Replimune Awaits FDA Direction After Complete Response Letter for Advanced Melanoma Therapy

On July 22, 2025, Replimune announced that the FDA issued a Complete Response Letter (CRL) for its Biologics License Application (BLA) seeking accelerated approval for RP1 (vusolimogene oderparepvec) in combination with nivolumab for advanced melanoma1234.

The FDA found the IGNYTE trial, which supported the application, to not be 'adequate and well-controlled,' citing that it failed to provide substantial evidence of effectiveness and could not be adequately interpreted due to heterogeneity in the patient population123.

The CRL did not identify any safety concerns with the therapy, but raised issues related to the design and clarity of the confirmatory phase 3 study, especially regarding the contribution of the individual components of the regimen1234.

Replimune expressed surprise and disappointment, stating that these issues had not been raised earlier in the review process and that the therapy had previously received breakthrough status based on its potential benefits34.

The company has announced plans to urgently request a Type A meeting with the FDA, expected within 30 days, in an effort to clarify requirements and explore a path forward for the possible accelerated approval of RP1 in this patient population, which has limited treatment options134.

Sources:

1. https://www.globenewswire.com/news-release/2025/07/22/3119299/0/en/Replimune-Receives-Complete-Response-Letter-from-FDA-for-RP1-Biologics-License-Application-for-the-Treatment-of-Advanced-Melanoma.html

2. https://www.fiercebiotech.com/biotech/replimunes-request-melanoma-approval-rejected-fda-cratering-stock

3. https://www.ajmc.com/view/fda-issues-crl-for-vusolimogene-oderparepvec-in-advanced-melanoma

4. https://www.pharmacytimes.com/view/fda-issues-crl-to-replimune-for-vusolimogene-oderparepvec-with-nivolumab-for-advnaced-melanoma