The Risk For Bristol

Bristol-Myers Squibb wants to dominate an emerging field of medicine that unleashes the immune system against tumors. Its melanoma drug ipilimumab is one of the stars of the American Society of Clinical Oncology meeting in Chicago.

“We intend to be at the leading edge” of the new field, says Bristol-Myers  chief scientific officer Elliott Sigal, speaking from his 31st story hotel room overlooking the sprawling convention center. “This is just the first step.” Bristol has more immune-boosting cancer drugs in early stages of testing, including one called PD1 antibody.

But getting the melanoma drug approved could prove surprisingly tricky. Its main trial included an unconventional control arm, which could raise eyes at the FDA. Instead of comparing Bristol’s ipilimumab to a placebo or to standard treatments (there are few options in melanoma), the trial compared ipilimumab to a vaccine called gp10o.  Patients who got ipilimumab lived longer.

The interpretation most melanoma researchers are making here is that ipilimumab is effective, and the vaccine essentially acted as a placebo.

But the  FDA may ask: How do researchers know that the vaccine is not toxic, and that this–not effects of ipilimumab–accounted for the difference in survival between the two patient groups?

“That is a credible scientific question. It is a question that I asked when I first saw the data: how do we know for sure that gp100 is not causing some [negative] change,” says  Sigal.

But he says the company has reviewed the data  carefully for any sign that the gp100 vaccine caused undue toxicity and found none. “We have pressure-tested this to my satisfaction. I am satisfied this is an adequate control.”

In a note, Leerink Swann analyst Seamus Fernandez called the survival improvement “impressive and consistent.” But he noted that the median survival of just 6.4 months in the control arm “was quite low and requires additional explanation.”

The ipilimumab drug–and immune therapy for cancer in general–has been controversial for years. But Sigal says he focused on it because Bristol had expertise in the area and because he believes bold new advances only come by taking calculated risks.

Sigal says he goes to  ASCO regularly becauses he likes to get first hand reports from doctors of how trials of the company’s drugs are going. Melanoma doctors’ enthusiasm for  ipilimumab was one one reason he kept pushing the drug forward even after it didn’t produce a high enough tumor shrinkage rate for early approval and a similar drug from Pfizer failed in a big trial. “When they say there is something different here, you listen,” he says.

One reason Bristol dropped $2.4 billion to buy  Medarex last year was that the company had a whole portfolio of immune-boosting drugs in early testing in addition ipilimumab, Sigal says. By combining multiple immune system drugs, Bristol hopes to get much stronger anti-cancer effects than any one drug could produce by itself.   “We are taking advantage of the fact that other companies have been relatively skeptical of immunotherapy,” says Bristol senior vice president Nils Lonberg. If ipilimumab makes it through the FDA, that will have been money well spent.