What happens if the FDA Adcom votes down the efficacy questions and issues a CRL but then PhaseIII data proves eteplirsen effective with no risk? The FDA will be responsible for hundreds of exon 51 boys progressing 2 more years without treatment. Disgrace.
Historical controls are more representative then placebo controls based on a clinical trial historical analysis. Ouch! Farkas is looking really out of his league. FDA brass is throwing him overboard.
Dunn and Farkas are adamantly against the implementation of PDASIA and Accelerated Approval statutes in their committee. This was obvious by both briefing docs and Farkas's rambling presentation. He came across not as an impassioned, objective regulator but as a partisan, subjective hack. Over the last couple of years the FDA has conformed the different FDA committees to allow patient advocates to vote on these committees. I believe this was to much for Farkas to bear because it dilutes 2 of the other committee voters. I believe Farkas inappropriately lobbied committee members to vote according to his analysis of the data package. I make this charge not because I have some inside source, I don't, but I base it on the question regarding the 6 MWT. In the question it states... was the design free of bias and was it well designed [paraphrase]. I still do not understand the rationale for that specific vote. In the Drisapersen data their 6MWT scores on a post-hoc subgroup was 20 Meters. Farkas stated in his diatribe that Biomarin's data package was more robust. SRPT's participants score 161 meters. He completely change well established endpoints on its head. The FDA has a real problem with this committee leader. I still believe there will be a push by FDA officials to influence the overall vote late May by pushing for AA. Question #2 re: dystrophin was a 6-7 vote and I can understand members voting against this biomarker based on levels because it is an unknown but not because these members do not understand the quantitative value of IHC. In medical school they are taught that Western Blot is the gold standard for protein quantification. In the 1990's and prior it was but research has progressed and Farkas and company have not.
Here's a blurb and quote from a "behavioral science" guy. He concludes in his post vote comments as stating dystrophin levels to low to predict clinical benefit. If there was one overwhelming fact on display from researchers who commented at Adcom is that the exact amount of additional dystrophin needed for clinical effect is unknown and is probably very low. This guy bought Farkas's Beckers BS. Chiadi Onyike, MD, associate professor of psychiatry and behavioral sciences at John Hopkins University School of Medicine, voted against approval in either an accelerated or conventional approach.
While eteplirsen may have caused the production of some dystrophin, "it's very small ... too small to go from dystrophin production to clinical effect,"
Don't know if this was posted yet but this from the NY times...The following comments support my previous comments on Farkas and Dunn...Dr. Bruce I. Ovbiagele, chairman of neurology at the Medical University of South Carolina, voted against approval but said, “Based on all I heard, the drug definitely works, but the question was framed differently.”
Agreed. The rhetoric surrounding the Improvi trial design is without merit.The 6MWT and Dystrophin are bedrock endpoints for DMD. Just because Farkas castes doubts on trial design and endpoints doesn't make it true. There is no way Farkas is involved in the Phase III confirmatory adcom. He's about to get spanked.
After panel vote and top FDA officials attended including Woodcock and Temple. People who attended said that Woodcock and Temple were very engaged with DMD advocates at dinner. Attendees have all concluded that this isn't over. This was the reason for yesterday's big recovery after a negative panel vote.
arien, Zohydro is a very good comparison. It's the story behind the approval that is really interesting and it accurately applies to eteplirsen's upcoming approval. Zogenix's [zohydro] in their Adcom data package reached all of their confirmatory trial endpoints but the panel members voted "No" because of the addiction epidemic in this country. Zogenix CEO was shocked at the vote. Do you know why they were shocked? because the FDA advocated a weaker version of oxycontin [oxycodone ER] [and competition to oxycontin] and helped Zogenix get to the finish line. Once this happened I recommended everyone start buying up shares of ZGNX for .50 cents a share because the FDA HAD to approve because of their commitment to Zogenix. I also told others that after the initial approval runup they should sell because a "blackbox" warning would come too thereafter. It did. This is exactly what has happened so far with re: to SRPT. This will be approved come late May and all these ignorant financial journalist who say that "Science wins out over emotion" in adcom rejection will all have to eat major crow May 26th.
Tred, Agreed. I also was told that Steve Wilton was there to rebut Farkas's western Blot and IF conclusions and work into his comments changes at the cellular level of eteplirsen treated patients. Did not happen. I liked Christine McSherry's presentation in the am session immediately after Ed Kaye but SRPT should have used that time to focus on question #2 dystrophin endpoint. This is where Wilton could have made a better case.
Yahoo won't let me post link but it is a video link of his dystrophin research on % + fibers and their effect on adjacent fibers and his 30 year research demonstrated that even if there is small amounts produced provides significant clinical benefits in animal models. One can find link on twitter or Google
I am not a big fan of his but today's article is a must read. He objectively reports on the panels questions to janet Woodcock and bob Temple. When queried about the "standard" they both repeatedly state' " reasonably likely to confer a clinical benefit"..... Posters who don't believe that Woodcock has a big problem on her hands are kidding themselves. She is keenly aware that the committees use of "substantial evidence" is contrary to the PDASIA / AA 2012 law.
Agree with all the negative comments about his adcom/blogging commentary but on rare occasions he can be an objective reporter and today's article is just that. This is the reason the stock is doing so well in early trading. This was't subjective commentary
So do still believe the efficacy standard for AA is still "substantial evidence"? This is Janet Woodcock, Director of Drug Development and Research at FDA, addressing the panel before the vote as reported in a summary by Adam F. "Woodcock invoked the "reasonably likely" accelerated approval standard four times in that single statement. "Reasonably likely" offers a lot of leeway and flexibility to say yes. She reminds the panel members that there's no established dystrophin production threshold for DMD". Bionerd=10...Ru=0
Red, Just read your post and you know for sure that the panel members were told only to consider the Adcom Briefing docs? This is reversible error.