FDA Accepts Third RP1 BLA Resubmission for Advanced Melanoma

The FDA recently announced it has accepted Replimune Group's resubmitted Biologics License Application (BLA) for RP1 (vusolimogene oderparepvec) in combination with nivolumab for advanced melanoma, setting a Prescription Drug User Fee Act (PDUFA) goal date of August 2, 2026.¹ This marks the company's third BLA submission for RP1, following an initial complete response letter (CRL) in July 2025 and a second CRL in April 2026.^2,3 Replimune said the FDA views the matter as urgent and intends to prioritize the review.^¹

RP1's regulatory path has drawn attention amid broader concerns over inconsistent FDA decision-making during a period of agency leadership turnover.^⁴ Replimune said the agency has since signaled a more collaborative posture toward RP1 following recent changes in FDA leadership.^⁴ The company's stock rose nearly 80% on news of the planned third submission in May 2026.^⁴

The FDA classified the June 2026 submission as a complete, class 1 response and notified Replimune to expect an advisory committee meeting in late July, ahead of the August 2 PDUFA date.^¹ The resubmission seeks accelerated approval based on data from the phase 2 IGNYTE trial (NCT03767348).^²

Replimune first submitted the BLA for RP1 plus nivolumab in late 2024 and received an initial CRL on July 22, 2025.^2,3 The company's first resubmission was accepted by the FDA on October 20, 2025, with a PDUFA date of April 10, 2026, under a Class II review timeline.^³ The agency issued a second CRL on the same April 10, 2026 deadline, prompting the latest resubmission.^²

IGNYTE enrolled 140 patients with advanced melanoma who had confirmed progression on an anti-PD-1 containing regimen.^² Patients received RP1 in combination with nivolumab. According to Replimune, the regimen produced a 34% response rate with a median duration of response of 24.8 months.^²

Among responding patients, median progression-free survival was 30.6 months on RP1 plus nivolumab, compared with 4.4 months on patients' prior anti-PD-1 based regimen, according to data the company submitted to the FDA following its first CRL. RP1 holds breakthrough therapy designation and was granted priority review.^²

Regulatory History and Safety Profile of RP1 in Melanoma

Replimune disclosed in April 2026 a different FDA review team was assigned to evaluate the second resubmission, replacing the team previously involved with the company.^² According to Replimune, a senior member of the original review team stated publicly the clinical reviewers believed the company had provided adequate evidence of RP1's contribution of effect, but agency leadership disagreed.^² The company said the new review team did not meet with Replimune during the review process despite the company's request.^²

Replimune said the agency's April 2026 CRL contradicted positions the FDA had expressed during a September 2025 Type A meeting, including on the heterogeneity of the IGNYTE patient population and the feasibility of a randomized confirmatory study.^2,3 The company noted responses in IGNYTE were assessed using RECIST 1.1 without modification, per FDA request, and said analyses found no material difference in response rates between injected and non-injected lesions.^²

Replimune described RP1's safety profile in IGNYTE as favorable, though the company's releases do not specify adverse event rates.^² The company has run a global phase 3 confirmatory trial, IGNYTE-3, to satisfy the agency's accelerated approval requirements.^²

Sushil Patel, PhD, CEO of Replimune, commented on the FDA's posture toward the resubmitted application.

"We are pleased that the FDA has demonstrated urgency in reconsidering the RP1 BLA with an expeditious action date in recognition of the significant unmet need for advanced melanoma patients and support from the broader melanoma community," Patel said. "We look forward to a productive scientific and clinical discussion on the risk/benefit profile of RP1 in this difficult to treat setting."

Approximately half of patients with advanced melanoma do not respond to or progress after standard immune checkpoint blockade therapy, leaving a substantial population eligible for second-line options if RP1 is approved.^² An FDA advisory committee meeting is expected in late July 2026, ahead of the August 2 PDUFA date.^¹

References

1. Replimune announces FDA acceptance of RP1 biologics license application resubmission for advanced melanoma. News release. Replimune Group, Inc. June 26, 2026. Accessed June 26, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-rp1-biologics-license
2. Replimune receives complete response letter from the FDA for RP1 biologics license application for the treatment of advanced melanoma. News release. Replimune Group. April 10, 2026. Accessed June 26, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics-0/
3. Replimune announces FDA acceptance of BLA resubmission of RP1 for the treatment of advanced melanoma. News release. Replimune Group. October 20, 2025. Accessed June 26, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-bla-resubmission-rp1-0
4. Bell J. Replimune takes third swing at cancer drug approval following ‘productive’ FDA talks. BioPharma Dive. May 29, 2026. Accessed June 26, 2026. https://www.biopharmadive.com/news/replimune-fda-approval-application-talks-stock-biotech-melanoma/821496/

Frequently Asked Questions

What is RP1 being evaluated for?
RP1 (vusolimogene oderparepvec), in combination with nivolumab, is under FDA review for accelerated approval in advanced melanoma in patients with confirmed progression on prior anti-PD-1 therapy.

Why has RP1's BLA been resubmitted 3 times?
The FDA issued complete response letters in July 2025 and April 2026, both centered on disagreements over whether IGNYTE trial data adequately demonstrated RP1's contribution of effect when combined with nivolumab.

What did the IGNYTE trial show for RP1 plus nivolumab?
In the phase 2 IGNYTE trial, RP1 plus nivolumab produced a 34% response rate with a median duration of response of 24.8 months in patients with confirmed progression on anti-PD-1 therapy.