Is Merck KGaA Crazy? Or Just Crazy About Cancer Vaccines?

Merck KGaA's decision to start a Phase III trial in breast cancer with the therapeutic cancer vaccine Stimuvax begs the question: Has the German big pharma gone nuts?

First, Stimuvax hasn't been studied in breast cancer patients. Jumping into a 900-patient Phase III trial without testing the waters a bit in Phase II is risky, to say the least.

Second -- and this is the bigger head-scratcher -- the Phase II study that was done for Stimuvax in lung cancer failed.

To be fair, although the trial missed its primary endpoint of improving survival overall, a pre-stratified yet retrospective subset analysis of earlier-stage patients turned up an impressive survival benefit of 30.6 months for the vaccine-treated group compared to 13.3 months for the control group.

That subset analysis prompted Merck to initiate a Phase III trial of Stimuvax in earlier-stage lung cancer patients, which in itself is a bit risky considering that attempts to duplicate retrospective subset analyses haven't always panned out that well for biotechs in the past. Just ask cancer vaccine poster child Dendreon, which found what it thought was a good subset in its first Phase III trial of prostate cancer vaccine Provenge (sipuleucel-T) and tried to duplicate it in a second Phase III trial (which failed, and the subset turned out to be a red herring).

But then again, sometimes you work things out perfectly in Phase II so that all you have to do in Phase III is confirm exactly what you've already shown--and it still fails. Just look at Synta Pharmaceuticals and GlaxoSmithKline's recent Phase III failure with melanoma drug elesclomol despite what most folks considered excellent randomized Phase II data.

So maybe Merck said, "the heck with it â€" why spend a bunch of money and time on another Phase II lung cancer study. Let's gamble on the subset and go into Phase III."

Fine and dandy, but analysts predict the first interim look at that big Phase III lung cancer trial will come within a year, so why jump into a second Phase III in breast cancer before taking a peek at that? This seems like decidedly un-stodgy big pharma behavior. You might expect it from a biotech like Oncothyreon (formerly known as Biomira), which licensed Stimuvax to Merck back in 2001--but a conservative big pharma?

Maybe Dendreon's recent Phase III success with Provenge gave Merck an extra boost of confidence. Or maybe they felt things were moving too fast in the breast cancer field to wait an extra year for that Phase III lung data. Or maybe Merck's experts, with all the details in their hands, know something the rest of us don't.

In for a penny, in for a pound, I suppose.

Gambling Man photo by Flickr user waffler, CC2.0