The Food and Drug Administration granted accelerated approval on August 6 to Tudriqev, an injected virus-based immunotherapy, in combination with nivolumab for adults whose unresectable advanced cutaneous melanoma has progressed on a PD-1 blocking antibody-based regimen. The decision reverses two prior rejections and gives patients in one of oncology's most difficult positions a new option while a confirmatory trial runs.
The population this reaches is specific and currently underserved. About half of melanoma patients do not respond to checkpoint blockade or progress after it, and more than half of patients treated with checkpoint inhibitors progress within six months. Median overall survival after that progression is under one year.
For a family sitting in an oncology consultation next week, the practical change is that a therapy previously available only through a clinical trial can now be prescribed. The equally practical caveat is that accelerated approval here rests on tumor response rather than proven survival benefit, and that distinction should shape expectations.
A Regulatory Path That Took Three Attempts
The approval closes a review history unusual in its length. The FDA issued a complete response letter in July 2025, stating that the supporting IGNYTE trial was not an adequate and well-controlled investigation and could not be reliably interpreted because of heterogeneity in the patient population.
A second complete response letter followed on April 10, 2026. As Targeted Oncology described the second rejection, the agency said it could not isolate the contribution of the oncolytic therapy from that of nivolumab in a single-arm trial without a contemporaneous control, and noted that many responders had all target lesions injected, which limited what the data could show about systemic activity.
Replimune resubmitted a third time, and the agency accepted the filing with a goal date of August 2. The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee voted 10 to 3 on July 30 in the company's favor, and the agency's oncology approval notice records that the meeting included a public hearing with patients, advocates, clinicians, and independent experts. The decision arrived four days after the target action date, which fell on a Sunday. MedicalDaily previously reported on the advisory committee vote preceding this decision.
Inside the Trial That Supported the Decision
The label rests on IGNYTE, an open-label, multicenter Phase 1/2 study. Its registrational melanoma cohort enrolled 140 patients with confirmed progression after at least eight weeks of anti-PD-1-based therapy, with or without anti-CTLA-4. Of those, 91 patients with at least one non-injected lesion formed the efficacy-evaluable population.
In that group, the combination produced an objective response rate of 24.2 percent with a median duration of response of 14.1 months, according to Replimune's announcement. The IGNYTE data have been published in the Journal of Clinical Oncology.
The evidence has real limits. IGNYTE was a single-arm study without a randomized comparison group, which is the interpretability problem FDA reviewers raised repeatedly. Response rate and duration are the basis for accelerated approval, and continued approval may depend on verification of clinical benefit in the ongoing Phase 3 IGNYTE-3 trial, which randomizes roughly 400 patients against the physician's choice of therapy with overall survival as the primary endpoint. That trial's estimated primary completion date is in 2029.
Michael K. Wong, the IGNYTE primary investigator and a former physician in chief and professor of oncology at Roswell Park Comprehensive Cancer Center, said in the company release that "advanced melanoma patients have few options after anti-PD-1 therapy and face high morbidity and poor survival outcomes." Wong served as principal investigator on the Replimune-sponsored trial, and his comments appear in company materials.
Patients Most Likely to Be Eligible
The indication covers adults with unresectable advanced cutaneous melanoma who progressed on a PD-1 blocking antibody-based regimen. In the trial population, 80 percent had Stage 4 disease, 13 percent had received prior adjuvant anti-PD-1 treatment, 54 percent were PD-L1 negative, 45 percent had lung lesions, and 24 percent had liver lesions, which is why the company describes the label as broad within that setting.
Administration is not a simple infusion. The therapy is injected directly into tumors, including deep and visceral lesions, with imaging guidance for internal sites, and dosing is based on tumor size. That requires a center equipped for image-guided injection.
Safety deserves attention alongside efficacy. Serious adverse reactions occurred in 35 percent of the 140 treated patients, and 2.9 percent discontinued permanently. Common reactions included fatigue, fever, chills, nausea, diarrhea or colitis, injection site reactions, and musculoskeletal pain. Because the product is a modified herpes simplex virus, the label warns healthcare providers, caregivers, close contacts, pregnant women, and newborns to avoid direct contact with injected tumors, dressings, or patients' bodily fluids. The label also flags herpetic infection or reactivation and visceral injury as warnings.
Cost, Access, and the Evidence Still Owed
Replimune has not published a list price, and coverage decisions from commercial insurers, Medicare, and Medicaid will follow their own timelines. The company says eligible patients prescribed the therapy will have access to a support program covering access, reimbursement, and financial assistance. Patients facing a denial can ask their oncology team about prior authorization documentation and appeals.
Availability will also depend on which centers can deliver image-guided intratumoral injection. Patients in metropolitan areas with academic cancer centers are likely to see access first. Those in rural regions may need referral, and travel costs are a real barrier that oncology social workers can sometimes help address.
Nobody should read this approval as a cure claim. A response rate near one in four means most patients in the trial did not respond, a point the FDA's announcement of the approval reflects in describing the benefit as a new tool rather than a breakthrough cure. What the approval provides is an additional option in a setting where options are scarce, with the survival question still open.
Until IGNYTE-3 reports, decisions about whether this therapy fits a particular patient belong to a treating oncologist who knows the disease burden, prior treatments, and lesion locations involved.
Key Questions Answered
What did the FDA approve? Accelerated approval for Tudriqev, also known as vusolimogene oderparepvec-wtpg, in combination with nivolumab for adults with unresectable advanced cutaneous melanoma that progressed on a PD-1 blocking antibody-based regimen.
Why was it rejected twice before? The FDA issued complete response letters in July 2025 and April 2026, saying the supporting trial was not adequate and well-controlled and that its results could not be reliably interpreted because of the mixed patient population.
What does accelerated approval mean here? The approval is based on objective response rate and duration of response rather than proven survival benefit. Continued approval may depend on verification of clinical benefit in a confirmatory trial.
How well did it work in the trial? Among 91 evaluable patients, 24.2 percent had an objective response, with a median duration of 14.1 months. Most patients in the trial did not respond.
How is it given? By direct injection into tumors, including deep and visceral lesions, using imaging guidance for internal sites. Dosing is based on tumor size.
What are the main safety concerns? Serious adverse reactions occurred in 35 percent of treated patients. Because the therapy is a modified herpes virus, caregivers and close contacts are advised to avoid contact with injected tumors, dressings, and bodily fluids.
Who should patients talk to about eligibility? A treating oncologist. Eligibility depends on prior therapy, disease extent, and whether lesions can be safely injected.
