Biotech Values

[p3analyze]

>> Ipi BLA has a lot in common with DNDN’s original Provenge submission <<

Agreed. There are also differences.

BMS has many friends in the oncology community and in FDA. Unlike Provenge, there doesn't appear to be any Key opinion leader oncologists that will rear their ugly heads to openly challenge the ipilimumab BLA. THere certainly is no hedge fund poised to make billions from BMS's ipilimumab rejection so not much is at stake to worth a fight. They already had their share of set-back when FDA rejected their bid to file based on the 3 phase II pivotal studies. Over 2000 patients have been treated so far, all investigators seem to like the drug once they learned to cope with the grade 3 colitis and hyopit. It also has a relatively more robust clinical package- durable response have been demonstrated in the 3 pivotal phase II studies which also showed trend for improved survival when you consider the 0.03 mg ipi group as good as placebo in one of the studies. This 020 trial while not prospectively designed to study survival, was indeed amended in the last minute to call OS a primary endpoint, and does prove that ipilimumab monotherapy prolongs survival as long as one accepts gp100 is as good as placebo, regardless of what alpha spending function one wants to use.

So it's highly likely FDA will approve ipi on the first review cycle.

But it would not be surprising if FDA chooses to use BMS as fig leaf to pretend to uphold uniform regulatory standard by issuing a complete response letter. After all, this is a single-trial approval strategy (I know FDA has approved drugs based on a single trial), and the trial needs to be flawless executed.

That's a big question. There are so many moving parts

No SPA was in place, since all attention was devoted to the ongoing Phase III Ipi+DTIC vs DTIC alone.

It's almost certain this trial has been on the back-burner and clearly it appeared as if when Pien decided to sell MEDX, almost no value was given to this trial. It probably was run by CRO and FDA could audit the investigators who conducted the trial and there will almost certainly be 483 findings, and data issues.

The timing when the primary endpoint was changed to overall survival could be questioned. The sample size change is fair game too. The alpha spending function (between the primary and secondary comparison) was not explicitly stated, however much one would like to assume a nested hierarchy. The actual number of deaths appeared to exceed that planned in the statistical analysis plan as well, thus question can be raised whether the p-value would hold up in the ipi monotherapy arm under a sensitivity analysis at the planned number of events.

Finally justifying gp100 is as good as placebo is no easy task either.