How confident are you in the 3.0 median OS for the control arm - is that well established in a number of trials? I've seen a number of studies that were delayed on readouts that ended up being control arm variation (the latest being Vical's failed melanoma vaccine), but my sense is that this is something different, simply because there is not a lot of variability in 2nd line pancreatic outcomes and the delay of a 3+ months in this case would translate into a 100% increase in median OS in the control group, which is unlikely. I think at worst, the results will be positive, but don't knock the ball out of the park on statistical significance?
The only way to "expedite" the other exons is to design a confirmatory trial in Exon 51 that has a valid/agreed-upon surrogate measurement that can be taken into future trials. Only the Exon 51 numbers are large enough to establish a meaningful connection between whatever surrogate measure they decide upon and the resulting clinical benefit that will be observed over 48+ weeks. The confirmatory trial won't be completed until late next year, so the earliest a "surrogate-only" clinical path can be established for the other Exons is probably not until early 2016. That is probably consistent with the timing of when some of these other exon drugs from SRPT will be ready for the clinic?
Just reiterating the same goals they have had since last November - get the sign-off on a Phase III/confirmatory trial design and get that started as soon as possible and then work on reversing the FDA's decision on AA. Whether AA is in the cards, they need the Phase III trial to get moving.
Exactly right - in the absence of real buyers, the shorts control the market. With institutions seemingly sitting on the sidelines when it comes to biotech stocks these days (low volumes everywhere), the shorts are hammering the retail and momentum traders into submission, many not having a choice due to margin calls. Most of my holdings are trading at less than 50% of the analysts' targets - patience will be rewarded here.
RBC Capital just put a $31 price target on the stock last week and that didn't seem to help?
As another poster mentioned earlier, CG indicated that they would communicate any material changes in FDA guidance when they had confirmed meeting minutes. Theoretically, it is hard to imagine the guidance the FDA provided them back in Nov could materially change for the worse - at that time a placebo-controlled study (with Exon 51 boys in the placebo arm) with a mixed bag of clinical measurements (the FDA was doubting the validity of the 6MWT as the primary endpoint) and no identified valid dystrophin measurements as a supporting endpoint was the guidance in place. How can it get any worse than that? In some twisted way, the fact that the FDA cannot come to terms on what a pivotal trial should look like may force them to accept an AA - ultimately, time is the most important driver of evidence for clinical benefit (the longer the boys are stable, the more definite the clinical benefit is), so if the FDA is doubting a 48-week trial is enough time to provide that definitive evidence, then it may be more likely that the accept AA from a moral perspective - i.e. their doubts should not leave kids and families suffering.
It's not about being funny - it is about being realistic. As ridiculous as the pricing is on a lot of these drugs for rare diseases, companies like SRPT would not exist without the "system" behind it to pay for the drugs they invent. The idea that the company could survive producing a non-approved drug for families that could not pay for it is "hilarious"!
The reality is that the FDA always had the "cover" of waiting until mid-late 2014 in order to make a decision, because SRPT needed that time to get the manufacturing in place and get the Phase III started. The time they have wasted by telling the company not to file for AA is that if they change their mind, SRPT is now 3+ months behind in getting the filing prepared.
What a loser post - "SRPT should stop the shenanigans and get busy with the P3 trial design" - what do you think they have been pushing the FDA to make a decision on since Nov? The only thing dumber than your post would be for the company to start the P3 without getting sign-off from the FDA on endpoints, control group, etc. The idea that the delay in the clinical process has anything to do with SRPT is absurd - they have provided the FDA everything they have asked for and more on a timely basis - it is the FDA that is dragging the process out.
jrrt - Just read the article - it confirms what was discussed on this board before regarding the failure of the Drisa trial does not show a disconnect between dystrophin production and clinical benefit, because Drisa's dystrophin measures were weak and inconsistent. With respect to whether Etep can achieve this magical 10% threshold as measured via Western Blot, he bases his conclusion on "one sample", while casually acknowledging that given the preclinical studies, it is not surprising that Etep showed dystrophin production via Western Blot, while Drisa did not. Regardless of whether Etep generated 10%+ levels in any of the boys in the current study, that does not mean the clinical efficacy data should be dismissed. Longer term follow up on the Phase II boys (possibly even another biopsy down the road) may show the 10% level is achieved over time or future studies may show you need to increase the dosage to get to a 10% level. There are so many things to learn about the use of Etep that will take decades of research, but the idea is that until you have all the answers, it should be kept off the market is idiotic.
