NEW YORK — August 19, 2026 — Two weeks ago the FDA approved a treatment for advanced melanoma that works by injecting a genetically modified herpes virus directly into a patient's tumors. It is the first oncolytic viral therapy cleared for melanoma in eleven years, and it arrived only after the agency had rejected it twice.
Tudriqev — vusolimogene oderparepvec-wtpg, known through most of its development as RP1 — received accelerated approval on August 6 in combination with nivolumab. The indication is narrow and specific: adults with unresectable advanced cutaneous melanoma whose disease progressed on a PD-1-blocking regimen.
Dr. Dennis Porto, a double board-certified dermatologist and Mohs micrographic surgeon, says the indication is where the significance sits.
“Read that sentence carefully. Unresectable, and already failed immunotherapy. That is the group with almost nothing left. When people ask me whether a melanoma approval is a big deal, my first question is always which patients it is actually for, and this one is for the patients I have the least to offer.”
What an oncolytic virus does
The therapy is a herpes simplex virus type 1 that has been engineered in three ways. The genes that make HSV-1 neurovirulent have been removed. A fusogenic protein has been added, which causes infected cancer cells to fuse with their neighbors and die together. And the virus carries GM-CSF, an immune-signaling molecule that recruits immune cells to the site.
Injected into a tumor, it exploits a weakness cancer cells have already created for themselves. Tumor cells commonly disable their own antiviral defenses as they grow, which means a virus that healthy tissue would clear can replicate freely inside them until the cells rupture. That rupture is the mechanism, and it does two things at once: it destroys tumor directly, and it spills tumor antigens into an environment already flooded with immune-recruiting signal.
“It turns the tumor into its own vaccine. You are not manufacturing anything in a lab — the antigens are already there, sitting inside the lesion. The virus just opens it up in a way the immune system cannot ignore.”
That is also the argument for pairing it with nivolumab, a checkpoint inhibitor. The virus generates the immune response; the checkpoint inhibitor keeps it from being shut down. Treatment runs as eight intratumoral injections given every two weeks, dosed by tumor size, with imaging guidance for deeper lesions. Nivolumab is given intravenously alongside it.
The word doing the most work is “unresectable”
Dr. Porto is direct about how narrow this population is, and why that matters for how the news should be read.
“I spend my week removing skin cancers. Unresectable means someone has looked at the disease and concluded that surgery cannot get it — too many sites, too much spread, or a location where excision would cost more than it gains. That is not most melanoma. That is a small fraction, and it is the fraction where the outlook has been genuinely poor.”
The patients enrolled were sick. Roughly 80% had stage 4 disease, and all had progressed while on anti-PD-1 therapy, historically a point at which progression-free survival is measured in months rather than years.
“Nothing here changes what happens to a patient who walks in with a changing mole on their shoulder. That patient still gets an excision, and their odds are still excellent. This approval exists for the situation we all work very hard to keep people out of.”
What the numbers show — and what they don't
Approval was based on the IGNYTE trial: 140 patients enrolled, 91 in the efficacy-evaluable group. The objective response rate was 24.2%, with a median duration of response of 14.1 months.
Roughly one patient in four responded. Dr. Porto argues that both halves of that statistic deserve attention.
“A 24% response rate in a population that has already failed immunotherapy is meaningful. It is also three out of four patients who did not respond, and I think patients deserve to hear both numbers in the same breath. The durability is the part I find most encouraging — when it worked, it tended to keep working for over a year.”
The limitation the FDA repeatedly raised is structural. IGNYTE was single-arm, with no comparison group receiving nivolumab alone, so the contribution of the virus itself cannot be cleanly separated from the contribution of the checkpoint inhibitor. Reviewers also questioned whether a therapy injected into one lesion produces a genuine systemic effect — which is why the efficacy analysis was restricted to patients who had at least one tumor that was never injected.
This is an accelerated approval, granted on response rate rather than survival. A confirmatory phase 3 trial, IGNYTE-3, is running, and continued approval depends on it.
An approval that took three attempts
The regulatory history is unusual enough to be part of the story. The FDA issued a complete response letter in July 2025, and a second in April 2026, both times objecting that the trial design could not support the conclusion. Replimune resubmitted a third time without changing the trial — because the trial was finished.
In July, the agency's Cellular, Tissue, and Gene Therapies Advisory Committee voted 10 to 3 that the evidence was interpretable and clinically meaningful. Approval followed a week later.
“The data did not change. The interpretation did. I do not think that is scandalous — reasonable reviewers can weigh an imperfect dataset differently, especially when the alternative for these patients is nothing. But it is worth being honest that this was a judgment call about uncertainty, not a case where new evidence resolved the question.”
What patients and families should know
Practical points that tend to get lost in coverage. This is administered by injection into tumors, in a clinic, every two weeks for eight doses — a significant time commitment. Side effects reported were mostly mild to moderate: fatigue, fever, chills, injection-site reactions, and flu-like symptoms, which is roughly what one would expect from deliberately introducing a virus.
Because the therapy is a live herpes virus, there is a documented risk of herpes infection in the patient and of transmission to close contacts and to healthcare workers handling it. That is a real consideration for households, and one worth raising before treatment rather than after.
“If you or someone in your family is in this position, the question to ask an oncologist is not whether this is exciting. It is whether your particular pattern of disease has lesions that can be injected, and how it sequences against the trials you might otherwise be eligible for.”
Melanoma remains among the most consequential cancers dermatologists manage, with roughly 112,000 diagnoses and 8,510 deaths projected in the United States this year. Almost all of those deaths begin as a lesion that was, at some earlier point, small and entirely removable.
“Every advance at this end of the disease is worth having, and I am glad it exists. I would still rather see you three years earlier, when the whole treatment is a scar and a follow-up appointment.”
Dr. Dennis Porto, MD, MPH, FAAD is a double board-certified dermatologist and Mohs micrographic surgeon, and a Clinical Assistant Professor at Mount Sinai, where he teaches skin cancer surgery to dermatology resident physicians. He treats patients virtually through SkinCare.MD. A spot you are unsure about can be reviewed among the conditions his practice covers.
Journalists and researchers are welcome to quote from this article. Please attribute quotations to Dennis A. Porto, MD, MPH, FAAD, and cite www.skincare.md as the source. Dr. Porto is available for comment on dermatology and skin cancer topics; interview requests may be directed through the contact information at skincare.md.