copp - after watching most of the AdCom, I am curious as to what the formal rules of "engagement" are for these panels. From what I could tell, the sponsor has no right to question or challenge any of the FDA's presentation (and vice versa) and when it came to the panel discussion and voting sessions, the sponsor was not able to join the discussion to clarify or correct any points unless someone on the panel asked them to. This doesn't lend itself to a very healthy analysis of key issues and the panel discussions reflected it - they seemed more bewildered than definitive in their conclusions and voting.
bionerd - the most disturbing thing to me was that all of the FDA's "evidence" against Etep's clinical efficacy was grounded in the comparison of the Etep boys to age-based natural history. I didn't notice it at the time the FDA's briefing docs came out, but they emphasized in the discussion of of the comparison to the CINRG loss of ambulation analysis that they believed the enrollment criteria for the Etep trial resulted in a trial population that was "enriched for patients with a better prognosis than the overall Exon-51 population" (see page 57). Nothing could be further from the truth and I can't believe SRPT didn't spend any time in their presentation focusing on how the FDA's age-based comparisons were not rational. At one point during the panel discussion, Kaye was desperately trying to state the point that an 11-year old with a 500-meter 6MWT ability is not the same as an 11-year old with a 200-meter 6MWT, but he was cut off and botched it. IMO, this should have been a key focus of their presentation.
Unfortunately, the AdCom did not have any real DMD experts that were able to bring this issue to light and hash it out, which would have gone a long way toward discrediting much of the FDA's analysis and presenting the data and experience of the Etep boys in the proper light - i.e. these boys were selected because they were on the verge of losing ambulation within a year or two and not outliers that would be expected to remain ambulant until for 4 years.
Just proves how stupid Cramer is if he thinks this opens the door for Drisa - the FDA would never approve that drug for safety reasons and given their history of failed efficacy results, it is very unlikely they would be able to design and execute a trial that would generate a hint of efficacy, let alone a statistically significant result. BMRN hasn't disclosed their strategy for Drisa since their rejection - IMO the odds are better they scrap the program, rather than continue to invest in a no-win situation.
Are you really that clueless - SRPT had no control over what parents decided to testify - every AdCom meeting is open to public testimony for a reason and it is not because the sponsor controls the process. If you watched the AdCom it was clear that SRPT had very little control over the proceedings - they were unable to directly address the distortions presented by the FDA.
Congrats - you secured the loser post of the day before the market even opened! The parents were fighting for their children's lives and the lives of all DMD boys - their stories are more relevant than all the distorted charts and graphs the FDA pedaled out.
thig - I don't have much faith in Woodcock - I suspect she was just playing good cop to the rest of the FDA's bad cop routine to appease the parents into believing it wasn't completely one-sided?
It was clear the panel was uncomfortable with the size of the trial and the historical comparison, so there was no hope of a full approval (Question 7). The question of whether AA was warranted based on the data wasn't specifically discussed or voted upon. The "science" did not support full approval and the "politics" of the adcom panel agenda did not allow the AA issue to be decided.
Was whether the "totality" of the data (including the parent/patient/doctor testimonies) was sufficient to warrant AA. Question 3 was whether the dystrophin results on their own were sufficient to predict a reasonable likelihood of clinical benefit and Question 7 was whether the data warranted full approval, which was never really a possibility. Not sure how the panel would have voted on that one - it was difficult to figure out if they simply didn't believe in the historical control comparison presented by SRPT (or the n was too small) or if they really bought into the distorted comparisons presented by Farkas? What is clear is that there are flaws/complications in both the 6MWT and dystrophin measurements that may not be resolved simply by increasing the N?
He dismissed Christine McSherry's "data" on falls before and after Etep as unscientific, but considers Farkas' quotes and data references from other studies/trials as more relevant? It is hard sometimes to figure out what AF's agenda is, but intelligence certainly isn't part of it.
But doesn't recognize the fact that any of those boys would likely have been excluded from the Etep trial for having a baseline walk level that was too high. He is totally clueless.
It is clear he has absolutely no direct knowledge of the disease and is simply cherry-picking studies and quotes that would lead to the questioning or variability of trial results - talk about comparing apples and oranges.
What's worse is his obsession with Beckers' patients and their dystrophin levels. There is probably less intense research and data available on Becker's, but he insists on using it as a comparison to dispute Etep's dystrophin measures.
