FDA rejects Replimune’s oncolytic virus

Replimune had hoped that, with its oncolytic virus vusolimogene oderparepvec, it could challenge Iovance in post-PD-(L)1 melanoma, but the project has just been knocked back by the FDA.

According to Replimune, the agency said the phase 1/2 Ignyte trial, used to support the group's bid for accelerated approval,  wasn’t “adequate and well-controlled”. The FDA added that the trial also couldn’t be properly interpreted “due to the heterogeneity of the patient population”. The company said that no safety issues were raised.

However, there are questions about vuso-vec’s confirmatory trial, Ignyte-3. Replimune cited issues with that study’s design that “need to be addressed, including contribution of components”, without giving more details. Ignyte-3, which saw its first patient dosed in August, is testing vuso-vec plus Opdivo, versus physician’s choice of Opdualag, anti-PD-1 monotherapy, or chemo, in patients who’ve previously failed on anti-PD-1 and CTLA-4 therapy.

Notable vuso-vec trials

Source: OncologyPipeline & clinicaltrials.gov.

The company claimed the CRL raised issues not highlighted by the FDA during the mid and late-cycle reviews, and that it had aligned with the agency on Ignyte-3’s design. This raises the possibility that the agency has toughened up – something biotech has feared since Vinay Prasad was appointed head of the CBER division in May.

However, it’s hard to know without a direct communication from the FDA. The agency recently began publishing CRLs, but only for subsequently approved drugs. At the time, the FDA noted that sponsors often avoided mentioning FDA concerns about safety and efficacy, and sometimes didn’t disclose calls for new clinical trials.

Until the agency begins publishing CRLs in real time, this will remain a live issue.

The latest decision might be galling to Replimune investors after Iovance’s Amtagvi was approved on a single-arm trial that showed similar overall response rates to Ignyte – and Amtagvi was likely flattered by patient exclusions. However, Ignyte clearly has its own issues.

At last count, Replimune had $484m in cash, enough to get it into the fourth quarter of 2026. It’s unclear yet if there’s any future for vuso-vec; the group also has a follow-on project, RP2, in phase 2/3 in checkpoint inhibitor-naive uveal melanoma.

Replimune’s stock opened down 73% on Tuesday, while Iovance climbed 14% – still, the latter has problems of its own trying to sell Amtagvi.