Biotech Values

[iwfal]

SRPT -

Quote:
However, when we look at the relationship between percentage of dystrophin-positive fibers and mean change in the six-minute walk test (6MWT), there is no clear correlation between eteplirsen dose, percentage of dystrophin-positive fibers and 6MWT performance.


2) She misses the point here because she is asking one to one correlation between surrogate endpoint and final endpoint. The perfect example of this relationship between surrogate endpoint and final endpoint is ORR vs OS in oncology. Follow her logic, someone with PR definitely needs to show longer OS than someone with SD to make ORR as valid surrogate endpoint for OS. This is further from truth in reality. However unperfect correlationship between ORR and OS, it doesn't prevent FDA from giving accelerated approval by using ORR as surrogate endpoint for unmet medical needs in well defined patient population.

I would suggest her point is, overall, valid because the FDA generally wants proof of correlation. And without virtually 1:1 correlation with this small a set of patients it won't reach the level of 'proof'. (Note that I am not saying that 1:1 correlation is always required for a surrogate, only that the FDA probably wants proof of correlation and that is impossible to do in a trial this small unless the correlation is virtually perfect.)

More specifically:

1) the two 30 patients who could no longer complete the 6mwt appear to have had a very good dystrophin response (they, combined with the 2 continued 30 patients, had 52% increase at 48 weeks).

2) Two patients in the 30 group could no longer complete the 6mwt at 24 weeks, but no one in the placebo group had the same issue.

3) The 30 group had better dystrophin than the 50 group and yet worse 6mwt.

All told it will be interesting to see how the FDA treats this. My further comment - if I were the FDA, presented with partial data and with the company presenting only the good side of the data, I'd certainly want full access to the data before rejecting it. That said, I am not betting on that (or the opposite). Just exploring enough to understand the decision when it is made.

BTW - It will be interesting to see if the above items were just spurious bad luck. But it wouldn't completely surprise me if there were, for instance, an autoimmune issue that causes some patients to be harmed. Immunity issues have a tendency to crop up in odd (non-obvious) ways in replacement therapies (i.e. therapies that insert into the body complex, new-to-the-body, protein products).