Replimune · RP1 · 2021 – 2024
What did the FDA tell Replimune before the BLA was filed?
The FDA's second letter and Replimune's 8-K quote the same 2021 and 2024 meetings, and each quotes a different part of them.
EphemerisX Research · Published · 2 source documents · 1 min read
Short answer
Both sides cite the same two meetings: a Type B meeting in March 2021 and a pre-BLA meeting in September 2024. The FDA's April 2026 letter quotes the concerns it raised there; Replimune's 8-K, filed three days later, quotes other parts of the same meetings.
What the evidence shows
According to the FDA's second letter, at the March 2021 Type B meeting the agency said that your proposed single-arm study will not enable identification of the contribution of each component of the combination to the overall response rate
FDA · Apr 10, 2026 · p. 3, and that it would not recommend that the Sponsor submit a BLA based on the results of a single-arm study
FDA · Apr 10, 2026 · p. 3.
Replimune's 8-K describes the same minutes: the FDA suggested in the March 2021 Type B minutes that if the data was sufficiently compelling, a single arm trial could be acceptable for consideration under accelerated approval
8-K · Apr 13, 2026.
On the September 2024 pre-BLA meeting, the letter quotes the FDA saying the company must provide evidence to demonstrate that there is a compelling reason that both RP1 and nivolumab are necessary to achieve the observed treatment effect
FDA · Apr 10, 2026 · p. 3. The 8-K quotes the same meeting: we do not object to your proposal to submit a BLA based primarily on data from the cohort of patients (n=140)
8-K · Apr 13, 2026.
On that point the documents agree. The letter says FDA ultimately did not object to the submission of the BLA
FDA · Apr 10, 2026 · p. 3, and that on review the study design concerns previously communicated were not addressed
FDA · Apr 10, 2026 · p. 3.
The letter also quotes a remark from the 2021 meeting: we consider the interpretation of responses in the setting of the intra-tumoral route of administration to be problematic in the lesions which have been injected
FDA · Apr 10, 2026 · p. 3. That subject returned in 2026: When did injected lesions become an FDA concern?
Not in this record: the minutes of either meeting.
Follow the thread
- Was the FDA's advice to Replimune consistent?The 2021 meeting, as the second letter quotes it
- When did injected lesions become an FDA concern?2021: responses in injected lesions “problematic”
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
- When is one trial enough? How the FDA weighed the evidence in three programsCross-investigation · Comparable evidence · with Aldeyra Therapeutics, Outlook Therapeutics
The documents, by date
The passages quoted
FDA Complete Response Letter, April 10, 2026 · page 3
your proposed single-arm study will not enable identification of the contribution of each component of the combination to the overall response rate” and we recommended that “you conduct a randomized controlled trial (RCT) to demonstrate efficacy and safety of the combination and isolate the contribution from each component to the overall treatment effect.”Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 3
Finally, we noted that “we consider the interpretation of responses in the setting of the intra-tumoral route of administration to be problematic in the lesions which have been injected.”Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 3
We also expressed concern about “potential issues of interpreting efficacy result due to baseline heterogeneities among study subjects” and reiterated that we “would not recommend that the Sponsor submit a BLA based on the results of a single-arm study”.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 3
FDA ultimately did not object to the submission of the BLA based on data from RPL-001-16, reflecting FDA’s flexibility in disease settings with high unmet need. However, on review of the RPL-001-16 data submitted to support the BLA, the study design concerns previously communicated were not addressed, and the contribution of vusolimogene oderparepvec to the observed response rate in RPL-001-16 could not be determined.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 3
Additionally, in the pre-BLA meeting dated September 3, 2024 (IND /Meeting ID 20461), we communicated that you must “provide evidence to demonstrate that there is a compelling reason that both RP1 and nivolumab are necessary to achieve the observed treatment effect.”Open at the source →
Replimune Form 8-K, filed April 13, 2026
While a randomized controlled trial was preferred, the FDA suggested in the March 2021 Type B minutes that if the data was sufficiently compelling, a single arm trial could be acceptable for consideration under accelerated approval. At the subsequent pre-BLA meeting, the FDA stated “we do not object to your proposal to submit a BLA based primarily on data from the cohort of patients (n=140) in the Phase 2 IGNYTE trial who had advanced melanoma and progressed while being treated with prior anti-PD-1 based therapy.”Open at the source →