The Food and Drug Administration on Thursday approved a Replimune treatment for advanced melanoma, ending a saga that saw the medicine rejected twice before physicians, patients and agency advisers persuaded the regulator to reconsider.
Formerly known as RP1 and to be sold as Tudriqev, the therapy was cleared for use alongside Bristol Myers Squibb’s Opdivo in people whose melanoma has progressed following treatment with immunotherapies like Opdivo or Merck & Co.’s Keytruda, which target a cancer-linked protein known as PD-1. An engineered oncolytic virus, Tudriqev is injected directly into tumors, where it reproduces and destroys diseased cells which then release immune-stimulating proteins.
The FDA granted Tudriqev an “accelerated” approval, meaning continued licensure is contingent on the success of an ongoing Phase 3 trial. That study is testing the Tudriqev-Opdivo combination against PD-1 drugs or chemotherapy, and is expected to produce results in late 2027.
Tudriqev’s clearance was based on the results of a single-arm trial in which the Tudriqev-Opdivo regimen helped around one quarter of enrollees achieve some level of tumor response. Those effects lasted a median of just over 14 months.
In briefing documents ahead of an advisory panel last week, FDA reviewers challenged those findings, arguing the way Replimune designed its trial and measured responses made distinguishing Tudriqev’s true impact difficult. A majority of experts convened by the agency disagreed, contending that the signal seen in testing was strong enough to support approval in a tough-to-treat patient population with few available treatments. Those panelists also noted that the pending confirmatory trial readout could provide more definitive answers quickly.
“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, the acting director of the FDA’s Center for Biologics Evaluation and Research.
The approval provides a much-needed lifeline for Replimune, which has warned that it might have to scrap development of Tudriqev if the therapy was turned back yet again. In a Monday note to clients, Leerink Partners analyst Daina Graybosch predicted the drug could achieve $618 million in peak annual sales if approved, while Wall Street’s consensus is closer to $1 billion.
Tudriqev has been swept up in the turmoil engulfing the FDA for much of the last year or so. Its first two rejections were issued under previous leadership, which was accused by several drugmakers of switching up regulatory guidance in spurning or delaying certain therapies. Replimune specifically charged the FDA with such a claim, arguing after Tudriqev’s last rejection in April that an earlier review team thought the company had provided “adequate evidence” to prove the treatment’s benefits.
Yet many trial investigators rallied to Replimune’s defense, and reportedly the White House intervened on its behalf. Following the advisory panel vote last week, Leerink analyst Graybosch expressed “high conviction” an approval would quickly follow, along with “strong demand” given the Tudriqev regimen’s “ease of access and benign safety profile.”
