Replimune · RP1 · Jul 2025
How did Replimune describe the first letter?
The 8-K reported the letter's two reasons, said the issues had not been raised in the mid- and late-cycle reviews, and said RP1 would not be viable without accelerated approval.
EphemerisX Research · Published · 2 source documents · 1 min read
Short answer
Replimune's 8-K of July 22, 2025 reports the letter's two reasons in close to the letter's own words. It adds three statements of its own: the issues were not raised earlier in the review, the confirmatory study design had been agreed, and RP1's development would not be viable without timely accelerated approval.
What the evidence shows
The 8-K says the FDA said the trial cannot be adequately interpreted due to the heterogeneity of the patient population
8-K · Jul 22, 2025 and raised items related to the confirmatory trial study design which need to be addressed, including contribution of components
8-K · Jul 22, 2025. The letter's own words: heterogeneity of the RPL-001-16 trial patient population
FDA · Jul 21, 2025 · p. 1, and a trial not designed to isolate the contribution
FDA · Jul 21, 2025 · p. 1 of RP1.
The CEO is quoted: The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews
8-K · Jul 22, 2025, and we had also aligned on the design of the confirmatory study
8-K · Jul 22, 2025. The letter's additional comments list Several issues that must be addressed
FDA · Jul 21, 2025 · p. 2 with the Phase 3 trial it names RP1-104.
The 8-K says the company would seek timely accelerated approval of RP1 without which the development of RP1 for advanced cancer patients with limited options will not be viable
8-K · Jul 22, 2025. It said so again in September 2025 and April 2026: What happened to the confirmatory trial Replimune said would not be viable?
It also says no safety issues were raised
8-K · Jul 22, 2025; the letter's deficiency concerns effectiveness.
Follow the thread
- What did the FDA's first letter object to?The letter's reasons, in the 8-K
- What happened to the confirmatory trial Replimune said would not be viable?“Will not be viable”
- Was the FDA's advice to Replimune consistent?“Not raised” in the mid- and late-cycle reviews
This investigation connects to
- When is one trial enough? How the FDA weighed the evidence in three programsCross-investigation · Comparable evidence · with Aldeyra Therapeutics, Outlook Therapeutics
- What did “no efficacy or safety issues” cover in these FDA letter announcements?Cross-investigation · Shared concern · with CorMedix, Verrica Pharmaceuticals
The documents, by date
The passages quoted
FDA Complete Response Letter, July 21, 2025 · page 1
The RPL-001-16 trial was also not designed to isolate the contribution of vusolimogene oderparepvec to the observed ORR when administered in combination with nivolumab.Open at the source →
FDA Complete Response Letter, July 21, 2025 · page 1
However, the numerically higher response rate cannot be adequately interpreted due to heterogeneity of the RPL-001-16 trial patient population, including the type of prior therapy received, such as single agent anti-PD-1 or combination checkpoint inhibitor, duration and setting of prior anti-PD-1 therapy, and extent of disease at baseline, and due to the heterogeneity of the patient population reported in the literature.Open at the source →
FDA Complete Response Letter, July 21, 2025 · page 2
Several issues that must be addressed have been identified with the RP1-104 trial, which is a Phase 3 multicenter, multiregional, randomized, controlled, open-label trial to evaluate the safety and efficacy of vusolimogene oderparepvec in combination with nivolumab compared with treatment of physician’s choice in patients with unresectable advanced cutaneous melanoma who have confirmed disease progression on an anti-PD-1 and an anti-CTLA-4 treatment regime, either in combination or in sequence.Open at the source →
Replimune Form 8-K, filed July 22, 2025
The CRL indicates that the FDA is unable to approve the application in its present form. The FDA has indicated that the IGNYTE trial is not considered to be an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness. Furthermore, the FDA said the trial cannot be adequately interpreted due to the heterogeneity of the patient population. The CRL also states that there are items related to the confirmatory trial study design which need to be addressed, including contribution of components. Importantly, no safety issues were raised.Open at the source →
Replimune Form 8-K, filed July 22, 2025
The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study.Open at the source →
Replimune Form 8-K, filed July 22, 2025
Replimune plans to urgently interact with the FDA to find a path forward for the timely accelerated approval of RP1 without which the development of RP1 for advanced cancer patients with limited options will not be viable.Open at the source →