I'm not sure there is going to be much to celebrate from the MRI data. The impression from what limited discussion there has been from management is that the 11 Etep boys may have had one or two MRI's performed, but there is probably not much more than a baseline measurement showing how much deterioration had already taken place in their leg muscles. This may help validate there intended enrollment status as boys on the verge of losing ambulation, but not much more?
If it both the pancreatic and STS pivotal trials are successful, $14 will be conservative. If some other Phase II trials (glio, lung, MM, etc.) show benefit and the market starts to believe in the breadth of indications for TH-302, then $30+ is feasible in a couple of years.
I think the "market" is still skeptical on the value of Omidria and may want to see how the launch goes. There are several analysts with targets well above $30 - it will be interesting to see if any of those analysts push their price targets due to the CMS pricing? It would also help if they got the PDE10 trial resuming enrollment - that will be a big part of pushing this stock over $30 late next year, if they can show preliminary efficacy with the PDE10 drug.
I don't think the analysts' models were counting on it and I believe the pricing of $400-$500 is above the $200-$300 they were assuming. Omidria could end up being a billion $ drug.
Obviously, this was the most damaging phrase in the FDA minutes and the damage was maximized by the fact that they provided no examples or details on what the supposed "disparities" were, leaving analysts and investors to speculate on the worst possible scenarios. We obviously know two things - the hospital that did the work is one of the leading hospitals in the country for DMD research and treatment and that the measurement of dystrophin-positive fibers is a subjective measurement by the pathologist of a slide that contains thousands of muscle fibers - by definition, and individual pathologist's measurement will not be "reproducible" by another pathologist. We also know that the FDA's knee-jerk reactions in the past have turned out to be non-issues, so you combine these facts and you have to ask the following questions -
(1) What are the chances the FDA representative(s) that performed the lab review were experts in the methodology of measuring dystrophin-positive fibers? My guess is that very few hospitals and a limited number of pathologists actually perform these measurements and the ignorance the FDA has displayed in other aspects of DMD make it unlikely they had more than a rudimentary knowledge of the "methodology".
(2) Is this just a case of the FDA documenting that the test is subjective and the measurement so nuanced that no two pathologists would ever come up with the same result, without recognizing that the practical difference of one pathologist coming up with 25% and another coming up with 21% is really not significant (when the baseline levels are negligible)?
As CG stated in the conference call, they have four lab measurements that test for the presence/production of dystrophin and the FDA has only called into question the dystrophin-positive fiber measurement - the only one that is subjective. If measurements by 3 independent pathologists are (for example) 20%, 17% and 24%, they are still meaningful, even though they are not the same.
The FDA doesn't have to push RNA for all the ancillary data, because their primary data is conclusive - their drug is definitely toxic and failed to show efficacy in their primary analysis. It will be easy for the FDA to deny approval for Prosensa (or require further testing), but they don't have that luxury with Etep (or they will face the backlash of the DMD community), so they are delaying SRPT's filing as long as possible to let the Phase II data mature and the Phase III data to potentially show preliminary signs of efficacy.
Just going by their comments yesterday, where they hi-lited that the independent analysis will be done by three different readers - it seemed they were differentiating that from the original analysis, but I don't think they specifically said. It was obviously done by one hospital, but it would be surprising if there were different "methodologies" employed by pathologists in the same hospital?
It is difficult to understand what they mean by disparities in methodology when only one hospital and I believe one pathologist did all the readings? There is no indication that the FDA did their own fiber counts to uncover any disparities, so what on the surface, the statement makes absolutely no sense.
mauou - your post is irrational from the start - "The FDA is right ..no statistical significance" - The FDA has not made that determination and it is not relevant to the AA regulations. AA does not require statistical significance - only the "reasonable likelihood" of clinical benefit. The confirmatory trial is where statistical significance is determined. The only comparisons to natural history that were inaccurate were the ones done by the FDA, when they included younger boys and patients with Beckers MD. There are now several studies that breakout the natural history of boys by age and 6mWT at baseline and each of those show dramatically higher rates of decline over 96 weeks compared to the level of decline that the Etep-treated boys have experienced over 144 weeks. None of the issues raised by the FDA have anything to do with "statistics", so I'm not sure why you are so focused on them?
Truth - just doing a lot of venting. I really thought the pressure from the parents would keep the FDA in check, but it is clear they don't respond to pressure. The lab visit and reported dsystophin fiber methodology "disparities" is most telling - they visit in May, don't provide any formal feedback for 5 months and then blindside the company with "marked disparities" in the minutes, without providing any detail on what those disparities were? The lack of urgency and professionalism at the FDA is alarming.
How would I understand that - what do I care about the charities? Explain it to me - what exactly did he do to cause havoc and who at the FDA is using that as an excuse to hold this drug back?
