Biotech Values

[terry hallinan]

DewDiligence - Interim Looks,

If the p-value allocated to an interim look is minuscule—as is supposedly the case for GTOP—then missing the trigger for full-fledged unblinding is not bearish to any material degree.

If, on the other hand, a sizable amount of p-value is allocated to an interim look—as was the case, for instance, with BIOM’s Theratope trial a few years ago—then missing the unblinding trigger is indeed bearish. (You’ll recall that BIOM sold off precipitously after the first interim miss.)

But, of course, so did GTOP.

This is no more than simple arithmetic. Missing an interim look with a sizable p-value allocation reduces the likelihood that the drug has truly compelling efficacy. Not only does this lower the probability of hitting the final endpoint (or subsequent interim endpoints), it may also call into question the commercial viability of the drug.

Few marketed drugs have had trials unblinded early.

There are cases where drug trials have been unblinded early and then the drug failed to gain approval.

Eli Lilly breathed a huge sigh of relief when Xigris got approval by the full FDA panel after failing to get a recommendation from the expert panel.

Most anybody here probably knows more than I do about the matter but I don't think Xigris has had rousing sales.

These days, most sponsors are smart enough to avert the kind of mistake that BIOM made: either they don’t schedule interim looks at all, or they allocate only tiny amounts of p-value to them.

BIOM's most calamitous blunder IMHO was "improving" the prospects for the pivotal trial by profiling "weller" patients than the ones they were successful with in the preliminary trials. The theory that sicker patients are less able to benefit from cancer vaccines is - ahh, ummm - a theory. There is contradictory evidence with the proviso that one has to account for the induction period.

The decision to profile patients with less advanced cancers led to a very long trial and introduction of a huge area of uncertainty after women were advised their breast cancers had advanced and to seek other therapy of their and their doctor's choosing.

I am not denying at all that the hefty allocation of p-value (some very dubious math involved BTW) to the interim look was a bum decision like much of the design.

Bad management will do it to you regularly.

That is what I find most scary in SCLN's pivotal trial in HCV scheduled for topline results to be presented next month. The widely acclaimed CMO found other employment.

JMO.

Best, Terry