Replimune Panel Vote Shows How FDA Complete Response Letters and Resubmissions Work

Advisers to the US Food and Drug Administration voted 10 to 3 on July 30 that efficacy results from Replimune's IGNYTE study of RP1 (vusolimogene oderparepvec), given with nivolumab for advanced melanoma, were evaluable and clinically meaningful, the company said in a release read via BioSpace. BioPharma Dive reported that the agency is set to decide by Aug. 2, after twice turning the treatment back, and that agency scientists had argued the company did not clearly show it worked.

Those two earlier decisions were complete response letters. BioPharm International reported that FDA first declined to approve RP1 in July 2025, citing reliance on the single-arm IGNYTE trial without a control group, and that, according to Reuters, it raised similar concerns in a second rejection in April 2026. The panel's vote is advice; the decision remains FDA's.

What a complete response letter is

For biologics, the rule is 21 CFR 601.3. FDA sends a complete response letter “if the agency determines that it will not approve the biologics license application or supplement in its present form.” The letter is to describe all the deficiencies FDA has identified. If the agency decides after filing that the data are inadequate to support approval, it may issue the letter without first completing inspections, lot testing or labeling review. When possible, the letter recommends steps that would put the application in condition for approval.

The applicant then has two choices: resubmit, addressing all the deficiencies, or withdraw, which the regulation says is without prejudice to a later submission. If an applicant does neither within a year, FDA may treat the silence as a request to withdraw, though it will grant any reasonable request for more time.

How resubmissions are classified

FDA sorts resubmissions by how much review they need. Under its drug application rule, 21 CFR 314.110, a resubmission FDA classifies as Class 1 constitutes an agreement to start a new two-month review cycle from the date FDA receives it; a Class 2 resubmission starts a new six-month cycle.

Replimune said in a June 26 release filed with the Securities and Exchange Commission that FDA had accepted its latest BLA resubmission as a complete, Class 1 response with a goal date of Aug. 2, and had told the company to expect an advisory committee meeting in late July. BioPharma Dive reported that if FDA rejected RP1 again, the company would have to wait for results from a confirmatory trial, expected in late 2027, before resubmitting.

Why the letters are now public

Historically, the public learned about complete response letters mainly from companies. In July 2025, FDA published more than 200 such letters, issued between 2020 and 2024 for applications later approved, on openFDA, with trade secrets and confidential commercial information redacted. The agency said that a 2015 analysis by its researchers found sponsors “avoided mentioning 85% of the FDA’s concerns about safety and efficacy” when announcing that an application had not been approved.