thigrls, I am always amazed how people forget what you posted. CG may not be the super best CEO we could have but as grey and you and others state--he is the best SRPT/AVI has ever had. I agree that without him we might have been delisted by now or bought out by GSK for pennies on the dollar.
"From where I sit, the FDA has wasted plenty of SRPT's time and money by suggesting an NDA was a viable option, when in fact, it was only an option when they thought their favorite - GSK - would make it to market first. Once GSK exploded, the FDA decided to change the rules of the game by conveniently misinterpreting "new" data. Freaking travesty."
Spot on Grey. The minute GSK was out---the FDA was like SRPT who??? Travesty indeed!
Tred, spot on. However, I am afraid this goes much deeper. The FDA is being circular because deep down they are clueless about how to deal with this given their fear of drisa failing phase 3 somehow being repeated. They initially agree to trial guidelines and design and then reverse themselves. CG has always said he had close dialog with them and felt they were very communicative, etc. To my thinking, the FDA now is saying we don't know what is the right way to design the trial, what we told you and agreed to initially has turned out to be wrong due to drisa failure (I am not saying this is rational on the FDA part), ..... so why don't you innovate a new phase 3 trial design -- but again we have shown we, the FDA, don't know exactly how to understand all of the issues of the trial and dont' know if what you come up with will be ok in the future....so better yet, why don't you let GSK design the trial or partner with GSK to design the trial since they know more than us and will spend lots of money in many ways and besides we trust their clinical design capability more than SRPT....and ultimately that will make us, FDA, feel much more comfortable. And therefore more likely to approve etep in the future.
In other words, we, FDA, aren't going to admit we wasted srpt time and money and kids lives by approving their initial trial design...no, instead, we will do a 180, and say start from square one again ...or imply without saying directly that since we were all on board with GSK's trial design with breakthrough designation that maybe you and GSK should partner to help get etep approved. With srpt's better drug and GSK bigger $$ and clinical experience this still seems like a forced shotgun marriage to me--even though such has never been explicitly stated by the FDA. The FDA is using circular logic to force srpt into a corner IMO.
neo, sure I lost a lot of money and that sucks. But this goes waaaay deeper than that. If the FDA thought this way about the study size needing to be larger now, then why did Temple say it wasn't an issue months ago? If the FDA allowed GSK (as many have already pointed out many times recently) to claim 6MWT was a valid endpoint, then why call it into question now despite it being the gold standard for DMD clinical measurements for so many years? Why bring up other possible endpoints that have not been validated at all and thus could cause a further delay if the FDA decides willy nilly that after SRPT uses these new endpoints (that, of course, the fda originally suggested) that the FDA doesn't like that data and SRPT has to redo the phase 3 trial yet again?
Come on man, this is much more than money loss -- this is a breakdown in confidence and trust in the system. The regulator helping the big pharmas who politically/financially grease its palms. How does a little biopharma that chooses to go it alone stand a chance in hell of succeeding when, even if they come up with an amazing drug, the regulator decides to invalidate everything they initially said was ok. You can't be serious that you think this is only about a money loss.
This FDA nastiness smacks of either laziness, incompetence, corruption or a combination of all three. Who is going to regulate the regulator when you can't trust them?
Etep works -- IMO the data are conclusive. Mcdonald even stated that. What has shell shocked the parents/boys, SRPT, investors, CG etc is that the confidence and trust in the clinical process/approval with the FDA has been shaken to the core. This reversal by the FDA toward the phase 2 data along with no clearly defined phase 3 trial endpoints has left everyone shell shocked, bewildered and confused. How in the hell do you trust the FDA behavior going forward when they pull #$%$ like this???
"FDA literally destroyed the company"--a bit exaggerated but it does feel that way. The FDA seems to have invalidated waaaay too much of etep progress in one very harsh message. They called into question methods, data, analysis with whatever ammunition they could find--even if a lot of that ammo was nonsense. Maybe you are right--maybe something really bad happened between CG and FDA that we still don't know about.
Yep, IMO FDA forced a shotgun marriage between SRPT and GSK. Even if they don't exactly say it, when you think it through as you, I and others are doing---it sure seems clear.
Regurgitory excrement you are one of the lowest pieces of vile trash I have ever witnessed in any communication forum. You better pray you don't meet up one day with me or some DMD parents in person. Think about it you #$%$ up SFB.
I am not trying to waste board space. What I am getting at, is that perhaps contrary to my recollection of the event and possibly others--the pure FDA statements are not nearly as bullish as CG's interpretation of their statements. The FDA was cagey back then too. The FDA did not literally say the data is significant, meaningful and shows great promise (especially "shows great promise"). Not even close. I agree I, and most of us including CG, felt we could reasonably interpret that the spirit of what the FDA said was more bullish. But after this apparent 180 reversal by the FDA it seems they were giving themselves a cagey way out if they needed it-- regardless of the spirit of what they wrote. I agree and agreed back then with your take and CG's take that an early NDA might receive a positive response. I think now, in light of what just happened, its clear the FDA were trying to give the parents hope and get some of the advocate and political pressure off of their backs by appearing to be open and flexible. They may have been cautiously optimistic but as soon as the GSK trial failed they bailed and became ultra conservative. Did the FDA give the parents false hope, especially with their parent meetings? You bet but they argue they are "protecting them", etc.. Did they mislead CG and investors--probably but they couldn't care less about that --even if it means delaying the drug more years--even if it hurts more boys--because they are "protecting them".
