Biotech Values

[ghmm]

BMRN:

On the leerink call they said they have additional data (post hoc) which they haven't shared (some for competitive reasons) which they believe further strengthens the case for drisapersen.

Certainly the failed ph 3 is an issue. But there was actually an almost positive subset analysis - the patients enrolled at the same trial centers used in the phase 2s. In any case a failed phase 3 is not a proof of inefficacy, unless it was strongly the other way (I'm ignoring post hoc issues). So the p value in the ph2s are hard to explain away unless you think there was cheating/bias.

I'd suggest the big loss in the failed ph3 is that you get less of what you ordinarily get in this situation - a better understanding of the subgroups that work, how well it works, and the true clinical robustness of the treatment. And without that data care providers and patients will make less optimal decisions about treatment.

Altogether the failed ph3 matters a lot. I'd just suggest not a complete deal killer?

InterMune's CAPACITY 1 trial was a good example of P3 that showed no benefit and yet the drug was later shown to have efficacy. I actually like this comparison in a few ways
1. Both diseases are not completely well understood and finding the "right" patients to show progression in a relatively short duration trial was/is challenging.
2. I also believe the efficacy of both driseapersen and eteplirsen is small (much like Pirfenidone in IPF).
3. The diseases are dire with a great unmet need that I believe the hurdle for accelerated approval will be fairly low. With driseapersen and eteplirsen a very active/vocal patient community and the disease effecting young boys IMO help lower the threshold for approval.

I certainly agree it is setting a bad science precedent - and risks patients going forward (see my later comment on ph 3 failure)

I don't see it quite this way. As jq and BMRN have pointed out there are cases where a drug has failed Phase 3 (granted the data was more robust) been approved anyway and today its fairly obvious of the benefit especially when given earlier/over a much longer period then the trial. Here the risks/benefit given the nature of the disease seems to clearly favor attempting the therapy.

PTC may potentially unblinding their trial before Dris or Etep are approved and if PTCs ph3 is positive it might add more doubt to Dris thesis.

Right or wrong, I actually think the street would get scared by a PTC failure as it would cast broad doubts on the ability to show a treatment benefit in a more robust DMD study and likely further question the understanding of the disease.