Replimune announced on Aug. 6 that the United States Food and Drug Administration approved its cancer immunotherapy, now named Tudriqev, in combination with Bristol Myers Squibb’s Opdivo for adults with advanced melanoma who have experienced disease progression on an anti-PD-1 antibody-based regimen. The approval was granted under the FDA’s accelerated pathway based on objective response rate and duration of response.
Continued marketing approval of Tudriqev may be contingent on verification of clinical benefit in a confirmatory trial or trials, according to Replimune. “This is a transformative moment for Replimune, marking years of pioneering research to bring Tudriqev to patients desperately in need of new treatment options for advanced melanoma,” Replimune CEO Sushil Patel said in a prepared statement.
Karim Mikhail, acting director of the Center for Biologics Evaluation and Research at the FDA, said, “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. Today’s important milestone gives oncologists a meaningful new tool — and more patients a fighting chance.”
Tudriqev’s path to approval was uncertain following mixed feedback from last week’s Cellular, Tissue and Gene Therapies Advisory Committee meeting. The committee voted 10-3 in support of approval but raised concerns about trial design and data interpretation. Lawrence Schwartz, chair of radiology at Memorial Sloan Kettering Cancer Center who voted yes during the meeting, said, “This is messy data.” Patient representative Diane Aronson voted no and called the RECIST criteria used “confounding.” In briefing documents before the advisory meeting, FDA reviewers wrote that data from Replimune's registrational trial were "not interpretable," stating that "the response assessment used... confounds interpretation of the reported efficacy results and limits FDA's ability to verify the reported results."
In its Phase 1/2 IGNYTE study involving 140 patients with advanced melanoma whose disease progressed after anti-PD-1 therapy, Tudriqev plus Opdivo showed an objective response rate of 24.2% with a median duration of response at 14.1 months; adverse events were mostly mild-to-moderate according to Replimune.
Tudriqev had previously failed twice to secure FDA approval due to concerns over single-arm study results and trial design issues related to IGNYTE but ultimately received support from an advisory committee as part of renewed engagement by acting Commissioner Kyle Diamantas.