Like I said - I could care less if he stays or go - I have invested in the science, not CG - but of all the bashing I have seen on this MB, I have yet to see one concrete example of what he did wrong or what he should have done differently. No doubt, he pushed for the AA because he believed the data (both clinical and surrogate) met the standards for AA. From then on, it has simply been a case of responding to the twists and turns of the FDA and throughout that time he has been nothing but transparent about what the SRPT has provided the FDA, what the FDA has asked of the company and what issues they have raised.
Don't expect a reversal by the FDA - there is no other explanation for their change in course except they wanted an additional 6 months to let the data mature from all the trials, so they could cover their butts, regardless of their decision. That may be a rational thing to do, but it goes completely against the grain of the AA regs and will cost many boys their lives and ability to function.
likeafox - listen to yourself - "he clearly angered someone at the FDA"? Even if it was true that he may have ruffled some feathers, is that an excuse for the FDA to play games with the approval process? Name one thing he has said or done publicly to disparage the FDA or would be a reason for someone to be #$%$. I've listened to every presentation and call and never heard him dis the FDA. When it comes to your "I don't have a clue" perception - the only times and issues I can recall him not having a clue is when the FDA has blindsided him and changed the rules without giving any detailed explanation. Take today's call for example - an analyst asked specifically what the FDA saw in their lab visit to claim "disparities" in the data - the FDA sprung that in the minutes without mentioning a word since their lab visit in May - how is he supposed to answer that? Same with the new requirement for safety data in the NDA - the FDA provided no explanation for the change in that requirement. Same with last year when they changed their stance after the RNA failure - no detail was provided on how they came to their decision.
I've seen the FDA screw companies before and they are the ultimate black box - they have no obligation to give an explanation for their decisions. The only thing a CEO can do is provide all the data and meet every request - do you have any examples of CG not doing that? I could care less if CG stays or goes, but I find it baffling that anyone that has listened to the calls over the past 3+ years can come to a conclusion other than the FDA has been completely clueless and irresponsible in how they have dealt with the SRPT AA issue. The fact that they opened the door in April after shutting it last year clearly shows they completely missed the boat on extrapolating the RNA failure and related natural history data to Etep. I also believe in the end this dystrophin issue will fall into the same camp.
grey - I agree with the sentiment, but let's not overstate. Assuming the FDA had closed the door on an AA after the initial 48-week data, it would have taken at least a year to get the PIII trial designed, approved and started. Also, if we have learned anything in the past few years, 48-week efficacy may not be concrete, simply because they don't start producing dystrophin until after week 12. So, best case we probably would be in the middle of a PIII trial right now with 48-week data pending. Regardless, the FDA has really made a mockery of the AA regs in this case - by the time they get approval in mid-2016 it will be 3 years after the initial P2 results, with at least a year and a half caused by FDA-created issues and delays.
Those are the word games the FDA uses to deflect criticism - i.e. Hamburg states publicly that they are working with the company to get the drug through the process as quickly as possible and then states the nebulous fact that they can't approve the drug until an NDA is filed. Meanwhile, the FDA employees set up roadblocks that delay SRPT's ability to file the NDA. You are completely correct - it is not right how this has unfolded.
Where do you come up with this cr@p - there is no such statement in the release. What was said on the conference call is no different than what was said in the past - the release of data from the 4th biopsy and the 168wk 6MWT will be subject to discussions with the FDA and the timing of the review. What amazes me is how CG continues to show respect to the FDA, when they continue to screw him over with these delays.
Can you point to one time he has lied or misled you about the FDA's position or the company's communications with the FDA. He has simply passed on in a very transparent way every communication that has taken place. Each setback that the company has encountered has been because of the FDA changing their stance on what they wanted - not because any deadline missed by the company or some data or issue uncovered by the FDA that the company had failed to disclose.
In a nutshell, the recent history is that the FDA reviewed their early data and said they would be open for an AA filing; then after Prosensa failed, they told SRPT that it may be premature because (1) the FDA thought the drugs were similar in efficacy and (2) the FDA thought the natural history data did not clearly show declines in SRPT's patient population - both of which ended up being false, so the FDA then came back and said they would be open to an AA filing by the end of the year, with the flexibility of the company being able to file additional safety and efficacy data during the review period. Now, the FDA is citing "marked disparities" in the methodology used for counting dystrophin positive fibers (but they provide no detail on what those disparities were or how they should be corrected in future analysis) and used that as excuse to force the filing date back. To me it smells like another case of the FDA not understanding the data/methodology and taking the natural bureaucratic reaction.
winter - everything you quoted is exactly the guidance the FDA provided the company up until they changed it last Friday with the most recent meeting minutes. The company knew the FDA was cloudy on the dystrophin data - that is why they were open to pushing for a 4th biopsy and having the original biopsy data independently reviewed - that was already in the works and going to be part of the post-submission review. How can you blame the CEO for the FDA changing the rules to force these items to be filed with the NDA?