grey - I think the point of the statement is that they were not going to start the trial until they get the FDA to sign off on the endpoints. Given the FDA's flakiness in dealing with both dystrophin and 6MWT measures, it would be too risky to start a trial until they signed off on the endpoints.
kay - you may have raised a legitimate comparison to the efficacy demonstrated in Prosensa's 2b trial, but when when you say "nothing is tracked" when it comes to safety in the SRPT's trial, you just portray what a moron you are. All the liver tests that Prosensa failed are part of SRPT's trial - to say otherwise is just idiotic.
Not sure if SRPT provided individual 6MWT figures at baseline, but the averages for the different cohorts are in their presentation slides - for the treatment group, the average was ~366 meters and then the average for the placebo delayed group at wk36 was 328 meters. They also provide a range for all 12 with the lowest being 259 meters and the highest being 437.
I've commented on the fact that the parents of boys that have lost the majority of their physical capacity will have a tough time deciding whether to treat their boys, but are you saying someone like Austin McNary, who has been in wheelchair for several years and is now losing the ability to use his arms shouldn't get the drug? Maybe 10%-15% of the boys are past the point where treatment might be hopeless, but for the remaining population, you have to be kidding if you think the "penetration" within the first year is less than 90% - unless there are insurance/payment issues, what parent or doctor is going to say no to this drug?
The "subset of treatable age ranges"? Where do you come up with that - what doctor or parent is going to determine that their boy is too young or old to be getting the one treatment that could benefit them?
She is such a dim bulb, I'm surprised anybody pays attention to her. She has made it clear that they are not going to hike rates until the labor market is fully recovered (not just the unemployment rate, but some sustainable wage inflation) and that is not going to happen for several years, if ever? Not that I believe analyst price targets are any more meaningful, but the majority of my biotech holdings are trading at less than half of what the analysts' median price target is, so how much overvalued can the small cap biotech market be?
What's your point - everybody already knew these stats. The existing population of exon 51 boys in the US was estimated in the 1,500+ range , so assuming Etep helps these boys live longer, the market should slowly grow from 1,500. At the bottom end of the pricing range, Etep would generate 1,500 X $200,000 = $300M annually beginning next year. The remaining exons in SRPT's portfolio would push revenue to over $500M within another 5 years. Are you saying the current share price over-values that revenue opportunity?
The key to a 4th biopsy would be if it is done in accordance with whatever protocol the FDA has deemed appropriate for the upcoming Phase III trial. The FDA has done a lot of hand wringing over dystrophin measurement (what the best test is, how the muscle is sampled, how the labwork is done, etc.), but it is not yet clear whether they have decided the Phase II dystrophin data from the Etep boys is lacking in some manner. A 4th biopsy that showed consistent or improved dystrophin measures (vs 48 weeks) would help prove the durability of the treatment effect and may help interpret the 6MWT and pulmonary data.
fox - this is the point I have been trying to make the last couple of days - is the decline in 6MWT the result of continued muscle deterioration (implying Etep is not working) or is it the inability of the remaining healthy muscle tissue to keep up with the height and weight increases as they age. I can't imagine any trial being able to conclusively answer that issue. If you only enroll boys that already have substantial damage to their muscles, you will never know what is driving their progress over 2-3 years. The only way to know if Etep will provide long-term benefit is to start treating boys as early as possible and see how they progress, but that could be a 7-10 year trial issue. Better to get the drug approved, provide it to as many boys as possible and do as much post-approval study as possible.
Appreciate the sentiment, but not sure why you think we will see a spike towards the end of the year - filing the NDA won't be noteworthy and I can't imagine anything out of the WMS presentation that is going to change the minds of the naysayers. It is my firm belief that Etep and its clinical path is completely misunderstood by a good chunk of the investment community - they either believe (like pasteur) that the data from a 12-patient extension study is not sufficient to for approval or that if Etep really worked that the boys would be improving, as opposed to struggling to maintain stability. IOW people don't understand the AA process or DMD natural history (particularly as it relates to boys in the 7+ age group). I expect that the only thing that is going to convince these naysayers is when the advisory committee experts set them straight and give the FDA no choice but to grant AA, and that won't happen until mid-2015. Maybe if you get a 4th biopsy and/or there is some individual detail in the 144 week data that provides some nuance to the overall story you could see some recovery by the end of the year, but the Etep story will more likely play out in 2015. The wild card will be some groundbreaking pre-clinical data and/or a lucrative venture deal in some indication that hasn't been announced, yet.
jkad - I think it is clear that deterioration begins as soon as they are born - it just doesn't become recognizable until they are diagnosed at age 4-5. The more I think about this, the more I believe that there is a constant struggle going on between remaining functional muscle and the demands placed on that muscle from these boys continuing to grow, until at age 7+ function starts to deteriorate at a greater and greater pace. The fact that Etep has seemingly stalled/delayed their deterioration at a point where they should be rapidly declining due to substantial accumulated damage is very meaningful and not to be dismissed, even if these boys should continue to slide.
