Here it is..................Matt Rosen
Highlights of $SRPT Dr. Temple #PPMDConnect speech from yesterday:
"Many cancer drugs are approved on what some would call a P1 study. When effects are dramatic, you certainly can do that."
"Safety databases for orphan drugs are often very small, in their 20s and 30s."
He lists a number of things specific for DMD.
1) Can't discuss any DMD drugs in pipeline.
2) "It's perfectly obvious from discussions that have gone around, apart from the issue of whether the production of a becker-type dystrophin will be an acceptable surrogate,not decided yet I'm not telling you anything one way or the other, for initial approvals, we will certainly consider such issues with respect to subsequent drugs for different genomic lesions, particularly rare ones, because success on a clinical endpoint might support that kind of surrogate endpoint, so that's something to keep in mind."
This bullet point concerns me somewhat and I'd like to hear people's opinions about it. Why would he have the "even if we don't, we still will" language unless they were considering not accepting dystrophin as a surrogate for Etep #AA? I might be reading too much into it but this is what concerned me (the only thing in the entire presentation).
3) #AA is for only clinically meaningful drugs; can't be used for marginal benefits even if people want it.
4) There is absolutely no required size for the study to support effectiveness. Often they are extremely small.
5) There is no particular reason to think large scale randomized trials will be needed for approval, especially if the drug works very well.
6) We need to be quite clear what risk/benefit really means. Long noted people with untreated illnesses will accept meaningful risk. Law doesn't allow approvals w/o meaningful data though.
7) We think variety of endpoints outside of 6MWT could be viable for approval.
End of prepared remarks: Q&A
Question on credible surrogate endpoint; how do you fi
My impression from listening to Dr. Temple's remarks, FWIW, is the other exons may well get approved very early via surrogate endpoint of dystophin being produced for that exon.
Also, his remarks about historical data being used instead of placebo--namely his comment to the effect that if one normally has a big downhill change in a year and a half but you show little decline in such a setting then that is an example of 'convincing evidence." No coincidence that the recent clinical 6MW etiplirsen results sound just like his example of "convincing." Made me think that a breakthrough designation, based on such clinical, "convincing" data might be the most expeditious FDA path for etiplirsen after all, perhaps obviating the need for accelerated approval. After reading the breakthrough descriptions from FDA, it seems it may be their new (from fidusia 2012) fastest path, maybe even faster than accelerated approval (which has been around for over 20 years).
But accelerated approval could make the other exons, and their much larger market, open to etiplirsen much much sooner, and from a stock/business standpoint, that makes SRPT value potential much higher.
Sentiment: Strong Buy
A few other thoughts.
If dystrophin production surrogate works to approve other exons, since it only takes 24 to 36 weeks of etiplirsen infusions to make a good % of dystrophin, then approval might occur less than six months after infusions start. If they began early next year, SRPT could have a hugely expanded market a year from now. Maybe they would have limitations on manufacturing, but then again, a lucrative market share just might intrigue even some of the bean-counter-laden big pharma, to the good of the boys and the business.
Again, regarding the etiplirsen clinical data, Dr. Temple referred to both historical and placebo controls as being valid; etiplirsen is using both, making efficient, elegent use of its data. The 'convincing" quote in the context of stability for a year and a half just keeps echoing in a positive way for etiplirsen, along with the 'no problem with small samples." Safety for etiplirsen isn't even an issue its so good. Chris has been saying the clinical data stands by itself, separate/independent from the surrogate dystrophin; Dr. Temple's above remarks certainly seemed aligned with Chris's, and by themselves support the clinically-based breakthrough designation-- especially with etiplirsen's spotless safety, 30 patient-years of which is complete about August 3rd 2013.
Sentiment: Strong Buy
Question on credible surrogate endpoint; how do you find it, especially in relation to DMD:
Answer: Numerous ways to make it credible, can be considerable judgment involved.
"Surrogate would be fibers are now coated w/ dystrophin, its becker like, could that be a surrogate? I'm not going to tell you the answer".
"No question that if a drug turns out to have a clinical benefit turns out can correlate it w/ a surrogate like dystrophin, that would become a surrogate for other exons later on. We're working on it. Diseases are more understood than they used to be".
"Over 20 years ago, people realized that boys w/ more dystrophin delayed by 2 years into a wheelchair. Boys w/ some dystrophin vs boys with no dystrophin. This was 20 years ago. How much are you expecting to see before you can say it's effective? Because here you have some of the chemistries given 25,35, 55% positive fibers, how effective does it have to be to approve?
Answer: "thats question for any surrogate? does 5% or getting to 30% matter? further question is does the location matter. whats the best way to measure it. cant give you the answers yet cause that will conceivably give you what we are or not gonna do, but we are asking those questions. "
question "if you can show 20, 30, 40% dystrophin its gotta show a benefit"
Answer: "more is certainty better. the question for some of these ,i dont know if that applies here, a lot of diseases if you replace the enzyme does it get to right place. that may not be as big of a problem here cause all is made in the muscle. those are the things being considered. the amount matters. can we show larger amounts of dystrophin correlates to clinical outcome? all of those things matter."
He comments about how he does not think a label will be restrictive to boys who are similarly aged to participants in the trials; ie, younger boy and older boys/men will be able to get the drug if its approved.
Those are the highlights but I would watch it
This all sounds positive to me. It's nice to hear them regurgitating what we've known for months. It does seem like they're playing around with ridiculous reasons NOT to allow Accelerated Approval - as if they're desperate to find something (or more likely just being VERY overly thorough). For example, Sarepta has shown a remarkable physical stability/improvement in these kids and clearly shown that each one has a large amount of a shortened "Becker-like" dystrophin in their muscles, as opposed to a longer, normal form of dystrophin - so if that's not an acceptable surrogate endpoint, then what the heck would they attribute the incredible outcome to?! Do they think tiny, magical elves happened to help these kids avoid wheelchairs exactly 24-weeks into each of them taking eteplirsen?
Even they have to admit, this Accelerated Approval business has taken too long. Their website says they attempt to respod within 60-days and that they have a 100% rate so far this year. Well, it was a long time before April 15 when they wanted more info, and it's been 2 1/2 months now since then! Meanwhile, GSK got their dangerous drug passed last week when they filed around mid-April. So what is really the hold-up here?