I think the variability issue is something that a larger trial would eliminate or minimize. Besides that, as others pointed out, the dose used in this trial was half the dose being used in the other Phase II trial. The Phase IIb trial is targeted to enroll 200 patients, versus 38 in this current trial, so between the higher dosage and the larger population, the clinical outcomes should be cleaner.
My interpretation, which may not be correct, is that there were several plasma clinical endpoints - ammonia levels (absolute measure); reduction in ammonia levels (again, absolute) and relative reduction in ammonia (% change). Presumably, all patients were considered to have abnormally high ammonia levels at baseline and that they would theoretically be reduced to a more normal level after 12 to 24 hours. Given the high variability in the absolute levels, the difference between placebo and treated at the 12 or 24 hour mark was not statistically significant, even though there were marked differences in the absolute and relative reductions observed. So, for example, if someone in the treated group went from 10 to 5 (a 50% reduction), they were considered equivalent to a placebo patient who went from 6 to 5 in the absolute measurement endpoint.
A similar situation took place with FOLD last year, whereby a clinical endpoint did not take into account the variability at baseline, so even thought the absolute differences observed in the treated group were significantly higher, the trial was deemed a failure. When the dust settled and everyone figured out the drug was working, but the trail just had a poorly defined clinical endpoint, the stock quadrupled. Hopefully, that is the case here, as well.
The lack of statistical significance in a 38-patient trial (19 in each arm) is not unusual - if, as they indicate, the plasma ammonia readings were highly variable among patients, attaining SS with 38 patients is almost impossible. The fact that they did reach SS on urinary levels with such a small population is more reflective of the efficacy impact than the plasma readings.
What does "early efficacy responders" even mean? If there is any lesson to have been learned over the past 3years, it is that the 6MWT is a very flakey clinical endpoint - there are way too many variables at play, besides whether Etep is working - the two key variables being how much damage has already been done before treatment kicks in (impossible to measure accurately) and how quickly the boy is growing (easy to measure, but hard to interpolate how it will impact clinical measures). As has been discussed before, it will be decades before the ultimate clinical impact of Etep is understood - that, however, is not an excuse to withhold approval from boys that would benefit during that time.
Whatever - cg's implication (which you don't seem to dispute) is that the company is screwing up and causing these delays - his post was intended to mislead. There has been a lot of bashing on this board about how CG has screwed things up trying to steamroll the FDA for an AA with the Phase II data and how if only we had a CEO that knew how to manage the FDA process, we would be that much closer to approval. The reality is that CG has treated the FDA with kid gloves and been whipsawed by their capricious decisions and any delays in the approval timeline have been caused by FDA misunderstandings and new/changing directives. This delay in the trial for younger boys is just another example of the FDA's "excessive" behavior. Why anyone would be shocked or surprised at this stage is beyond me.
fired - you "agree with little cg"? His whole post was centered around the idea that SRPT's confirmatory trial is a year behind schedule and therefore RNA has a leg up on SRPT in getting new data to the FDA - everything about his post is false, but you agree with him? If my memory serves me correctly, last quarter CG said they were ahead of schedule in getting the "young boy" study rolling, thinking it would start this quarter - what happened? Same thing that has happened to the company time and time again - the FDA changed their minds on the trial design and data they want to see, so SRPT now has to work through all the nuances of generating valid MRI data as part of the trial protocol, before recruiting and treating patients. No big deal to the FDA, right - what's 6-9 more months to a kid that has DMD?
What a tool - a real "shocker" that you would post a mis-leading message. If by the "new ambulatory" trial, you meant to imply the confirmatory trial that is critical to the AA process, that trial (as I'm sure you know) has already started. The trial that has been delayed (again, due to the FDA changing their minds on what they wanted to see and deciding they want formal MRI data as part of the data set) is the trial in younger boys (i.e. less than 7 years of age). Besides that, he said they would start enrollment in q3 (not q4). Basically, all aspects of your message are erroneous and if starf wasn't around, you would be the biggest tool on this MB. Loser!
Practically, yes - if someone is holding a warrant that requires them to pay the company $10.86 per share, why would they exercise the warrant if the market price is less than that - if they wanted more shares, they would just buy them in the open market.
They don't need the cash - I'm guessing they are pushing some cheap shares to some "preferred" institutions and insiders. The warrant price speaks volumes - $10.86 - 3-times the offering price. When was the last time you saw a warrant price that high relative to the offering? I suppose if the Phase III trials get dragged out (they are waiting on a certain number of "events", so timing is uncertain), they may start to run low on cash, but they could have waited until the end of this year, when presumably they would have more mature data from the various Phase II trials - between that and the anticipation of the release of the Phase III results, the share price would surely have been higher toward the end of the year.
It will be interesting to see if the parents have the right to know the 4th biopsy results before SRPT may want to disclose them. On the one hand, it would be hard to put your kid through that procedure without having the right to see the results, but I'm guessing the company may have conditioned that with a non-disclosure agreement - i.e. you can see it, but not report/tweet/post/etc. to the outside world?
Huh - This has to be one of the quietest MB's out there - the only pumping I've seen recently on this board was for CRIS. That just tells me the day/momentum traders haven't gotten into the FOLD game, yet. That may change once they get some solid guidance from the FDA and hear back from the EU, then it should be a quick ride into double digits.
I don't love him - I just don't understand your incessant need to bash him with rants that are either false or make no sense. The fact that you can't understand the truth doesn't make the things he says wrong. The ONLY market that exists for an Ebola treatment is the US Govt (or some other western govt), but because you don't understand that concept, CG is wrong for stating it? What a tool!
What a dipstick - provide us one quote of CG "complaining" about the FDA. He has done nothing but share their communications and if anything has spoke about how responsive they have been. The parent groups are another issue entirely, but they have every right to gripe about how the FDA has handled the AA path for Etep. Once again you have completely missed the mark with your paranoid rants about CG. What a tool!
At some point the market will realize that all these RNAi companies using oglio delivery backbones are going to have a rough time trying to treat chronic illnesses. How will they be able to compete on a long-term basis, when their drugs cause liver problems, immune responses, etc., etc. ISIS is a $7B company with one approved drug that has a black box warning for liver issues. TKMR had its Ebola trial put on hold because of immune responses and we all know about RNA's list of toxicity issues with Prosensa. In the end, SRPT's morpholinos will have the ability to control the chronic/long-term indications, because it is the only delivery platform with a reasonable safety profile.
Trading at 25% of the price target - the market for small cap biotechs is broken.
nerd - Are you saying it will only be a month for the independent reading of the slides/data to be completed? I can't imagine the company will have "final" data reads on the 4th biopsies that quickly. I assume they will have to follow the same protocol of having 3 independent readings, like they are doing for the earlier biopsies?
No - the best news was just retweeted by Jenn - the Willis twins (the boys that became nonambulatory early in the trial) have agreed to 4th the biopsies and are scheduled for early Feb. The bashers point to these boys as evidence that the drug doesn't work, but the boys and their parents know that despite losing their legs (before Etep took effect), Etep is working to maintain their upper body and lung function. Why would they agree to do the biopsy if they didn't believe the drug was working for them?
What a tool - the reason I missed it is that they announced the collaboration back in 2013 and haven't said a word about it since. I was focused on the last couple of updates and presentations, which do not even mention it, which provides a pretty good idea on whether anything substantive is going to come out of this pre-clincial program in the near-term. IOW, you mentioning the Biogen collaboration as a near-term driver shows how clueless you are and the fact that you called me out for missing it shows you are worse than a smart@ss - you are a douchebag!