Replimune · RP1 · 2021 – 2026
Was the FDA's advice to Replimune consistent?
The FDA's letter says it was, citing communications back to 2021. Replimune's filings say it was not, citing the mid- and late-cycle reviews and the September 2025 meeting.
EphemerisX Research · Published · 4 source documents · 1 min read
Short answer
The two sides answer differently. The FDA's second letter points to its communications from March 2021 onward; Replimune's 8-Ks and 10-K point to the mid- and late-cycle reviews and the September 2025 Type A meeting.
What the evidence shows
The FDA's second letter: FDA advice has remained consistent
FDA · Apr 10, 2026 · p. 1, and FDA clearly communicated our concerns with the study design in multiple FDA interactions throughout your development program
FDA · Apr 10, 2026 · p. 3. It quotes the 2021 meeting: the agency 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, July 2025: The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews
8-K · Jul 22, 2025. April 2026: the agency appears to have contradicted their positions expressed at the September 2025 Type A meeting
8-K · Apr 13, 2026, and the process involved inconsistent communication
8-K · Apr 13, 2026.
Both sides record that the resubmission was accepted as complete. The letter: the amendment constituted a complete response to our July 21, 2025, action letter
FDA · Apr 10, 2026 · p. 1. The 8-K: The company requested feedback, however, the FDA did not respond and subsequently accepted the resubmission as a complete response to the July 2025 CRL
8-K · Apr 13, 2026. The 10-K: The second CRL reiterated points made in the first CRL that were presumably addressed by the FDA accepting the BLA for resubmission
10-K · Jun 29, 2026.
Not in this record: the minutes of the 2021, 2024 and 2025 meetings that both sides cite.
Follow the thread
- What did the FDA tell Replimune before the BLA was filed?The 2021 meeting, as the second letter quotes it
- How did Replimune describe the first letter?“Not raised” in the mid- and late-cycle reviews
- What was said at the September 2025 Type A meeting?“Appears to have contradicted” the meeting
- How did Replimune's 8-K describe the FDA's second letter?“Inconsistent communication”
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
The documents, by date
The passages quoted
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 →
FDA Complete Response Letter, April 10, 2026 · page 1
FDA advice has remained consistent as evidenced by our communications dating back to March 2021 and subsequent interactions described in this letter.Open at the source →
FDA Complete Response Letter, April 10, 2026 · page 1
We acknowledge receipt of your amendment dated October 9, 2025, which constituted a complete response to our July 21, 2025, action letter.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 clearly communicated our concerns with the study design in multiple FDA interactions throughout your development program.Open at the source →
Replimune Form 8-K, filed April 13, 2026
In the CRL, the agency appears to have contradicted their positions expressed at the September 2025 Type A meeting, including on the following points:Open at the source →
Replimune Form 8-K, filed April 13, 2026
The company requested feedback, however, the FDA did not respond and subsequently accepted the resubmission as a complete response to the July 2025 CRL.Open at the source →
Replimune Form 8-K, filed April 13, 2026
All of it was met with inconsistent communication and a fragmented and slow-moving regulatory process which clearly puts U.S. innovation at riskOpen at the source →
Replimune Form 10-K, filed June 29, 2026
The second CRL reiterated points made in the first CRL that were presumably addressed by the FDA accepting the BLA for resubmission indicating the resubmission was a complete response to the initial CRL. The second CRL also reverses on points the FDA made in the September 2025 Type A meeting following the initial CRL.Open at the source →