Eli Lilly preps a familiar case for FDA review of a marginal cancer drug

On Thursday, a team from Eli Lilly ($LLY) will take the hot seats in front of an advisory committee meeting of external FDA experts to make a case for necitumumab, another cancer drug which offers only marginal efficacy for advanced patients with a troubling profile for potentially lethal adverse events. And their odds-on chance of succeeding helps explain why this field has become so popular with drug developers.

Lilly spelled out its data for necitumumab, a monoclonal antibody designed to fight squamous non-small cell lung cancer, in a press release tied to a study published in Lancet Oncology about a month ago. In their 1,093-patient Phase III trial, investigators tracked a median overall survival rate of 11.5 months for necitumumab and two chemotherapies compared to a 9.9-month OS rate for the chemo combo arm.

That 1.6-month advantage offers Lilly a chance to make the case that this drug would be a useful addition to oncologists' cache of cancer-fighting weapons, particularly as lung cancer has proved a tough target for developers over the years, with few new alternative treatments to pick from. Lilly also touted the "fully human" origin of its antibody, providing a shot at escaping some adverse events--though adding that there were more side effects in the drug arm compared to the control.

That kind of argument, coupled with cases of individuals who survived much longer than the median, has proven to be a regular winner at the FDA in recent times. Committee members have regularly pronounced themselves in need of new drugs to try, particularly for treatment-resistant patients. And the right kind of REMS, or risk mitigation strategy, can often satisfy any concerns about unnecessary patient suffering in pursuit of a better outcome.

This is also familiar territory for Lilly, which won an approval on Cyramza with a 6-week survival benefit. Lilly CEO John Lechleiter relishes the chance to defend its oncology turf. "I get irked when some well-meaning commentator says two months (OS) isn't much--they're probably not dying of cancer," he told the Financial Times in February.

The actual study in Lancet Oncology goes much deeper than the release, and highlights an area of vulnerability that Lilly will have to face during the review. During the study, 48% of the patients faced a serious adverse event, compared to the 38% in the chemo arm. And the deaths of 15 of the necitumumab group patients were linked to the drug, compared to 10 in the control group.

Any red flags, though, will come from the experts and the agency.

"Overall," Lilly noted in its review, "we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations."

"This is an improvement," says Fred Hirsch, an investigator at the University of Colorado Cancer Center and co-principal investigator for the study. "Based on this large prospective study in first-line therapy of squamous lung cancer, a subtype of lung cancer where there is an urgent unmet need for treatment improvement, the drug warrants approval."

For Lilly, which has promised investors three new drug approvals a year, the FDA panel's track record suggests that an improvement should be good enough for an FDA OK--unless advisers balk at the risks involved.

The FDA's internal review should be out Tuesday morning. And if history is a guide, it will offer the most skeptical profile of the drug. -- John Carroll (email | Twitter)

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