for large, complex Phase I-IV trials. Phase IV clinical trials are post FDA approval, ie confirmatory after Accelerated Approval
It is entirely possible that "submission" is a multi-step process involving, among other things, a summary of the data in text form, a write up of procedures used (remember, there was a detailed discussion at the Mar 15 2015 workshop, an a review/audit/questions on the data and procedures. So when do you disclose-the initial sendin of data, the steps along the way, ??? There are good reasons for not disclosing anything if the process is more than one step, until the final approval and results are released.
read about the Myozyme 2008 AdCom where just before the meeting FDA proposed a sensitivity analysis of 6 mwt which Genzyme said was not appropriate. On primary 6 mwt they had 28m benefit v placebo. Eteplirsen has a 120-140 m benefit and pulmonary benefit
(one good question asked at Sarepta adcom was do you (FDA) have a mathematical analysis rather than just your overlapping line drawings to support claim Eteplirsen treated boys having same disease course as DMD natural history)-which FDA staff did not have, because Eteplirsen recipients dominated. overall, the results of untreated patients. Dominated in a game theory sense, ie if you had to choose a strategy, which would you choose go on untreated, or have Eteplirsen and get likely beneft- aboutvwhat Wagner, Connolly and Bryne testified to at AdCom
FDA Advisory Panel to Discuss Genzyme's Myozyme BLA on Tuesday
but it got approved after delays, including in one case a 90 day PDUFA extension.
Although they haven't announced it as 90 days, 3 months past prior PDUFA date would put it
around Aug 24, but who knows if a different procedural path (this claimed DPO BS) would alter
the 90 day timeline. But they have to know 100+ members of Congress and Senate are
watching and waiting for an explanation of any result, plus several thousand DMD patients
and their families.
FDA processes will finish, including post marketing commitments negotiations (because they know they're giving Sarepta a $300 million pediatric priority review voucher, so they can hold the company up for as much
more detailed studies as they want), the Accelerated Approval labeling (describing the indications and uncertainty) the risk benefit table required by FDA's PDUFA V commitments for use in 2016, and all the other details, and FDA will announce with great fanfare that they have approved the first treatment for DMD.
6mwt + de novo dystrophin + no threshold + animal model evidence od low level dystrophin benefits + 1 trial and confirmatory evidence + 51 4 years and 45 and 53 underway + PROS FROM JETT = A multiplicity of evidence = substantial evidence permitting approval that drug likely will have intended effect
Sep 19 #MakeDuchenneHistory #RaceToYes #ToTheEdgeoftheSky made history - just first step for PMO antisense biotechnology, one great step (actually +160m) for DMD
Yes, as suggested for driasapersen, showing exon skipping for other exons, 45, 53, by this second generation PMO can validate the first exon 51 - this is how precision medicine needs to adapt to providing tailored drugs on a class basis to specific mutations which need corrective therapy, rather than one drug at a time. the conditions for the confirmatory trials appear to provide that positive results on one of the trials can result in termination of other required trials.
At least you didn't have to sell 24,000 shares under 30 as part of a pre-planned executive disposal in order to avoid giving any indication of impending approval. But thanks for all you did to get to this point, ChrisG
1. The approval is conditioned on extensive post marketing commitments
2. The disease, and MOA of eteplirsen, producing dystrophin, is well understood, a good biomarker
3 The DMD community rep at AdCom said she will support withdrawing approval if confirmatory trials fail.
4. The Review Team presentation was really hokey as Woodcock said (hokey is a euphemism)
5. Unger dispute memo and the review discussion ignore the multiple experts in favor of eteplirsen at the AdCom ie, where is the discussion of the 36 signee letter-not in mind of Review Team, but Woocock knows
who Kunkel, Connolly, Wagner are who said patients were benefitting
6. Claiming to be familiar with the literature does not mean certainty about the dystrophin level necessary to slow progression to an extent less than Beckers
7. There was, and continues to be, Real World Evidence from the confirmatory and safety trials (like the Jett presentation about less falls in a careful PRO/CRO record of benefit from a more recent eteplirsen beneficiary) Multiple new trial boys testified.
8. The Review Team discounted eteplirsen boys not having reached median Loss of Ambulation despite differences in CINRG defn, ie full time wheelchair use
9, FDA at a recent PDUFA reauth mtg said they had few (5) statistical experts on patient report use, maybe this will stimulate more (same with biomarkers)
10. Woodcock correctly looked at totality of evidence to see if it was substantial - clearly eteplirsen induces dystrophin, the MOA, some boys 5/12, 8/12, 10/12 were benefitting, as were newly treated patients; as one advocate put it, some dystrophin is better than no dystrophin, and Kunkel said he didn't see level produced by eteplirsen in DMD untreated boys.
not all you need to know-want to see structured risk benefit table which is a PDUFA commitment for approved new drugs in 2016. Where is the benefit risk disease evidence conclusions table
Twitter people say CIGNA broad coverage in view of indication, safety
Actually, an insurance company can be sued for 1) breach of contract 2) bad faith denial of coverage; 3) punitive damages, which in the case of a DMD patient could be humongous. California has detailed fair claims settlement practices that must be followed in Title 10, Chapter 5, Sec 7.5 regarding Fair Settlement practices, and other states have their own insurance regulations. There are a million lawyers who would like a bad faith refusal to cover case against Anthem, and the discovery would go to their decision making, motive (including profit motivation), physical harm suffered by patients, emotional distress, and family burden. Just one denial could cost them millions. Makes the Health Net class action settlement look tiny, compared to Anthem;s exposure for denial of a drug which could slow a progressive disease, leading to irreversible harms. Just search bad faith insurance to get a list of firms which would have background on this contract and tort litigation.