Replimune · Nasdaq: REPL · RP1 (vusolimogene oderparepvec)

The documents give three response rates for three different populations: 34% in the company's April 8-K, a confirmed 32.9% in its 10-K, and 24.2% in the 91-patient efficacy population of the approval. Along the way, the FDA's second letter (April 10) questioned responses in patients without non-injected lesions, the advisory committee voted 10 to 3 (July 30), and the approval followed in August.

The company's April 2026 8-K says “patients with confirmed progression on an anti-PD-1 based regimen who received RP1 plus nivolumab had a 34% response rate” [8-K · Apr 13]; its 10-K says “The confirmed ORR was 32.9%” [10-K · Jun 29].

The approval 8-K reports “91 patients with at least one non-injected lesion included in the efficacy-evaluable population” [8-K · Aug 7], with “an objective response rate (ORR) of 24.2%” [8-K · Aug 7]. The three figures describe different populations.

On April 10, the FDA's second letter said “over half (53%) of patients with objective response did not have noninjected target lesions” [FDA · Apr 10 · p. 4], and that with those patients excluded the response rate “decreases markedly” [FDA · Apr 10 · p. 4]; the company's 8-K said its analyses showed “no material difference in response rates between injected and non-injected lesions” [8-K · Apr 13].

The advisory committee then “voted 10 to 3” [8-K · Jul 31] that the results are evaluable and clinically meaningful, and the approval 8-K reports “accelerated approval based on objective response rate and duration of response” [8-K · Aug 7].

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.

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 · 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]. The letter says the response criteria were “not consistent with RECIST v1.1” [FDA · Apr 10 · p. 4]; the 8-K says responses were assessed “using RECIST 1.1 without modifications” [8-K · Apr 13].

On the patient population, the letter cites the “heterogeneity of the patient populations” [FDA · Apr 10 · 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] 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 · 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].

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

One deficiency is new in the second letter: how tumor responses were assessed. Two concerns carried over, and the Phase 3 question moved from trial design to early data.

The first letter does not mention injected lesions, RECIST, surgery, biopsies or duration of response. [FDA · searched] The second says “over half (53%) of patients with objective response did not have noninjected target lesions” [FDA · Apr 10 · p. 4], and that at the September 2025 Type A meeting the FDA had communicated the response criteria were “not consistent with RECIST v1.1” [FDA · Apr 10 · p. 4].

Two concerns appear in both letters: the “heterogeneity of the RPL-001-16 trial patient population” [FDA · Jul 21 · p. 1] and that the trial was “not designed to isolate the contribution” [FDA · Jul 21 · p. 1] of RP1. On the Phase 3 trial, the first letter questioned the design (“single-agent chemotherapy options” [FDA · Jul 21 · p. 2] in the control arm); the second calls the early analysis submitted “insufficient to support an efficacy claim” [FDA · Apr 10 · p. 4].

The second letter also says “the review team members for this BLA resubmission were different” [FDA · Apr 10 · p. 1]. The company's 8-K says the agency “appears to have contradicted their positions expressed at the September 2025 Type A meeting” [8-K · Apr 13].

This record holds the company's account of the approval, not the FDA's: accelerated approval based on response rate and duration of response, in the 91 patients with a non-injected lesion, after the advisory committee voted 10 to 3. The FDA's approval letter and review are not in this record.

After the second letter, the 10-K says “the Company and the FDA aligned on a path forward for resubmission and reconsideration of the BLA” [10-K · Jun 29], and that “the FDA accepted the BLA resubmission as a Class 1 resubmission with an action date of August 2, 2026” [10-K · Jun 29].

The advisory committee discussed “whether the single-arm IGNYTE study, as designed and conducted, allows for a reliable determination of the expected response rate and durability of response in the proposed population” [8-K · Jul 31], and “voted 10 to 3” [8-K · Jul 31] on whether the results are evaluable and clinically meaningful.

The approval 8-K reports “accelerated approval based on objective response rate and duration of response” [8-K · Aug 7], in “91 patients with at least one non-injected lesion included in the efficacy-evaluable population” [8-K · Aug 7], and that “Continued approval for this indication may be contingent on verification of clinical benefit in a confirmatory trial(s)” [8-K · Aug 7].

The FDA's own reasoning, in its approval letter, review and label, is not in this record. [not in record]

Continued approval may depend on verifying clinical benefit in a confirmatory trial. The FDA's second letter called the early analysis of the Phase 3 trial insufficient, and that trial's results are not in this record.

The approval 8-K says “Continued approval for this indication may be contingent on verification of clinical benefit in a confirmatory trial(s)” [8-K · Aug 7].

The company's 10-K describes “the IGNYTE-3 trial” [10-K · Jun 29] as a randomized Phase 3. The FDA's second letter says the company submitted “an early unplanned analysis” [FDA · Apr 10 · p. 2] of the Phase 3 trial it names RP1-104, and that “This data is insufficient to support an efficacy claim” [FDA · Apr 10 · p. 4]. The FDA letters use only the name RP1-104 and the company's filings only IGNYTE-3; none of these documents uses both.

Not in this record: Phase 3 results, the FDA label, and Replimune's filings after August 7, 2026. [not in record]