The U.S. Food and Drug Administration has granted accelerated approval to Tudriqev (vusolimogene oderparepvec-wtpg), a genetically modified oncolytic viral therapy for adults with advanced melanoma that has stopped responding to anti-PD-1 immunotherapy.

According to a news release, Tudriqev, developed by Replimune, Inc., is approved in combination with nivolumab for adults with unresectable advanced cutaneous melanoma whose disease progressed while receiving a programmed death receptor-1 (PD-1)-blocking antibody-based regimen.

The approval offers a new treatment option for patients with anti-PD-1 refractory melanoma, an advanced form of skin cancer that no longer responds to a widely used class of immunotherapy drugs. Cancer can continue to grow despite treatment as it develops mechanisms that allow it to evade the immune system's ability to detect and destroy it.

The release said clinical trial data supporting the approval showed that 24% of evaluated patients achieved an objective response to Tudriqev, with responses lasting a median of 14.1 months. The FDA also considered input from clinical experts and patient advocates who highlighted the urgent need for effective treatments for patients with refractory disease.

“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,” said Karim Mikhail, B. Pharm., M.S., Acting Director of the Center for Biologics Evaluation and Research (CBER) in the release. “Today’s important milestone gives oncologists a meaningful new tool — and more patients a fighting chance.”

Tudriqev is an oncolytic viral therapy based on a genetically modified herpes simplex virus type 1 (HSV-1). The virus is engineered to selectively target and destroy cancer cells. After entering a tumor, it replicates and breaks cancer cells apart while also stimulating the body's immune system to recognize and attack the cancer.

When combined with nivolumab, an anti-PD-1 immunotherapy, Tudriqev may help restore an anti-tumor immune response in patients whose cancer previously stopped responding to immunotherapy.

The therapy is injected directly into tumors once every two weeks for eight consecutive doses. The amount administered is determined by the size of the tumor. The first dose uses a lower concentration, followed by a higher concentration for each remaining dose. Nivolumab is administered intravenously beginning at week three of treatment.

“For patients with advanced melanoma who have exhausted immunotherapy options, today’s approval offers a meaningful new path forward — grounded in early evidence and backed by the accountability that accelerated approval demands,” said Megha Kaushal, M.D., MSc., Acting Deputy Director of the CBER Office of Therapeutic Products.

The safety and effectiveness of Tudriqev were evaluated in an open-label, multiregional, single-arm clinical trial that enrolled 140 adults with Stage IIIB, IIIC or IV unresectable advanced melanoma. All participants had experienced disease progression after at least eight consecutive weeks of prior anti-PD-1-based therapy.

Of the 140 patients enrolled, 91 were evaluated for response. Among those patients, 24% achieved an objective response, with a median response duration of 14.1 months.

Per the release, the most common adverse reactions, reported in more than 10% of patients, were fatigue, fever (pyrexia), infections, chills, musculoskeletal pain, nausea, diarrhea, injection site reaction, headache, cough, influenza-like illness, rash, vomiting, itching (pruritus), arthralgia, constipation, decreased appetite, dizziness, dyspnea, hemorrhage, edema and abdominal pain.

Important safety warnings include the risk of accidentally spreading a herpes infection to close contacts, the possibility of a herpes infection developing or reactivating in the patient and complications related to the injection procedure.

The FDA convened its Cellular, Tissue, and Gene Therapies Advisory Committee on July 30 for a meeting on the Tudriqev application. The meeting included a public hearing in which patients, patient advocates, clinicians and independent experts provided input, followed by a session for committee members to discuss and deliberate the application.

Tudriqev received Breakthrough Therapy and Priority Review designations during the FDA review process.

The FDA's approval was granted under the accelerated approval pathway and is based on objective response rate and duration of response. As a condition of the accelerated approval, Replimune, Inc., must conduct post-approval trial(s) to verify and describe the clinical benefit of Tudriqev.

Continued approval may depend on verification of clinical benefit in confirmatory trial(s).