Benefits of Replimune's REPL.O skin cancer drug remain unclear due to flaws in the trial design that make it difficult to determine whether tumor shrinkage was driven by the drug or another therapy, FDA staff reviewers said in briefing documents released on Tuesday.
Shares of the company tumbled 31% in early trading.
Replimune is seeking approval for RP1 in combination with Bristol Myers Squibb's BMY.N immunotherapy Opdivo for the treatment of advanced melanoma, a highly aggressive form of skin cancer.
"The FDA review team concludes that this BLA (application) does not include an adequate and well-controlled investigation that demonstrates substantial evidence of effectiveness," the briefing documents said ahead of the staff's meeting set for Thursday.
Staff say response rates may be inflated
'ARTIFACTUALLY INFLATED' GOALS
The health regulator has previously asked Replimune to provide data from a well‑controlled trial demonstrating adequate evidence of effectiveness.
The single-arm study makes it difficult to know whether tumor shrinkage was caused by RP1 or Opdivo, staff said in the documents.
The FDA identified several issues with the application and criteria that were used for response assessment.
The review team concludes that these "artifactually" inflated the main goals of the trial and response rates, the staff said.
The staff added that the contribution of RP1 to the combination effect cannot be determined, and it is unclear if RP1 contributes to any observed effect.
Replimune submitted three-year survival data, but FDA staff reviewers said results from a trial lacking a randomized control group could not establish whether longer survival was due to the treatment rather than patient selection or other factors.
Regulator cites need for better-controlled data
The FDA declined to approve the drug for the second time in two years in April, citing reliance on a single-arm study without a control group, and asked for more data from a well-controlled trial demonstrating adequate evidence of the drug's effectiveness.
It was one of several contentious actions taken under then-Commissioner Marty Makary, who left the agency after a tumultuous stint that included high-profile disagreements with drugmakers.
Replimune did not immediately respond to a Reuters request for comment.
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