The decision affects Replimune’s lead product candidate, which is based on a genetically engineered herpes simplex virus intended to stimulate an anti-tumour immune response.
During the IGNYTE trial, patients treated with RP1 plus nivolumab showed a 34% response rate and a median duration of 24.8 months, with a favourable safety profile.
Replimune contends these results warrant making the therapy accessible to cancer patients with advanced stages of the disease.
The company noted that the FDA indicated a change in the review team involved in the resubmission, a decision that deviated from the September 2025 Type A meeting discussions.
Replimune CEO Sushil Patel said: “It is deeply disappointing that the FDA has not exercised regulatory flexibility to meet patients’ needs, given the data supporting strong efficacy and the favourable safety profile.
“As we previously communicated, without timely accelerated approval, the development of RP1 will not be viable. We are devastated for our committed employees who have worked tirelessly for patients, but at this point, we have no choice but to eliminate jobs, including substantially scaling back our US-based manufacturing operations.”
Replimune previously offered a proposal with descriptive analysis from IGNYTE-3, supporting the components’ contributions. It also included data from IGNYTE that indicated a median progression-free survival of 30.6 months on RP1 with nivolumab, in contrast to 4.4 months on previous treatments.
The company sought feedback; however, the FDA did not provide a response and subsequently regarded the resubmission as a complete answer to the July 2025 CRL.
Issues were raised by the agency concerning tumour assessment techniques, with Replimune adhering to the FDA’s request to use RECIST 1.1 standards without alteration. The company submitted comprehensive analyses demonstrating consistent response rates, regardless of lesion treatment and confirmed that biopsies did not influence tumour response.
Before submitting the original BLA, Replimune engaged in regulatory discussions about trial design and patient criteria.
Although standard protocol calls for a randomised controlled trial, March 2021 Type B minutes revealed FDA suggestions that compelling data could justify consideration under an accelerated approval pathway.