neuro, don't expect an intelligent reply. Biochemistry is not one of his strong points. He's a great lab tech and pontificator of FDA history. Unfortunately he hasn't read any of the FDA's updates since the 1962 law empowering the FDA to judge efficacy of drugs. This is where "substantial evidence" appears as the efficacy standard.
506 C of Accelerated approval Law...VII. ACCELERATED APPROVAL
The accelerated approval provisions of FDASIA in section 506(c) of the FD&C Act provide that FDA may grant accelerated approval to:
. . . a product for a serious or life-threatening disease or condition . . . upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
For drugs granted accelerated approval, postmarketing confirmatory trials have been required to verify and describe the anticipated effect on IMM or other clinical benefit
Cytokinetics is one of the biotech companies that is being considered as a takeover target of sarepta's once eteplirsen is granted AA. They have a complimentary pipeline of drugs that could be used to supplement SRPT's DMD pipeline. Ed Kaye is now on their Board of Directors is an advancement of that goal.
Agreed. MDA has 25% admin. costs which is way too much to spend for a charitable organization. No one should invest in any charity that spends 10% on admin. costs.
What is being lost in the interpretation of the accelerated Approval statutes and FDA's guidance on said statutes is that a biomarker alone could be the sole basis for AA approval. I could make the argument that decreasing creatine kinase levels could be reason enough to approve eteplirsen.
johnny, It has been a long time. I remember when AVII went public in 1997 and Jim Summerton was posting on the Yahoo message board explaining why he was no longer part of Antivirals/AVII. What a ride.
Ru, I have posted the 2008 and 2012 PDASIA Accelerated Approval law passed by Congress and signed by the President. I've posted the FDA's Drug Industry Guidance for AA. I've posted Janet Woodcock's own words at the recent Adcom. Other FDA committee's have followed the new AA standard and granted approval under FDASIA. Sarepta's CEO and Biomarin's CEO all filed for AA under guidance by the FDA with the understanding that the standard is "reasonably likely to confer a clinical benefit". The Biomarin CEO stated immediately after Drisapersen was rejected by stating that he hopes the FDA uses the same substantial evidence standard towards eteplirsen as the FDA used for Drisapersen. I can't explain why the FDA left up an old web page citing the "substantial evidence" standard for AA but if we apply Occam's razor's simplest explanation principle, a gov't bureaucrat failed to remove page. Is that the conspiracy theory you are advancing??
stockpick, I am also a cynic but this call is not based on cynicism but a rational analytical view of ALL the variables and an avid watcher all things FDA and bureaucratic political behavior
I have to admit that the eteplirsen upcoming AA approval is one of the easiest approval calls I have seen in a long while. The Zohydro approval was much more difficult then this one. 6-7 against approval @ Adcom based on negatively convoluted queries, based on 2 "NO" votes who post adcom vote stated that the drug works, based on Janet Woodcock correcting the adcom's AA approval standards of "substantial evidence" to "reasonable likely to confer a clinical benefit" [Sorry RU], based on an unrivaled public relations campaign, based on Orphan disease with no effective treatments and 6MWT advantage of 161 meters over matched controls, based on the superiority of the Sarepta/FDA supported matched historical control vs. Farkas's "MIXED" historical control of Becker's, exon 45/53 and inconsistent steroid therapy and finally based on U.S law via the 2008 and 2012 FDASIA on AA and the upcoming Congressional inquiry into the practices of Drug approvals that are not only fair and unequal but contrary to the law and FDA's own guidance to the drug industry on AA approval. Janet Woodcock is not stupid.
PPMO is completely different from the PMO+ chemistry. The PPMO used in the restenosis Cook trial was rushed without due scientific diligence. The peptide they used was arginine-rich and coating on a stent or spraying via a catheter delivery method results in high levels of arginine in the arterial endothelium. Research has demonstrated that arginine triggers cellular proliferation, just like atherosclerosis, in arterial walls. In rushing this to the clinic someone forgot to review the research. Cook had complete control over the PMO/PPMO trials so the blame is theirs. There are several PPMO's that SRPT has developed with Hong Moulton as lead biochemist on the project that are very safe at therapeutic levels.
stockpick, I didn't report that the FDA was inspecting the Sarepta manufacturing facility. I posited a possible explanation to increased calls action. That's all. The FDA would have to reinspect before approval.
When the FDA is about to approve a drug they have to conduct another inspection of the manufacturing facility. If the FDA is doing that inspection that would mean they are ready to grant AA. That scenario would leak out.
"Substantial evidence" comes from the 1962 statute. There was no Accelerated approval pathway back then. Congress, acknowledging a need to address small population diseases with high mortality rates passed new laws changing the efficacy bar for AA to reasonable likely to confer a clinical benefit. A confirmatory trial is required and then substantial evidence bar should be applied. Read the 2008 and 2012 statutes. The real question is why the Farkas adcom committee is not applying the AA statute efficacy bar. Janet Woodcock repeatedly stressed during the adcom that the reasonable likely standard is the proper to standard to use for AA. John, are you ignorant of the AA statutes or are you just a "short" stooge? Either one works for me.
redlaw, The adcom vote on zohydro was after the phase III trial dataset. Straight approval. Hamburg was the Director at the time for the FDA and she influenced the total vote to approve disregarding the adcom recommendation
Due to the great public interest involving the FDA's upcoming AA decision the FDA will issue a Press Release like they did the the Keytruda AA approval. Janet woodcock will want to counteract all the bad press the FDA has received after the Adcom debacle by issuing PR. For those who believe that the FDA will issue a CRL, the Ron Farkas inspired adcom circus the final dystrophin vote was 6 for approval and 7 against. factor in a couple of the panel members comments post-Adcom and I guarantee eteplirsen is granted AA approval. Woodcock is no fool.