Replimune · RP1 · Oct 2025
What did Replimune resubmit in October 2025, and what did the FDA make of it?
An early look at 40 patients in the Phase 3 trial and new analyses of the single-arm trial. The FDA set an action date of April 10, 2026, the date of the second letter.
EphemerisX Research · Published · 3 source documents · 1 min read
Short answer
The resubmission added an early, unplanned analysis of the Phase 3 trial (22 patients on RP1 with nivolumab, 18 on the control arm, 10% of planned enrollment) and exploratory analyses of the single-arm trial. The FDA set an action date of April 10, 2026, and issued its second letter that day.
What the evidence shows
In October 2025 the company said Additional information, data and analyses were included in the resubmission
8-K · Oct 20, 2025, and that The PDUFA date set by the FDA is April 10, 2026 based on a Class II resubmission timeline
8-K · Oct 20, 2025.
The second letter lists them: ORR data from an early unplanned analysis from your ongoing, randomized, Phase 3 trial, RP1-104
FDA · Apr 10, 2026 · p. 2, representing 10% of the planned enrollment of 400 patients
FDA · Apr 10, 2026 · p. 2, and exploratory analyses of progression-free survival, and of response in patients who had both injected and non-injected tumors
FDA · Apr 10, 2026 · p. 2.
The letter places it after the Type A meeting: Instead, you submitted data from an early unplanned analysis from RP1-104
FDA · Apr 10, 2026 · p. 4. On the Phase 3 data it lists Limited number of patients treated to date (10% of the planned study population)
FDA · Apr 10, 2026 · p. 2, Response assessment performed only by investigator
FDA · Apr 10, 2026 · p. 2 and Lack of duration of response data
FDA · Apr 10, 2026 · p. 2, and concludes: This data is insufficient to support an efficacy claim
FDA · Apr 10, 2026 · p. 4. The exploratory analyses do not alter our initial conclusion
FDA · Apr 10, 2026 · p. 2.
Replimune's April 2026 8-K cites one of those analyses: median progression free survival on RP1 plus nivolumab was 30.6 months compared to 4.4 months on their prior PD-1 based regimen
8-K · Apr 13, 2026. The 8-K does not mention the early, unplanned Phase 3 analysis submitted with the resubmission. 8-K · searched
Follow the thread
- What was said at the September 2025 Type A meeting?“Instead, you submitted” an early Phase 3 analysis
- What did the FDA's second letter object to?Phase 3 data “insufficient”
- How did Replimune's 8-K describe the FDA's second letter?The 8-K does not mention the early Phase 3 analysis
- How did RP1 go from a second FDA letter to accelerated approval in four months?Class II resubmission, then Class 1
This investigation connects to
- How did two programs move forward after repeat FDA letters without running a new trial?Cross-investigation · Comparable evidence · with Outlook Therapeutics
- What is a Class 1 or Class 2 resubmission, and how did each play out in these records?Cross-investigation · Regulatory pathway · with Aldeyra Therapeutics, CorMedix, Outlook Therapeutics
The documents, by date
The passages quoted
Replimune Form 8-K, filed October 20, 2025
The PDUFA date set by the FDA is April 10, 2026 based on a Class II resubmission timeline.Open at the source →
Replimune Form 8-K, filed October 20, 2025
Additional information, data and analyses were included in the resubmission which will be part of the BLA review. The FDA indicated this resubmission is considered to be a complete response to the complete response letter received in July 2025.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 2
You also provided results from additional exploratory analyses of RPL-001-16, including analyses of patients who had a response to immediate prior anti-PD1 therapy and their subsequent response to the combination of vusolimogene oderparepvec and nivolumab, of progression-free survival, and of response in patients who had both injected and non-injected tumors.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 2
Therefore, the evidence as presented does not meet the evidentiary standards required for regulatory approval, and the results of the additional exploratory analyses of the RPL-001-16 data do not alter our initial conclusion that the RPL-001-16 trial is not an adequate and well-controlled clinical investigation that demonstrates substantial evidence of effectiveness.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 2
To support resubmission of the BLA on October 9, 2025, you provided ORR data from an early unplanned analysis from your ongoing, randomized, Phase 3 trial, RP1-104, including 22 patients in the investigational arm of vusolimogene oderparepvec with nivolumab and 18 patients in the control arm (physician’s choice of treatment), representing 10% of the planned enrollment of 400 patients.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 2
For RP1-104 • Limited number of patients treated to date (10% of the planned study population) • Response assessment performed only by investigator, • Lack of duration of response data, and • Difficulty in interpreting progression-free survival data due to lack of pre-specification for this analysis and without adequate type 1 error control.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 4
Instead, you submitted data from an early unplanned analysis from RP1-104, representing 10% of the planned enrollment, as well as additional exploratory analyses of the RPL-001-16 data, to support BLA resubmission. This data is insufficient to support an efficacy claim.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 4
This data is insufficient to support an efficacy claim.Open at the source →
Replimune Form 8-K, filed April 13, 2026
The 8-K does not mention the early, unplanned Phase 3 analysis submitted with the resubmission.
Open the document →Replimune Form 8-K, filed April 13, 2026
The company also included data from IGNYTE showing median progression free survival on RP1 plus nivolumab was 30.6 months compared to 4.4 months on their prior PD-1 based regimen.Open at the source →