An FDA advisory panel offered some key though largely lukewarm support for Eli Lilly's ($LLY) experimental lung cancer drug necitumumab. While there was no formal vote for or against approval, committee members weighed the positives and negatives of a drug that showed only a marginal survival advantage for patients--but a big enough plus for patients that has warranted approvals in the past. And on balance, most supported an approval for Lilly during a roundtable discussion.
Eli Lilly's cancer drug is testing the FDA's appetite for marginally effective oncology therapies linked with serious adverse events. Lilly was forced to halt one study for necitumumab due to an alarming rise of deaths due to blood clots and came up with only a 1.6-month overall survival benefit in the final, pivotal study. The progression-free survival advantage for squamous non-small cell lung cancer was measured in weeks; 5.7 months versus 5.5 months. And there were only a relatively small number of Americans in the study, troubling to some.
Nevertheless, a majority of the committee members was clearly supportive of the drug's approval, giving doctors an extra option for treating a disease that kills most patients within 5 years.
"Certainly we want to have options," noted Michael Menefee, agreeing with one of his colleagues on the panel, "but better options." If there was a three- to 6-month advantage, he added, this would be an easier discussion. But "1.6 months is commensurate with other drugs approved."
"Yes there is a positive benefit-risk ratio to this compound," Menefee concluded, "but there are caveats out there regarding toxicity and the magnitude of the overall benefit."
Looking at more study data before making a formal marketing decision, he said, "may be worthwhile."
"This may be a very temporary move forward," said Deborah Armstrong, an oncologist at Johns Hopkins and chairperson for the committee, but it could help fill the void for patients. "The survival benefit is modest but it is real."
That kind of argument 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.
Bernstein's Tim Anderson, who enjoys countering the naysayers when it comes to Lilly, ambitiously projected a $770 million peak sales estimate on necitumumab, way ahead of the $450 million consensus. "In our view," he wrote, "the FDA seemed comfortable with the idea of approving the drug, and wanted simply to ask the panel's opinion on whether proposed safety warnings in the label intended to limit the risk around hypomagnesemia (a toxicity associated with the anti-EGFR class of drugs) and thromboembolic events would suffice to guide physicians and patients. In its briefing, LLY defended the benefit and acknowledged the risks, showing a clear willingness to work with the FDA on appropriate labeling, post-marketing surveillance and Phase IV studies to improve necitumumab's safety."
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 agency was more interested in the expert discussion than in a vote, FDA cancer czar Richard Pazdur told the group today. Next stop: The FDA will make a formal decision by the regulatory deadline, he added, "so, stay tuned."