I'm rarely wrong. Not only do I know the efficacy standard for Accelerated approval per FDA 2012 statute, the AA standard appears in all the recent FDA "Guidance to the Drug Industry" on standard for efficacy. Janet Woodcock, Director of Drug development for the FDA agrees with me. Here quotes during the Adcom are well documented. Ed Kaye and sarepta overall have used this standard to file for AA. The Biomarin CEO referenced this AA standard after Drisa was rejected. The "substantial evidence" standard originates in the 1962 statute when the FDA transitioned from a safety only regulatory body to one that regulated efficacy and safety. The standard for ALL drugs Except AA for serious and deadly disease states is "reasonable likely to confer a clinical benefit". You are the one that is wrong.
Ed Nash covered AVII in the early days and he was a victim of Denis Burger's misrepresentations. He still holds a grudge. He knows better.
OPPY analyst Marai reports that her research has revealed that many negative votes have been uncovered which resulted in the FDA throwing out the adcom negative votes and approving based on "unmet need". That's all I have right now but when I receive the report I'll post it.
I didn't read the article but it makes perfect sense. Glucose cellular uptake is passive and active [ATP]. Increased presence of glucose intracellularly increases metabolic processes which will increase membrane transport dynamics. Many studies have been conducted on glucose uptake and exercise. It's about time someone conducted one on glucose uptake in skeletal muscle. I look forward to reading study.
Ru, I fully expected you to agree with Farkas's pseudo-scientific analytical conclusions on dystrophin quantification. Immunohistochemistry IS a more sensitive method for quantifying dystrophin. Don't believe me, then read the latest comparative analysis of quantifying dystrophin by both Western Blot and IHC in the Journal Neurology , Nov. 2014. They conclude that IHC is MORE sensitive then WB. Yahoo won't let me post link.
Michael, Sarepta did not mislead Dunn/Farkas. Their contention is based on SRPT reporting %+ fibers vs. baseline dystrophin. Farkas's issue with IMF is that he doesn't believe IMF should be used for dystrophin quantification while SRPT and DMD researchers like Chamberlain and Kunkel believe it is the only way to quantify and localize functional dystrophin. Farkas believes that only Western Blot should be used for quantification. Both techniques of quantification have their shortcomings but the latest research by DMD scientists is that WB cannot accurately quantify small amounts of dystrophin [lower limit]. There are other problems like fragments, degradation, variability introduced by a very complex preparatory process. The latest advancements in IMF use very specific and accurate software to count dystrophin. In the briefing docs Farkas makes that accusation that SRPT "enhanced" the slide images to make it look like dystrophin was present when it wasn't. Here Farkas was caught in a lie. Sarepta clearly only enhanced the images to illustrate, for image presentation, dystrophin localization. The actually counting of dystrophin utilized the original slide images. From my perspective the only dishonest actor in this process has been Dunn and Farkas.
Ru, Last time. Farkas and Dunn are citing the 1962 law while ignoring the 2012 FDASIA/AA superseding law. 1962 law transformed the FDA from only a safety evaluator to a safety and efficacy evaluator. This is a generalized law that delineates guidelines, protocols and standards for all drugs at that time, 1962. In 2008 and 2012 Congress modified the 1962 law by creating the FDASIA and AA laws. These laws replace the "substantial evidence" standard for Rare and Deadly diseases and changes it to "reasonable likely to provide a clinical benefit" This is a fact and cannot be changed by someone who refuses to deal with reality. Director of Drug Research Agrees that the AA standard should apply to eteplirsen
Farkas's following statement receives my vote as the worst by an FDA official in history..."The boys could walk if they would only put their minds to it". This guy is the team leader of the Peripheral Committee.
Adam F. didn't suggest it. He reported quotes from Woodcock own words. It was easier for me to quote Adam's article then it was for me to access transcript. Be intellectually honest for once.
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.
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
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
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.
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
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.