A great story

Some years ago, one of my friends jokingly changed his last name from “Kim” to “Kim-ball” in honor of the movie The Fugitive, which was popular at the time. This movie — now 15 years old! — featured not only the “one-armed man” and Harrison Ford’s righteous innocence, but also the potential FDA approval of a fictional drug, “Provasic,” which was actually at the root of the plot.

Earlier in the week, there was a story in the ASCO daily e-mail news summary (a fantastic feature which I urge all of you to take advantage of) about “Provenge” (sipuleucel-T, Dendreon), not quite “Provasic” but with plenty of intrigue nonetheless. As you may know, Provenge is the name of a prostate cancer vaccine. Cancer vaccine research remains a fascinating area of study, as investigators continue to struggle mightily to harness the body’s immune system against invading cancer cells. The potential benefits of this research are tantalizing with almost mythic overtones. All of us know stories of certain patients whose apparently immunogenic tumors have spontaneously regressed, as if an internal triumph of good vs. evil. We hope that there will be successful vaccines that “use the body’s own natural defenses” to offer “personalized and individualized treatment.” There’s a lot riding on the success of these efforts, as the keys to this kingdom will unlock a goldmine.

Unfortunately, cancer vaccines haven’t met with a lot of success so far. GVAX (Cell Genesys), Canvaxin (CancerVax), and MyVax (Genitope), just to name a few, haven’t worked out in phase-3 trials in various disease types. I was just listening to one of Neil Love’s CDs, in which Dr. Brad Kahl discussed the disappointment in the recent follicular lymphoma cancer vaccine trial. He concluded by suggesting that young investigators might want to find other areas of research.

So could it be that a prostate cancer vaccine that actually works is just around the corner? Provenge actually ran two phase-3 studies a few years ago, D9901 and D9902A. Both failed to meet their primary endpoint and failed to achieve statistical significance for other endpoints. Combined, however, there was a suggestion that the results demonstrated a survival advantage. Naturally, the company wanted FDA approval on this basis. In 2007, an FDA advisory committee met, and the application was rejected — more data was sought. Two prominent oncologists had recommended against approval at that time and were subsequently targeted with death threats. At least one needed additional security for personal protection at the ASCO meeting. Though the spin was predictable — vulnerable cancer patients were upset at being denied life-saving treatments — other commentators later speculated that it was actually the stockholders who were the angriest, most vocal, and maybe most threatening group. Sounds a little bit like The Fugitive, doesn’t it?

So it was with interest that I read the recent ASCO e-mail bulletin. In it, I learned that the company announced that the most recent phase-3 results — ie, the additional data that the FDA had requested — was “positive.” Provenge stock subsequently soared, up 150% by the next day. There’s just one problem though — nobody knows the actual results yet. How much did patients benefit? What were the costs and toxicities? Was the methodology in the trial design and the reporting of the results sound? All of this awaits careful scrutiny of the upcoming abstract and publication, but none of it stands in the way of extraordinary excitement and rising share prices in the meantime. What pressure will there be on the FDA, and the experts voting for or against approval this time around? We’ll have to see how this movie ends.