDASIA - the ability to be flexible in assessing available evidence in the rare disease space. If you were a DMD parent, you would understand this and be providing support for the way SRPT has jumped through the ever-changing hoops the FDA has put in front of them. The fact that you would use dmd.parent as your alias proves what an #$%$ you are!
Read the interview of Jenn McNary - she flat out refutes the FDA's speculation on her boy receiving higher steroid doses and more intense physical therapy. Later on twitter she indicates she informally polled 10 of the other parents and they all said the same thing and that the FDA was not in contact with any of them about the level of their boys' steroid use or physical therapy - the FDA made up the whole thing to rationalize why the ambulation data might look better, because they don't believe the dystrophin production level is meaningful.
The dystrophin data is the crux of the issue here - Kunkel acknowledged that the amount being produced is small, but does that mean it is not clinically meaningful? The FDA claims that the levels of dystrophin according to the western blot test were within the range of what untreated DMD patients might produce, but if that is the case, why did BMRN not generate similar data from their DMD patients - their western blot levels were measurably absent or well below the levels generated by the Etep boys.
In the end, most of the FDA's assertions can be refuted and you will be left with somewhat positive clinical data, but from a small sample size that lends suspicion, and a whole slew of stories from the parents about how Etep has made profound differences in their boys lives - will that be enough to sway the AdCom?
The "idea" of a historically controlled trial came from the FDA - there aren't enough patients to enroll a meaningful placebo-controlled trial, because the baseline restrictions are too tight and ultimately anyone who realizes they are in the placebo group will simply drop out midway through the trial - you can't expect parents to keep their kids on a weekly IV infusion, blood testing and multiple muscle biopsy tests when they are getting a placebo - it is unethical from so many angles. The FDA has distorted the comparability of the historical control group to come to the conclusion that the boys progress is consistent with natural history - 10 of 12 boys on Sarepta are still walking after 4 years, vs 2 out of 13 of the historical control group - how do you conclude that is the same performance? It is difficult to imagine what agenda the FDA is following here and perhaps that has been the longs biggest mistake - trusting that the FDA would act in a reasonable manner and consistent with the spirt of the AA regulations.
nerd - My thoughts exactly - the FDA looked for reasons why the data might not make sense, instead of discussing the rationalization of why the data could be meaningful. Two examples stuck out in my mind - they noted that the four 50mg patients did not show dystrophin production in the week 12 biopsy, whereas the four 30mg patients showed increased levels at 24 weeks - their conclusion was not to question whether SRPT's assessment that it takes time for dystrophin levels to be generated was reasonable, but rather to dismiss the 24 week data as unreliable. The second was the assessment of the comparison of the historical control data - they surmised that higher use of steroids, physical therapy and aggressive management by the parents could account for the differences in the 6MWT scores, without having any clear evidence that was the case. Granted, their job is to be skeptical and to find flaws in the way the trials are conducted and clinical endpoints measured, but to speculate on reasons why the data should be questioned without having evidence to conclude one way or the other is not very scientific.
The primary reason to avoid speaking to the safety issue is that it impacts all their DMD drugs - the platform/backbone chemistry is the same, so if the safety profile is deemed to risky for Drisa/Exon 51, then it will be the same for all the other Exons. Ultimately, safety will be the death knell of their DMD platform - they can't safely dose at high enough exposures to induce measurable dystrophin production, so they will have to rely on clinical performance data that will be tainted by drop-outs, missed doses, and difficulty providing a valid control arm. As flexible as the EU is in approving drugs for rare diseases, they are careful about safety issues for chronic treatments. JJ points to PTCT as an example of the EU flexibility, but their drug's safety profile is pristine compared to Drisa, so they will likely find the risk-benefit analysis lacking, assuming BMRN can convince them there is any benefit. Odds are that BMRN's DMD program will be scrapped by this time next year.
or as IBD would characterize the data, "ambiguous, leaving approval highly uncertain". Another case of a reporter/analyst making a strong opinion, without providing an ounce of detail on how that conclusion was reached.
It's articles and analyst comments like this that are the reason SRPT gets no respect - the implication is that the only way it will get approved is because of political pressure. I have read very few articles or analyst comments that spoke to the efficacy and dystrophin production evidence - again, the implication being that the trial has only 12 participants, so regardless of the evidence, it can't be deemed significant or reliable. They don't even bother parsing out the evidence or analyze the approval in the context of the accelerated/conditional approval rules.
at market highs just 2 or 3 weeks back? The share price peaked in Sep and has been on a downward slide since then. I bought in around $16 expecting the recent hemophilia data to provide a lift, or at least support - no such luck - this biotech market is in the worst meltdown I have ever seen.
The only people that can view this as bad for SRPT are the ones who have a cursory knowledge of the two drugs and are caught in the ignorant assumption that the drugs are very similar. Anyone who understands the distinctions that allow Etep to be dosed at 5+times the does of Drisa, resulting in proven dystrophin production for Etep vs none for Drisa and the complete lack of AE's in the Etep trial vs significant AE's and dropouts/missed doses in the Drisa trial know this is completely false.
Is the CRL available somewhere - how do you know safety was not mentioned? Besides, if there is no evidence of efficacy, safety becomes a moot point - as the FDA stated in their review, no risk-benefit assessment was made, because there was no evidence of benefit. In the case of Etep the risk is minuscule and if you believe the testimony of the moms, the benefit is enormous - even though they all know and admit it is not a "cure".
A "small effectiveness study"? RNA/GSK did two small studies and one large study and none of them showed evidence of efficacy - what makes you think another small study would sway the FDA? Also, given the horrendous safety profile revealed during the AdCom review, what parent would put their child on Drisa?
bio - I certainly don't understand the nuances, but I recall CG saying that a filing is not designated by the company as seeking accelerated vs full approval, rather that is a decision the FDA can make based on the data presented, but in order to be eligible for AA, the company would have to have a confirmatory trial up and running. IMO, AA was not even an option for Drisa - if they were given conditional approval to market the drug, how would they ever be able to enroll a confirmatory trial?
jrrt1 - I think there are a number of stupid retail investors that think a CRL is a good thing - that it is not a complete rejection, but a delay that may require the company to just provide more data.
bio - How could Drisa be considered an AA case - they didn't meet the requirement of having a confirmatory trial in place to warrant an AA - beyond the fact that there was no evidence of efficacy, let alone a "reasonable likelihood" of clinical benefit.
JJ's comments on CNBC and the Sunday interview certainly gave that indication - he essentially wrote off the US market as not important and suggested that a FDA rejection was already priced into the stock - I guess that was wishful thinking?