Replimune · RP1 · Apr 2026

How did Replimune's 8-K describe the FDA's second letter?

On each of the FDA's three deficiencies the 8-K states the company's position; it does not mention the early Phase 3 analysis.

EphemerisX Research · Published October 6, 2026 · 2 source documents · 1 min read

Short answer

On each of the FDA's three deficiencies, the company's 8-K states its own position. It does not mention the early Phase 3 analysis the letter called insufficient.

What the evidence shows

The letter says response rate and duration of response were not reliably assessed, could be artifactually increased, and may not be reproducible FDA · Apr 10, 2026 · p. 5. The 8-K says the company's analyses showed no material difference in response rates between injected and non-injected lesions 8-K · Apr 13, 2026. The letter says the response criteria were not consistent with RECIST v1.1 FDA · Apr 10, 2026 · p. 4; the 8-K says responses were assessed using RECIST 1.1 without modifications 8-K · Apr 13, 2026.

On the patient population, the letter cites the heterogeneity of the patient populations FDA · Apr 10, 2026 · p. 5; the 8-K says the agency did not raise further concerns about the heterogeneity of the patient population in IGNYTE 8-K · Apr 13, 2026 after the Type A meeting. On RP1's contribution, the letter says it remains unclear whether the observed responses in RPL-001-16 are due to nivolumab alone FDA · Apr 10, 2026 · p. 6; the 8-K says the company submitted a proposal for a descriptive analysis from IGNYTE-3 supporting contribution of components 8-K · Apr 13, 2026.

The 8-K does not mention the early, unplanned Phase 3 analysis submitted with the resubmission. 8-K · searched insufficient to support an efficacy claim FDA · Apr 10, 2026 · p. 4. And on the process, the letter says FDA advice has remained consistent FDA · Apr 10, 2026 · p. 1; the 8-K describes inconsistent communication 8-K · Apr 13, 2026.

Follow the thread

What did Replimune resubmit in October 2025, and what did the FDA make of it?The 8-K does not mention the early Phase 3 analysis
What did the FDA's second letter object to?Responses “not reliably assessed”
Was the FDA's advice to Replimune consistent?“Inconsistent communication”
When did injected lesions become an FDA concern?“No material difference” (8-K)

The documents, by date

The passages quoted

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.

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FDA Complete Response Letter, April 10, 2026 · page 4

This data is insufficient to support an efficacy claim.

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FDA Complete Response Letter, April 10, 2026 · page 4

In the Type A meeting dated September 16, 2025, FDA also communicated that the response criteria used in RPL-001-16 were not consistent with RECIST v1.1 and may not be comparable to response rates reported in the historical literature.

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FDA Complete Response Letter, April 10, 2026 · page 5

However, comparing response rates cross-trial from RPL-001-16 to historical controls is challenging due to the heterogeneity of the patient populations in RPL-001-16 and the historical controls (e.g., the type of prior therapy received, such as single agent anti-PD-1 or combination checkpoint inhibitor, duration of prior therapy, setting of prior anti-PD-1 therapy [adjuvant vs. advanced/metastatic setting], extent of disease at baseline).

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FDA Complete Response Letter, April 10, 2026 · page 5

Given these issues, the reported response rate and duration of response from RPL-001-16 were not reliably assessed, could be artifactually increased, and may not be reproducible.

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FDA Complete Response Letter, April 10, 2026 · page 6

Thus, it remains unclear whether the observed responses in RPL-001-16 are due to nivolumab alone.

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