I guess when you boil it down, there are three potential scenarios at work with the declines experienced by the boys at w144 - (1) Etep has had absolutely no impact on the boys muscles and they continue to deteriorate, but due to the odds of enrollment and the natural variability in the population, two lost ambulation immediately, 6 on treatment showed stability for 120 weeks and then started to deteriorate and 4 placebo-delayed started to deteriorate then stabilized for 72 weeks and then started to deteriorate (2) Etep has had some impact on their muscles and has slowed the deterioration of their muscle function or (3) Etep has stopped the deterioration of their muscles, leading to an initial stabilization, but the salvaged muscle mass in their legs is not enough to stabilized them as they age and add weight and height. IMO, scenario one makes no sense - Etep is having some effect and between scenario 2 & 3 it is a toss up. The individual data would help make sense of this - if there are some boys that have in fact improved at w144, that goes a long way toward making the case that the drug is working and the variability is due to the existing muscle damage at the time of enrollment.
bb - The dosage is automatically upped as the kids grow - they are dosed based on their weight. The key point in the equation is once the muscle tissue is destroyed by the disease it cannot be recovered. The company is caught in this paradigm of trying to prove the drug works on patients that are already damaged from the disease, because testing it on younger boys would take too long to show a benefits - if you tested it on 5-6 year olds you would have a 5-7 year trial to prove no deterioration in their 6MWT. Testing it on 7-9 year olds shortens the equation but brings in the risk of having patients with too much damage (the twins) or if the damage is stopped, may not have enough functioning muscle mass to be stable as they grow.
winter - that is the point at issue - are the increasing "rates of decline" in the 6MWT evidence that Etep is only slowing progression in the deterioration of their muscles or is a case of the boys remaining leg muscles that are being maintained by Etep are not healthy enough to carry the load as the boys age and gain height and weight? There is probably no way of answering that question conclusively and the only way to know whether starting treatment earlier will salvage enough healthy muscle to get them through to adulthood with no significant loss of function is to actually get the drug approved and start treating boys as early as possible.
All these comments throwing Etep's ability to "cure" into the trash are way off base. If the twins that lost ambulation end up living into their 50's with no severe deterioration of their lungs, heart, arms, etc. going forward, would that be considered a "cure". Nothing is going to be able to restore the muscle that has been lost to this disease, so every boy's "cure" is going to be relative to how much damage has been done before they start treatment. For some, it will be confined to a wheelchair, for some it may be using a walker as they age and hopefully for those that start treatment early it will be walking to their grave at ripe old age. The less obvious and cruel potential "cure" will be for the boys that have lost most of their physical functions, where treating them with Etep may simply drag out the suffering they endure to the end - what would you do as a parent?
Dosage already is varied by body weight - the 30mg and 50 mg dosages used in the trial are per kg of body weight.
CG commented on that in the past - the twins were by far the tallest boys in the trial and height is one of the predictors in determining how quickly DMD boys lose ambulation - their deteriorating muscles can't keep up with weight and leverage of their growing limbs. That is playing out more slowly with the rest of the Etep boys - how much muscle was saved, how will the muscle grow in relation to their bones, etc.
The Becker's comparison is missing the point in this case. CG has spoken many times on the hope that Etep will convert exon51 boys into the milder Beckers form of DMD, but that would be when the boy starts on Etep before significant muscle damage has already taken place - that is not the case here. What drove the twins to lose ambulation and what will ultimately determine the long-term prospects for the remaining 10 boys on Etep is how much healthy muscle tissue remains that can be salvaged by Etep and how will that muscle tissue grow/perform as the boys age. The prospect of converting boys into Beckers patients can only be tested by starting them well before age 7 and tracking their progress into their late teens - a 15 year trial is not realistic, so the only way to realize the Beckers hope is to get Etep approved and get boys on the drug as soon as possible.
If everything you said was true, then the FDA would not have told SRPT to file for AA or have given them alternative paths to approval. Are we to believe the FDA is going to take them all the way to the goal line and then say, "the data over 168 weeks is very compelling and the experts all agree that the drug is effective, but if we include the twins, then statistical significance for the original 48 week data is lost, so sorry"? You have a mental block here - take a pill or something, but give it a rest, already!
pasteur - you're like a rabid dog that won't let go of a bone - we get it already - everybody knows, the twins lost ambulation and their 6MWT results are excluded from the results. As the FDA has communicated to the company, they will supposedly be acting in good faith with the AA regs and be as flexible as possible in analyzing the available data. Everybody but you seems to understand that Etep will not restore lost muscle function, so when you are enrolling patients on the precipice of losing ambulation and it takes 12-24 weeks for meaningful levels of dystrophin to be produced, you run the risk that some boys will not be able to perform the 6MWT. Does that mean Etep is not working for them or that boys that have lost ambulation can't benefit from the drug? I'm not sure why, but don't seem to be able to grasp the AA regs and how they relate to the Etep clinical path.