In other words, you can't trust a #$%$ thing the FDA says in their bureaucratic politico speaking voice and can only go by their actions. But they are masters of that fake speaking voice and can cause incredible harm to many -- just like politicians do all the #$%$ time!
I went back and looked at some of the key conference call discussion from July 23 which was the regulatory update. Here are the key phrases:
The FDA stated in pre-meeting comments that the Agency is "open to considering an NDA based on these data for filing." The Agency, however, requested additional information related to the methodology and verification of dystrophin quantification. Sarepta believes the requests from the Agency can be addressed and incorporated into an NDA submission in the first half of 2014.
"We are encouraged by the feedback from the FDA and believe that data from our ongoing clinical study merits review by the Agency and will be sufficient for an NDA filing," said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics. "We plan to work closely with the FDA to prepare an NDA submission in the first half of 2014 as we continue to prepare for our confirmatory study and our manufacturing scale up."
The Agency would not commit to declaring dystrophin an acceptable surrogate endpoint under the CFR 314 Subpart H Accelerated Approval pathway prior to an NDA filing and commented that a decision by the Agency to file "the NDA would not indicate that we have accepted dystrophin expression as a biomarker reasonably likely to predict clinical benefit. A filing would only indicate that the question merits review, and that we deem the data to be reviewable."
simp, that is an interesting take and sort of has been in the back of my crazy mind. I wonder if the FDA didn't like the way CG was reporting the events of their meetings or getting patient and investor hopes too high and so made sure they had him release the very strong, perhaps harsh, negative statements about how the FDA views SRPT trial design, methods, etc. Sort of like "we(the fda) don't want you to spin this anymore--just make sure that you release these exact words to the patients and investors. While we can't actually stop you from adding your spin we can make sure you release the statement we tell you to release and we will write it to be quite clear on how we see things as opposed to any spin you might put on it later, etc. We are irritated that you have stoked hopes in the patient community to be higher than we thought we had communicated to you in earlier meetings and as a result of how you spun it we were (and didn't like ) being backed into a corner with all of the advocate and congress pressure on us, etc."
Or I could be totally FOS with this thinking. But I do agree, the FDA statement came off harsh and invalidating --- waaaay more than we might have expected from our knowledge about their previous communications to srpt.
aaaaa, YMB strikes again. cont'd GSK could offer $25/sh and might just get away with it. Sucks big time. But the silver lining might be that the boys get their drug earlier
grey, that is why, and I suspect you agree, as I said earlier, the fda wants a big pharma to manage this and so is siding with GSK's data "interpretation" continually. Instead of realizing that GSK messed up their trial design, etc.---- no...its more like fda thinks srpt now doesn't have a large enough N (even though they told us N wasn't an issue earlier), and their data analysis is wrong, and dystrophin isn't a valid marker, and,and, and....
Now add in what other posters have said about the europeans being ok with dystrophin and we know GSK has exclusivity for exon 51 there..... Yep, the propeller on my tinfoil hat is moving at warp speed. I smell a GSK buyout offer for a poor price all complements of the FDA. At this point I would bet GSK could offer
enigmatic, these are new endpoints and have to be proven with additional testing which means more time before you can finalize the next phase 3 design. The fda is giving suggestions to endpoints--but that still means the sponsor (srpt) has to validate those endpoints and choose them properly otherwise poor trial results may occur which will occur further delays.
If time were not critical here, then, sure get more data and more endpoints. But it is critical here. Very critical. FDA is adding more complexity and time to a therapy that the dmd patients have been waiting for their whole lives. If it was feasible to enroll the much larger patient numbers now needed for the full phase 3 trial just by using 6MWT then that might be ok. Although, I still believe they have to decide what those additional endpoints are show them to be robust statistically which still takes more time. But the FDA knows srpt will have a hard time finding 120 boys for the phase 3 that will be valid for 6MWT which is again more time. It comes down to a lot more time for boys who don't have any. Get it now?
enigmatic, they suggested ways to measure progress but none of those ways have even been validated by the scientific community. I can suggest they measure biceps strength but who cares what I suggest? Whatever additional method is used needs to be peered reviewed/blessed to have credibility. That is why some analysts on the conference call asked if it would be a good idea to do additional phase 2 trials to validate these other endpoints. Sure check everything a million times and masturbate on every #$%$ detail and then the FDA will have covered its #$%$ more completely or, worse, forced a sell of srpt to GSK. This all takes additional time and meanwhile, dmd boys wait and get sicker.
Yes, and according to CG all of the big FDA honchos including Woodcock were there at that meeting last friday. I gather they meant to show a sign of solidarity behind their belligerent decision. Sort of like telling the parents we have made this decision and we are ALL behind it--you can complain but we are all on board -- so good luck. In a way the FDA is being as inflexible as they claimed they were going to be flexible about this trial. Truly phony, vile, #$%$ behavior.
None of us longs get it. This 180 reversal came out of nowhere and the FDA statement was nasty and invalidating to all of the phase 2b trial on many levels. Calling the FDA stupid is being too nice--more like corrupt and lazy and disgusting.