FDA Grants Accelerated Approval to Replimune’s Tudriqev for PD-1–Resistant Advanced Melanoma

The U.S. Food and Drug Administration on Thursday granted accelerated approval to Tudriqev, a new treatment option for adults with unresectable advanced cutaneous melanoma whose disease has progressed after PD-1 immunotherapy. The drug, made by Replimune Inc., is approved for use in combination with nivolumab.

The decision addresses a hard-to-treat group of melanoma patients with limited options after standard PD-1-blocking regimens stop working. But the approval comes with an important caveat: It was granted under the FDA’s accelerated approval pathway, based on tumor response data rather than proof of longer survival or other direct clinical benefit, and continued approval will depend on post-approval trials confirming that benefit.

In its approval announcement, the FDA said the decision was supported by a single-arm, open-label, multiregional study of 140 adults with Stage IIIB, IIIC or IV unresectable advanced melanoma whose disease had progressed on anti-PD-1 therapy. In the FDA analysis cited in the approval, 91 patients were evaluable; 24% had an objective response, meaning their tumors shrank by a defined amount, and the median duration of response was about 14.1 months.

The path to approval was closely watched in part because FDA reviewers had publicly questioned how reliable and interpretable the trial’s efficacy results were before the decision. In briefing documents released ahead of a July 30 meeting of the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee, agency staff cited concerns including protocol changes, the limits of a single-arm trial with no comparison group, variation in patients’ prior treatment and disease burden, and the fact that some reported responders had only injected lesions or no non-injected target lesions, making it harder to judge whether benefit was systemic. Publicly reported efficacy figures also varied depending on the analysis: Replimune had reported a 33.6% objective response rate and 24.8-month median duration of response in the full 140-patient cohort, while FDA analyses produced lower estimates, including 15.7% in one intent-to-treat analysis and roughly 24% in a narrower evaluable set.

“For patients with advanced melanoma that has stopped responding to PD-1 blocking therapy, the prognosis is often devastating, and options have been far too limited. Clinicians managing these patients know this urgency firsthand,” Karim Mikhail, acting director of the FDA’s Center for Biologics Evaluation and Research, said in the agency’s announcement.

Tudriqev, or vusolimogene oderparepvec-wtpg, is a genetically modified herpes simplex virus type 1, or HSV-1, designed as an oncolytic immunotherapy — a treatment meant both to kill cancer cells and to stimulate an immune response against the tumor. The FDA said it is given by direct injection into tumors every two weeks for eight consecutive doses. The amount injected depends on tumor size, with a lower concentration used for the first dose and a higher concentration for later doses. Nivolumab is started intravenously at week 3.

The FDA said the most common side effects included fatigue, fever, infections, chills, musculoskeletal pain, nausea, diarrhea and injection-site reactions. The label also carries warnings about accidental spread of herpes infection to close contacts, herpes infection or reactivation in the patient, and complications related to the injections.

Tudriqev is not the first oncolytic viral therapy for melanoma. In 2015, the FDA approved Imlygic, another HSV-1-based therapy, for injectable unresectable melanoma lesions. What is new here is clearance for use with nivolumab in patients whose melanoma has already progressed after PD-1 treatment. The application had Breakthrough Therapy and Priority Review designations, and it follows a Complete Response Letter the company received in July 2025 before resubmitting the filing.