It is clear from the briefing documents that the required basis for approval is The Perfect Trial - a placebo-controlled trial in which each boy is the exact same age, size and state of disease progression. Despite the fact that is impossible to achieve, that doesn't prevent the FDA from explaining away any signs of benefit in the data as a result of variability in the patient population or bias in how the data is analyzed. The 141M difference in average 6MWT (256 vs 114) at 36 months is explained by a theoretical potential bias in using historical control data. There is no assessment of how the control group was selected by SRPT or any specific biases identified between the two groups, just the fact that there is a theoretical potential bias is sufficient to dismiss the measured clinical impact of 3 years of treatment.
The FDA supposedly recognized the limitations and ethics involved in the trial design and and resulting clinical evidence in a rare disease when they approved the design of the confirmatory trial, but based on their criticism of their Phase II data, it is not clear whether the Phase III trial results will not be dismissed due to similar issues. There is no evidence that the position advocated by the USC letter - i.e. the best way to validate the clinical efficacy is to get as many kids on Etep as possible and assess them over the long-term - is being considered at all by the FDA. Unless a miracle drug comes along that actually does reverse the disease and get kids out of wheelchairs, these DMD boys are doomed, because no company is capable of designing and executing a trial that would eliminate all the theoretical biases and variability that could influence the data.
That is the problem with today's society - people have no shame. This guy raises issues with the data and trial that have already been resolved/explained, leaving him with this distaste for spending his "precious" tax dollars. If that is his concern, he should be writing letters about how the big pharma companies continue to screw the taxpayers by raising prices on blockbuster drugs, none of which are the only hope in treating a deadly children's disease. Embarrassment used to keep people from writing garbage like this - he is obviously a paid shill or has no family or friends to point out what a tool he is being.
As anxiety filled this AdCom will be for Exon 51 boys, it is even more so for boys with other Exons. If SRPT is denied AA for Exon 51, it is a 1-2 year setback for those boys, but that could translate into a 5+ delay for the other Exons. Without AA approval, SRPT will not have the resources to pursue the "lesser" Exons and it may not be economically feasible at all if the FDA does not allow some sort of "class approval" program to develop and instead forces larger Phase-III-type trials for all the different Exons.
thig - I hate to believe in that the FDA would act in such a vindictive or profiteering manner, but it is difficult to comprehend otherwise. How else do you explain an organization that claims to be working in a collaborative effort and then sabotages the company's NDA with false accusations.
xt - this post just proves how uninformed you are. Nobody disputes that steroids and PT will impact the progression of DMD, the "horse manure" is Farkas' blind speculation that the boys in the trial received higher levels of both - he had no evidence for that conjecture and the parents and doctors of the boys vehemently denied it.
That is the most disturbing aspect of the initial BDs - the FDA claims to have open communications with the company and parents in their efforts to bring a treatment to boys with DMD, but numerous points in the BD that were ultimately refuted could have been addressed with a simple phone call to the company. Instead, the FDA blindly made assertions about the boys and the tests that simply were false. If this didn't involve getting a treatment to dying boys, it would be another laughable case of govt bureaucracy gone amok.
berry - has he actually stated publicly that he believes very few new drugs work? That is an amazingly #$%$ statement from someone in the position to be a gate-keeper for live-saving drugs.
I agree with the fact that the new briefing docs will not be a "love fest" - has the FDA ever issued briefing docs that were overwhelmingly positive - if there were no issues to resolve, they would not even be having an AdCom. However, the idea that Farkas will "defend his position admirably" is equally ridiculous - many of his positions have been called out by the company, the parents and the doctors as being completely false or mis-guided - only a psychopath would try to dispute what experts have defined as reality. Practically, the new BD are likely to raise questions or express concern over the validity of certain test results, instead of an in-the-face attack that the results are meaningless, as the first BD's did. Anybody that believes that the FDA is going to express any positive views in the BDs (other than safety, which I'm sure they will still find an avenue to question the long-term safety risks) is kidding themselves.
I thought you were talking about partnerships for some of their new GPCR or early pipeline drugs - he was talking about marketing deals for Omidria. I'd like to think that they can generate significant sales for Omidria outside the US, but remember that it has been approved in Europe since August of last year - Omidria should not be a difficult drug to market and distribute, so the fact that it is taking the better part of a year to get any kind of agreement in place would indicate that the opportunity must not be that significant?
I have been listening to Dr. D talk up the GPCR platform for the past 4 years - he presents it as if they have the rights to whole classes of new drugs that could eclipse all the currently existing drugs and yet they have not licensed a single molecule or patent position in their entire portfolio. He needs to either prove there is value in all this GPCR work or stop talking about it, let alone wasting company resources on the research.