Biotech Values

[iwfal]

While FDA may want 2-3yr RCT ... there is the ethical aspect of basically asking a fairly young age person to take 10% of their life in a trial possibly on placebo!

As I've noted before, you and I are on fundamentally opposite sides of this debate.

a) by implying that placebo patients are being harmed by being given placebo you are making the almost explicit assumption that the drug is more beneficial than harmful (and that the FDA's rules are arbitrary and capricious). I would point out that, as most on this board know, this is generally not the case - most drugs, even those with moderately good ph2s (a 'reasonable' post hoc), turn out to be more harmful than beneficial (they have meaningful AEs and fail their Ph3 efficacy endpoints).

b) you are effectively prioritizing the choice of the current patient over the harm to many years of future patients. There is not much doubt that as policy this will physically harm many more people more than it helps.

Note that I am not saying that there shouldn't be different standards for different diseases/drugs (see below link) - but I am saying that the standards shouldn't be based upon "need" since doing so will typically just hurt the very patients most "in need".

See #msg-117068869 for a way to do it - and further I'd be very surprised if the FDA wasn't effectively doing something like this.

As for the specific analysis of BMRN and SRPT:

It seems FDA is not even accepting the smaller studies as positive

Agreed that is the explicitly stated view in the FDA review - but note that the FDA reviews, particularly the statistician reviews, tend to be 'Devil's Advocate' positions. Like the practice of law there is an intentionally oppositional process, but don't mistake the process for the result - the FDA has approved a lot of drugs with explicitly negative statistician and medical reviews.

The lack of supportive secondary endpoints

I haven't looked at that yet.

It would seem even if FDA becomes accepting of some efficacy the review may still be delayed as you noted they still want to see other natural history data and it appears some other analysis (risk/benefit) are needed.

FWIW I am now on the fence about whether Dris should be approved. The new thrombocytopenia data (that the risk is not mitigatable because it is sudden onset without warning) is a big deal in my opinion. In order for me to decide which side of the fence I want to be on I'd want to understand better what the risks are for thrombo (e.g. how fast does it develop, how visible to a parent, how quickly treatable, mortality)