The U.S. Food and Drug Administration has granted accelerated approval to Tudriqev (vusolimogene oderparepvec-wtpg), an engineered herpes virus that seeks out and destroys cancer cells, clearing it in combination with nivolumab for adults with advanced cutaneous melanoma whose disease progressed on anti-PD-1 immunotherapy.
Tudriqev is a first in at least two ways. It is the first genetically modified oncolytic viral therapy approved specifically for patients whose melanoma no longer responds to checkpoint inhibitors, and it is the first to pair a modified herpes simplex virus type 1 with an anti-PD-1 agent in a bid to restart an anti-tumor immune response in a patient population that has very few remaining options.
Anti-PD-1 refractory melanoma is advanced skin cancer that continues to grow despite treatment with checkpoint inhibitors, a widely used class of immunotherapy drugs, because the tumor has developed ways to evade the immune system’s surveillance. Roughly one in four patients in the pivotal trial responded to Tudriqev combined with nivolumab, and those responses lasted a median of nearly 14 months, according to the FDA.
“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,” said Karim Mikhail, B. Pharm., M.S., Acting Director of the Center for Biologics Evaluation and Research (CBER). “Today’s important milestone gives oncologists a meaningful new tool, and more patients a fighting chance.”
Tudriqev is based on a herpes simplex virus type 1 that has been genetically modified to selectively target and destroy cancer cells. Injected directly into tumors once every two weeks for eight consecutive doses, the virus replicates inside tumor cells, lyses them, and in doing so alerts the patient’s immune system to the cancer’s presence. When paired with nivolumab, an anti-PD-1 immunotherapy that had previously stopped working on its own, the combination may restore an immune attack against the tumor. A lower viral dose is used for the first injection, followed by a higher concentration for the remaining seven. Nivolumab is administered intravenously starting at week three.
The approval rests on an open-label, single-arm, multiregional trial enrolling 140 adults with unresectable Stage IIIB, IIIC, or IV melanoma that progressed after at least eight weeks of prior anti-PD-1-based therapy. Among 91 patients evaluated for efficacy, 24 percent achieved an objective response, with a median response duration of 14.1 months.
The most frequently reported side effects, occurring in more than 10 percent of patients, included fatigue, fever, infection, chills, musculoskeletal pain, nausea, diarrhea, injection site reactions, headache, cough, influenza-like illness, rash, vomiting, itching, joint pain, constipation, decreased appetite, dizziness, shortness of breath, bleeding, edema, and abdominal pain. The FDA flagged three important safety risks: the possibility of inadvertently spreading herpes to close contacts, herpes infection or reactivation in the patient, and complications related to the injection procedure itself.
The application was reviewed under the FDA’s accelerated approval pathway, which allows earlier approval based on surrogate endpoints such as objective response rate, provided the sponsor conducts post-approval confirmatory trials to verify clinical benefit. Continued marketing approval may depend on those results. The agency also convened an advisory committee meeting on July 30, which included a public hearing with patients, advocates, clinicians, and independent experts, and granted both Breakthrough Therapy designation and Priority Review. The approval went to Replimune, Inc.
Source: FDA Press Announcement
