Pretty simple - with the ignorance and flakiness that the FDA has demonstrated in dealing with the prospects of an accelerated approval for Etep, the short thesis has taken hold. In a nutshell, the shorts believe the FDA will never approve a drug based on a trial with only 12 patients (because they don't understand the AA regs for rare diseases) or they believe that if Etep really worked, the boys would show improvement on their 6MWT performance, rather than a slower rate of decline (because they don't understand the disease and how Etep cannot reverse muscle that has already been destroyed by the disease). If you listen to the clinical experts and parents, who know that Etep is providing benefit; or believe the company's representations that their measurements of dystrophin reflect robust and consistent levels of dsytrophin production, when there was none before treatment; and you believe the FDA will actually follow the mandate given to them by congress with the AA regs, then SRPT is a bargain. Given the FDA's history to-date, however, there is still a good chance they will delay approval further and Etep won't be approved until 2017+.
The analyst question that struck me was whether the unblinded retinal scans from the isonep trial were reflecting any kind of general benefit. I thought that any and all data was kept from the company until it was unblinded, but the LPTN scientist seemed to indicate that they have access to the scans, but they have no data on which of the four pools of patients they are from, so he was not going to provide any speculation on expected overall benefit. My recollection is that the earlier trials showed "efficacy" in the form of reduced lesions/scarring, inflamation and "leakiness", but I can't recall if that simply halted the progression of the disease or resulted in better visual acuity, which is the primary endpoint in the current trial. They kept referring to "5 lines" mean improvement in the reading chart, which seems pretty dramatic - you would think just preventing further deterioration would be enough?
I didn't pay much attention to the asonep trial when I got into the stock a couple years ago, thinking that isonep would play out before asonep. When you are dealing with "last line" patients, most trials will be doomed from a median response perspective, unless you have a miracle drug - when the anticipated median progression free survival is less than two months, it is even more unlikely - the patients aren't healthy enough and there is not enough time for a drug to really show benefit. So, maybe they get some company or investigator to take a run with asonep in an earlier setting or they find some genetic/diagnostic marker that leads to a greater percentage of responders, but it most likely will be part of the biotech scrap heap. It is just painful to watch a stock get carved up when the reason you bought it is still months away from being revealed.
john j - listen the June presentation - the CEO was very explicit about how they could not issue any kind of PR about the trial or data without Pfizer approving it - that is part of the option agreement - and that they expected to have the unblinded data in hand by year-end, but would not be able to communicate anything until Q1. Get your facts straight!
I was mistaken about who is in control of the trial but the point is still valid - the June 2014 update call (just listened to again) indicated that they expected the data to be unblinded before year-end, but they had to wait for Pfizer and "their careful attorneys" to work through the data and how any press release would be worded, which they expected would be a couple of months, so both LPTN and Pfizer have likely been sitting on the data for at least a month.
There is an obvious natural history to this disease and the patient pool is from those that are not initially responding to standard of care (luventis, etc.), so there could be a positive buzz coming from the clinicians about seeing unusually positive results and/or Pfizer could have been sitting on the results for the past couple of weeks - it is not "material" information to their shareholders, so they had no duty to announce anything?
The only thing giving me hope is that there has been a substantial increase in volume tied to the recent share price increase and given that the pending trial results are through a trial under Pfizer's control, so there are likely numerous people within that organization that have a hint of the results, which could easily have been leaked recently. The fact that Pfizer chose to hold on to this program, while they were divesting all their other ophthalmology assets is a sign that they thought the pending trial results would be worth holding on for?
All these price targets have some level of discount applied to them for the risk of regulatory rejection/delay, so upon approval of Migalistat, FOLD is a $20+ stock. From there, their ERT formulations for Fabry and Pompe will double the value over the next 2-3 years. IOW, the ride has just begun - hang on for greater reward.
jk - an analyst price target is typically a 1-year outlook, so he obviously believes that Etep will secure AA - if it does, $45 will be cheap - you are clueless!
ru - way to step up and mis-state the situation again. SRPT never tried to correlate dystrophin levels with clinical results. In fact, when the analysts tried to press them on the idea that they should be able to correlate X% dystrophin positive fibers with Y% change in 6MWT, CG ran through a host of reasons why the correlation would not exist and any attempt to do so would cloud the picture. Pushing the idea of "refined" data on a rare disease with an endpoint as messy as 6MWT is just ridiculous - it is stunted thinking like that that has held up the approval process - maybe you should work for the FDA?
