- A group of advisers to the Food and Drug Administration urged the agency wait for more clinical trial results before approving an experimental cancer drug from biotech company Incyte, voting 13-4 on Thursday to recommend deferring a decision.
- The FDA isn't obligated to follow its advisers' recommendations, although it usually does. In this case, the agency appears to share its advisers' doubts about Incyte's application, laying out significant concerns in documents prepared for Thursday's meeting.
- Incyte is already running a larger study of its drug, for the treatment of metastatic anal cancer, and said in a statement it would work closely with the agency. If eventually approved, the drug, called retifanlimab, would be the eighth marketed cancer immunotherapy that works by blocking protein receptors known as PD-1 or PD-L1.
In April, the FDA convened the same advisory committee to review six accelerated approvals previously granted by the agency to cancer immunotherapies from Merck & Co., Roche and Bristol Myers Squibb. The three-day meeting was part of a broader review that had already led the three drugmakers, as well as AstraZeneca, to voluntarily withdraw four other immunotherapy indications.
In each case, confirmatory testing had not proven the clinical benefit needed to support the initial conditional clearance, spurring the FDA to reassess whether the drugs should remain on the market for those specific uses.
At the meeting, advisers often struggled to balance the negative clinical trial results against a desire to keep treatments available for patients with few other options. They ultimately favored keeping the drugs on the market for four of the six indications under consideration. For the other two, they recommended withdrawal and appeared swayed by commentary from Richard Pazdur, the FDA's top cancer drug evaluator.
One of the agency's underlying concerns is how well tumor response data in early testing of cancer immunotherapies translates into longer overall survival in larger trials. To date, the FDA has granted 35 accelerated approvals for a wide range of indications for drugs that block PD-1 or PD-L1. Thirty-one of those were based on overall response rate data and, in nine of those instances, subsequent testing did not support the initial approval.
In documents ahead of Thursday's meeting, the FDA outlined the same concern regarding use of Incyte's drug to treat advanced or metastatic squamous cell carcinoma of the anal canal. A Phase 2, single-arm study showed treatment led to tumor shrinkage in just 14% of the 94 patients who had enrolled and only half of those responses lasted more than six months.
"It is unclear whether the results of POD1UM-202 ... represent a reliable estimate of response and whether a response rate of 14% is reasonably likely to predict clinical benefit," FDA staff wrote in review documents, using Incyte's name for the study.
The agency's advisers appeared to agree, lengthening the odds of an accelerated approval for retifanlimab. The FDA is set to make its decision by July 25.