Provenge, the Pazdur effect, and looking for a silver lining

Dendreon’s "approvable" letter for its cutting-edge prostate cancer vaccine Provenge this week asks for—among other things like further manufacturing specs—more clinical data, a request that sliced over 60% from the biotech’s market cap. (For more on Provenge’s rollercoaster background, see here and here.)

But why were Dendreon shares priced so high to begin with? An FDA advisory committee shocker in March, where FDA’s advisors voted 13-4 in favor of approving the vaccine. Indeed Provenge’s prospects for a positive ruling from the FDA panel looked slim going into that meeting: two Phase III studies supporting the application missed the primary endpoint target of time to progression as well as failing to meet secondary endpoints of clinical and pain progression and treatment failure.

And that’s not a good thing when you’re trying to prove you’ve got an effective product.

What won over the committee? Two things: First, an analysis of data from a subset of patients in one of the Phase III trials demonstrated a statistically significant increase in time to progression. Second, and perhaps as importantly, the review of the therapeutic vaccine falls under the purview of the agency’s Center for Biologic Evaluation & Research—not the Center for Drug Evaluation & Research’s Office of Oncology.

Provenge therefore avoided CDER’s Oncology Drugs Advisory Committee, which is now considered to be a stricter committee to go through because of the tone set by oncology director Richard Pazdur, MD.

One scenario that did not bode well for Provenge is the involvement of Pazdur himself in the review. When cancer drug reviews were organized under a newly created Office of Oncology in 2004, biologics and chemo-preventative drugs fell under the CDER office, while vaccines remained under the CBER umbrella. But Pazdur still has a hand in cancer vaccine reviews; for example, he consulted on the approval of Merck’s human papillomavirus vaccine Gardasil and has helped evaluate GSK’s competing HPV vaccine Cervarix.

Whether Pazdur is personally involved or not, FDA officials often say that they pay just as much attention to minority opinions as those in the majority when it comes to advisory committees. And the minority "no" opinions for Provenge were particularly unwavering.

It’s tough to say where Dendreon goes from here. Recovery from an FDA rejection can be agonizingly slow (see, for example, Xoma). Dendreon can at the very least hang its hat on the positive panel review as evidence of advocacy by a key body in the regulatory process. And the market potential for cancer vaccines—analysts expect it could grow to $6 billon by 2010--could dull the market effect of a negative FDA decision as investors hold firm with an eye toward the long-term possibilities.

Sanofi-Aventis’ recent acquisition of OxfordBiomedica’s renal cancer vaccine Trovax for approximately $700 million is hard evidence of interest in the field. That sustained interest could be Dendreon’s saving grace.