Provenge Researcher Threatened for Questioning Company Studies

Provenge Researcher Threatened for Questioning Company Studies

April 2nd, 2012 // 1:00 pm @ jmpickett

Source: Pharmalot

Yet another controversy surrounding the Provenge prostate cancer vaccine has emerged. The latest involves Marie Huber, a former hedge fund manager who recently co-authored a medical study that questioned the benefit of the medicine and, as a result, has received threatening remarks on investor message boards.

Why? Her thesis is that the studies used to win FDA approval were flawed. In her view, the main reason Provenge was deemed to extend survival was that older men who did not receive the treatment died months sooner than other patients in other studies. This is because the placebo they received was harmful and made Provenge appear better by comparison.

“Overall, we believe that a detrimental effect of the placebo intervention is at least as plausible as a beneficial effect of sipuleucel-T as an explanation of the survival difference observed in the IMPACT trial,” Huber and her co-authors wrote in their January paper in the Journal of the National Cancer Institute. Spiluleucel-T is Provenge, by the way (here is the paper).

As far as Huber is concerned, Provenge may be harming patients who are treated with the vaccine. “The whole thing is utterly horrific,” she tells Reuters, which ran an insightful article on the latest dust-up. “The company got away with hiding data and doctors making $7,000 per prescription won’t even engage in discussion” about whether the vaccines helps patients.

After the study ran, however, some vitriol was directed her way. A post on an investor message board last month suggested “somebody smack her with a rubber hose,” according to Reuters, which did not mention which message board contained the missive. And an email she received contained this message: “Don’t think you will be unscathed in this battle you waged on Provenge.” Huber, by the way, describes herself as an independent scientist and did not declare any financial conflicts.

Of course, investor boards often contain unflattering remarks, and worse, aimed at individuals who they believe will alter their profit-making prospects. This is not the first time, though, that this theory has been raised. An editorial in The New England Journal of Medicine questioned whether the treatment regimen given the placebo group in the IMPACT study produced a favorable result (read this).

Provenge has always generated strong sentiments. Doctors who raised doubts about the vaccine claimed to have received threats while attending a cancer meeting five years ago (back story) and patients and investors regularly protested at FDA offices before approval was given in 2011 (see here).

All this heat came about after an unexpected FDA delay in approving Provenge occurred amid alleged conflicts of interest involving two members of an agency advisory committee. They quietly wrote FDA officials to veto a panel recommendation in favor of approval (read here). The FDA delayed endorsing the vaccine, further fueling a debate about the use and approval of experimental meds.

“Provenge came along when we didn’t have much to offer for prostate cancer,” Len Lichtenfeld of the American Cancer Society tells Reuters. “The advocacy community was bursting at the seams for something that worked. When you have that situation, it inflames passions and that can overtake the science.”

As Reuters notes, Provenge was based on the idea that a patient’s immune system can be harnessed to combat cancer and this was the first such vaccine to reach the market. However, there have been skeptics who have questioned not only questioned the key Provenge study – in which the placebo group received cells not incubated with an immune stimulant – but also the added median survival time of four months.

There has also been debate about effectiveness because Provenge does not shrink tumors., Steven Rosenberg of the National Cancer Institute tells Reuters this raised doubts over whether Provenge helps patients live longer, as the IMPACT trial reported. But Mark Frohlich, Dendreon’s chief medical officer, tells the news service “we have a lot of data that supports the idea that the product works the way it was designed to. We’re seeing evidence of immune-system activation. The only question is whether the T cells are killing the tumor.”

The rest of the Reuters story, which you can read here, offers additional detail on the Huber analysis – both pro and con. To what extent this debate will matter is unclear. More recently, Provenge sales have been disappointing due, in part, to miscues informing doctors last year about reimbursement and the prospects for a rival med called Zytiga from Johnson & Johnson (see here and here).

Meanwhile, shares in Dendreon, which sells Provenge, continue to gyrate wildly.

[UPDATE: On Friday night ET, a Dendreon spokeswoman sent us a note to say: “The FDA approval was based on a significant improvement in overall survival shown in three well-designed, randomized, double-blind, controlled clinical trials – including the pivotal IMPACT trial – with remarkably consistent results shown across the trials as well as in numerous patient subgroups.

The Provenge clinical data have undergone a rigorous scientific review process that included FDA review process, a Center for Medicare and Medicaid Services national coverage determination, a Technology Assessment and the peer review of multiple publications. As evidenced by the FDA approval, CMS national coverage decision, and NCCN treatment guidelines, the PROVENGE data clearly demonstrated a significant patient survival benefit and support its use as a clinically meaningful treatment option for certain types of advanced prostate cancer.”]