"A confirmatory trial and acceptance of an NDA and subsequent AA are going to happen and soon. That’s the only option FDA has given the heat.'
That seems to be the corner they're in. It seems inevitable as the outcome. ... dot dot dot ...
You forgot this reason for not partnering DMD - Chris was rightly worried they could pull the plug on it at any time. Since some suspect Big Pharma is nervous about the potential of RNA therapeutics generally, wouldn't that have been something our partner may well have done - if only to stick a knife into the RNA field? Crazy? From what I've seen lately, not at all. Chris deserves a medal if he pulls this off. Two medals. The second for not doing any corrupt under the table "goodwill" payoffs that Starfe is faulting him for not doing.
That's not implied and I wouldn't expect it. I would expect at best a definitive trial design agreement with the FDA saying "Also, Sarepta has addressed our Nov.12 concers about an AA application and they may go ahead and apply." something like that. I'm sure they'll want to see 3 months of safety data from the phase 3 before the climactic moment.
Other than the dosing date, Chemdeps, I completely agree with your expectation: after 3 months of dosing they check the safety profile, they look at how the original 12 kids are doing and they approve Sarepta's AA application (or NDA or whatever) and approve it at the exact moment there will be enough drug available to start selling it. Been saying this for over a year now and .... and .... and .....maybe ....maybe ..... maybe.....
From Hong's paper: "...To search for more effective muscle-homing peptides, we carried out in vitro biopanning in myoblasts and identified a novel 12-mer peptide (M12) showing preferential binding to skeletal muscle compared to the liver. When conjugated to morpholino oligomers (PMOs), approximately 25% of normal level of dystrophin expression was achieved in body-wide skeletal muscles in mdx mice with significant recovery in grip strength, whereas less than 2% in corresponding tissues treated with either MSP-PMO or unmodified PMO under identical conditions. Our data provide evidences for the first time that a muscle-homing peptide alone can enhance AO delivery to muscle without appreciable toxicity at 75 mg/kg..."
This is a PPMO not a PMO-X. Sarepta's keeping the PMO-X secret so I doubt there any new data out today on it.
Photomorpholinos.....That's a new one. Certainly SOUNDS good!
"....Core–shell fluorescent upconversion nanoparticles excited by highly penetrating near-infrared radiation and emitting simultaneously in the ultraviolet and visible ranges were synthesized and used as remote nanotransducers to simultaneously activate endosomal escape and gene knockdown. Gene knockdown using photomorpholinos was enhanced as much as 30% in vitro compared to the control without endosomal escape facilitation. A similar trend was seen in vivo in a murine melanoma model, demonstrating the enormous clinical potential of this system."
Couldn't get the Hong article via Google, though.
Article title: "The FDA Returns to Its Dark Ages"............Astrue makes a strong case that the FDA constantly has reverted to refusing accelerated approvals ever since 1993 when the president and congress brought the AA concept into existence. According to the author, there was a 5 year moment under an FDA head who repeatedly had to override his underling's AA rejections . He died in 1999 and it's reverted back since- except with respect to rare cancers apparently, probably for pr reasons.
This author obviously was there, has the credibility, and knows of what he speaks, and I was sad to hear about what he said is still going on over there. I really had bought the hype and believed they had changed. That seems to have been a pipe dream - for the last 21 years, I guess. It's a sad state of affairs where it still seems to take a Hamberg or a President to run roughshod over those working below them to get the kind of actions President's and congresses have been demanding of the FDA since 1993. This DMD case hopefully will begin a process of reform that finally lasts over there. It probably will take people with real backbone and sticktoitivness to make it last, but they may be found some day soon.
It's normal. When something meaningful happens, we'll hear about it. By law.
Of course you are doing exactly what the Big Boys want you to do. But we all know where you're coming from, believe me.