I bought into this company last summer but then bailed with a small loss in October when the biotech sector was getting crushed and my really big holding was dropping enough to make me nervous about a margin call. Pure luck but I missed the meltdown to 12 dollars as a result. Since then have been buying back in average price about 18 dollars at this point. This is what I see as a physician, and I have read the Annals of Neurology article in its entirety.
Eteplirsen has a convincing mechanism of action. The production of a truncated dystrophin protein converts the DMD patient into the equivalent of a Becker's MD patient, Becker's patients produce a truncated dystrophin also. Becker's patients have lifelong weakness but do not lose mobility or end up on ventilators in their teens. In the muscle biopsies we see consistent production of significant amounts of truncated dystrophin in all 12 boys. We also see over 2 years of muscle strength stability, which is completely the opposite of the natural history of DMD. Given this, it is highly likely that eteplirsen is an effective therapy for DMD. If my child had it, I would demand it right away. There is no toxicity out to 2 years.
The FDA is uncertain what to do. To approve a very expensive drug for use on children based on 12 patients would be highly unusual to say the least. They do have the legal authority through AA, but this is a real stretch and there is no historical precedent for this. The FDA by its nature is extremely cautious. No one wants a repeat of Vioxx or thalidomide.
On the flip side, the desperate and immediate need of these children is obvious and overwhelming. For them, a delay of 6 months not to say 3 years is huge. Some of these kids will die while the FDA makes up its mind. The parental and political pressure will be huge. How the FDA's conservative nature and this parental pressure resolve itself is anyone's guess. Continued...
Appreciate the effort, but not sure how you can even mention Vioxx as some kind of legitimate analogy on why the FDA would be warranted in being cautious with Etep - Vioxx was a chronic pain medication that showed potential heart issues after long-term, high dosage use. Putting aside the fact that Etep has a pristine safety profile so far, what potential side effect can you envision that could possibly be worse than the disease? The parents have voiced their willingness to accept almost any potential risk, because they know just that - nothing can be worse than the disease. Given the safety record to date and all the preclinical data showing that Etep's PMO delivery agent can be dosed at huge doses with no side effects, safety shouldn't be more than an easy check mark in the decision on whether to grant AA. Also, as the company has pointed out, there are number of drugs that have been given AA based on trials of similar size (and much shorter duration) than the Etep Phase II trial.
There are three possible outcomes.
The best for us and for the families is AA in the next 30-60 days. Such an outcome would send the stock over 100. For SRPT, this would be just the start. They would move on the develop exon skippers for most of the other DMD kids, and then use exon skipping technology in a variety of diseases and even infections to create a broad pipeline of new products. Eteplirsen is just the appetizer. In this scenario the FDA would want the company to essentially conduct a P4 trial with drug on market to prove that it works, if it fails to live up to its billing, the FDA could pull the plug on it (see Xigris).
The worst outcome would be the FDA requiring a full P3 trial with at least 18 months if not 2 years of follow up. That would take probably 6-9 months to set up and create an SPA with the FDA, and another 2-3 years to run. We would get data in 2016 or 2017. Such an event would probably knock the stock price back into the teens but would be a buying opportunity for those with a 3 year investment horizon.
The third, and I think most likely outcome, is that the FDA will ask for an additional limited trial looking at dystrophin production at 6 months and 6MWT stability at 1 year. This could be done by end of 2015. Such an outcome would not knock the stock price back much, might even hold steady.
Perfect posts, stockdoc. Agree on all points. One other possibility I see is the FDA allwoing a Phase 3 set-up they way Chris wants it pretty much. At the same time, they suggest that we may as well go ahead and prepare to file for the NDA. They also note that by the time the NDA application is in their hands and they have been able to look at 3 months of safety data from the Phase 3 (this may be July or August) that they may then be in a better position to possibly grant an 'accellerated approval" if all is looking good. This is actually the most reasonable course for all concerned - FDA, Sarepta and the DMD community. Thus I believe it will be the upshot of the current talks. It's initial effect on the stock price will be modestly possitive. Only because that's the way it goes around here. But it will be a slow climb to a climax at the moment "approval" is granted - probably late September or so.
If scenario #2 was to happen there would be a “riot” equivalent to the “1992 California Riot “. This is Democracy. If that was to happen, the federal government would step in and investigate the FDA. High ranking heads would be rolling in the FDA for corruption and abusing of the system. If I was to head the FDA I would think twice about going down Aisle #2. I am not going to lose my job and possibly be prosecuted for defending some hard heads within the neurology department.
Actually, a limited P3 would cause a nice jump up in stock price I believe, but it goes without saying, this decision would be a crushing blow to kids currently on the fringe of losing physical abilities, or death. I just don't see how other drugs for non life threatening diseases warrant AA, but this remarkable drug doesn't. The data is compelling.