Wrong - all the boys in the study showed at least 20% dystrophin at 48 weeks. Who is this Lu and where are you getting this quote?
endo - My code had two letters followed by two numbers and a final letter, which was "o", which I didn't notice until I tried to input it as a zero - whoever devised that was stupid. I was at work while listening, so didn't hear every word, but didn't catch anything game-changing. I think from here on out I think it is going to be a question of quarterly revenue performance - my hope is that the 40% growth they are targeting for 2014 is conservative and 50-60% growth will drive the share price back into the $20's as the year unfolds?
With the FDA touting how "flexible" they are in getting this treatment to market, any Phase III requirement that drags the enrollment process out or takes more than 12 months of testing for efficacy will be a joke, unless they grant AA as part of that requirement. They know they already look like a joke, so you have to believe they don't want to make it worse.
That is not an option - the drugs for the other Exons aren't yet in the clinic, so a Phase III on any new Exons would be over a year out and there aren't enough boys in the other Exon categories to do a meaningful Phase-III trial - that is why they are pushing to get "class approval" based on Exon 51 efficacy and surrogate measures.
You are correct - Tubulysin will end up being worth multiples of Vintafolide and they will have early clinical data by later this year. Once the FDA gets comfortable with their receptor and linker technology, it is off to the races - over $100 by the end of 2015, IMO.
ml - a Phase III trial was always a given - the question was whether it would be a confirmatory trial or not and what the trial design would be. Even if under some miracle the FDA (having reviewed most, if not all, available data on Etep concluded that they could grant full approval based on the Phase II trial, I think SRPT needs the Phase III trial in order to generate the biopsy data that will allow future Exons to approved based on pure surrogate measures, because there won't be enough boys to do an efficacy trial in a short period of time.
A placebo arm of non-Exon 51 boys is essentially a comparison against NH, with possibly a better-targeted patient group in terms of age and baseline 6MWT. The complication is that there probably aren't enough NH studies to prove whether non-Exon 51 boys decline at the same rate as Exon 51 boys. Ultimately, the only rational and moral thing to do is grant AA and do a longer-term Phase III study (96+weeks). If you grant AA and try to have an Exon 51 placebo arm, you may have trouble recruiting, although if the Phase III trial does start in Q2 and Etep is not available outside the trial until Q4, that should not be an issue - at worst, the placebo arm would be treatment delayed, like the Phase II trial.
Who cares - there is nothing magical about April 8th - a conference that has been scheduled for months that has no bearing on the FDA proceedings or timeline. When the company has a confirmed path to approval for Etep from the FDA, they will announce it - trying to predict when that will happen is a meaningless exercise.
I didn't say they got into the stock when ICPT announced - they became aware of GALT when NASH was put on the radar because of ICPT - look at the the heavy volume over the last week since they announced this mornings presentation - many of those buyers over the last week were looking for a home run and when it didn't materialize, they are selling and moving on to the next shiny object.
The price dropped because there were a lot of short-term traders attracted to the stock in the wake of the ICPT explosion, where the price went from $70 to over $400 on their Phase II NASH results. These "investors" will not hang around beyond a day or so, resulting in many of them bailing out when there were no large buyers coming in today. Once the short-term profit-seekers move on, it will be up to the analysts or institutional players to make difference in the stock, or else you will have to wait until the 2nd cohort results in Jul/Aug - while these results will again be in only 6 or so treated patients, if you see the dose-dependent results in the same biomarkers with no safety issues, the picture will begin to take shape and by the time they get into a Phase II trial by year-end 2014, the stock should be creeping toward that $1B market cap range (~$40 per share).