The only rational part of your latest rant is when you admit you have "no clue". When you say the FDA has a problem with dystrophin as a "marker", you have to distinguish between the validity of the marker and the validity of the measurement - it is clear the FDA has issues with how dystrophin is measured (IMO because they don't understand it), which is the focus of this panel, but not dystrophin's validity as a marker. The only hope of DMD drugs being developed for the lesser populated exons is if they resolve this measurement issue.
In the end, there are more measurement issues inherent in the 6MWT than there are with dystrophin measurement and the idea that BMRN has a drug that is by therapeutic design supposed to produce dystrophin and part of their strategy is to discount the importance of measuring dystrophin is clueless.
johnny - does that mean you are on board now, too - you said you weren't impressed with the CC. I'll admit it wasn't anything to get the juices flowing and waiting another quarter to get any real data on how the launch of Omidria will go is frustrating, but there were positive comments/vibes for much of the pipeline. I think this is one you keep for the long haul, rather than bail out on any positive Omidria traction. Something tells me the value of the rest of the pipeline will eclipse Omidria's value by multiples?
likeafox - I'm struggling with the concept of "rescued", but given the nature of the disease, there is no doubt that muscle tissue is destroyed little-by-little and that at some point it becomes irreversibly damaged. It is hard to imagine any of their diseased muscle tissue is truly healthy, so the idea that Etep can improve the health of all but the tissue that is past the point of rescue is a valid one. Your idea that fatty infiltration and scarring being more advanced in the legs also seems rational, given the burden the leg muscles incur with simple walking vs the rest of the body.
As I stated before, I believe the deterioration of the 6MWT scores is not so much of a story of limited effectiveness of Etep, but more the inability of the remaining healthy leg muscle tissue to keep up with the increasing height and weight burdens of these growing boys. I would bet that just like Christine McSherry, all the parents have seen subtle improvements in the muscle function of their boys outside of their ability to walk. The FDA is supposed to take these "patient reported outcomes" into account as part of the approval process for rare, deadly diseases, but so far they have shown no signs of doing anything but getting caught up in the complications presented by the clinical data.
Another fantasy post - if only big pharma was involved, blah, blah, blah. Yeah, it would have made a world of difference for a company that was not familiar with SRPT's PMO technology and/or DMD to be "educating" the FDA grunts, who have proven that they have absolutely no clue about the disease, dystrophin measurement, etc., etc.
I think it is more than "interesting" - Jett is in college, so hasn't used a pencil in 4+ years and after 4 months on Etep he suddenly feels like writing again? I'm sure it will be viewed as just another placebo effect by the twits at the FDA - they probably believe that if he doesn't get out of the chair, the drug isn't working.
You could tell there was a lot of analyst support on the call - many softball questions. No doubt, the launch has dragged out beyond my expectations, but there is something to be said for their strategy. The purpose of the pre-launch was to make sure the reimbursement systems were in place and working seamlessly, so that when new docs start ordering Omidria, there are no annoying complications - when you are dealing with a $500 product that theoretically can be substituted with a cheaper, compounded product, any problems with getting paid may turn off potential new docs indefinitely.
One of the softball questions that was interesting is the fact that the cost of the compounded product comes out of the doctors pocket, while they will get reimbursed in full plus a handling charge for using Omidria, so this is a money maker for the docs - the per procedure numbers are not huge, but if you are doing hundreds of procedures a year, it can add up to some meaningful dollars?
The flip side of his twisted conclusion that the non-responders declined more rapidly than normal is that the responder group reflected a natural slope/path to their disease progression. The clinicians are stating that the stability reflected in the responder group is not normal - it is an encouraging sign that the treatment works. Who should you believe, the clinicians that work with ALS patients every day or a hack "analyst" who tweets as much about his passion for drinking as he does about biotech stocks?
I have some shares I purchased in an IRA about 3 years ago and haven't paid much attention. I know it is a good growth story, but it is trading 100+X next years EPS - does the future growth support that?
If the "responder" group supposedly had greater arm and leg strength going into the study, then why are their baseline ALSFRS scores comparable to the non-responder group?