FDA Calls Replimune RP1 Melanoma Data 'Not Interpretable,' Shares Plunge 32%

The FDA’s review staff concluded that the single-arm IGNYTE study supporting Replimune’s (REPL) RP1 plus nivolumab in advanced melanoma is “not interpretable,” according to briefing documents published July 28, 2026. The documents were released two days ahead of a July 30 meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC).

REPL shares fell more than 32% to $5.78 in intraday trading on July 28, according to BioSpace. The stock had closed at $8.63 on July 25, the prior trading day. The crash wiped out roughly $300 million in market capitalization for the clinical-stage oncolytic virus company, which has no approved products and no revenue.

Update July 31, 2026 (Polygon): The crash was fully reversed after the CTGTAC advisory committee voted 10-3 on July 30 that RP1 plus nivolumab has a favorable benefit-risk profile, despite the FDA staff’s briefing-docs concerns. REPL surged from $5.41 (July 29 close) to $11.20 (July 31 close, Polygon), a 107% rebound. Cantor Fitzgerald upgraded the stock to Overweight with a $12 price target. The August 2 PDUFA date falls on a Sunday; the FDA may act July 31 or August 3. See our full AdComm vote coverage.

What the FDA said

The FDA released briefing documents ahead of the Thursday CTGTAC meeting to review the biologics license application for vusolimogene oderparepvec (RP1) in combination with Bristol Myers Squibb’s Opdivo (nivolumab) for adults with unresectable advanced cutaneous melanoma who progressed after anti-PD-1 therapy.

Agency reviewers wrote that the response assessment used in the Phase 1/2 IGNYTE study “confounds interpretation of the reported efficacy results and limits FDA’s ability to verify the reported results.” The FDA also determined that the objective response data from the single-arm trial “are not of sufficient magnitude to overcome concerns” about efficacy, and that without a reliable historical control “it cannot be determined whether RP1 contributes to any observed effect” when combined with nivolumab.

“The overall survival analysis from the single-arm IGNYTE study is not interpretable,” the FDA wrote.

The briefing documents “read negatively” for Replimune’s shares, BMO Capital Markets said in a Tuesday note. BMO added that the AdComm panel “skews negatively for the vote.”

Replimune’s response

Replimune argued in its own briefing document that a randomized trial is unethical in this population, since there were no treatments available for patients who had progressed on anti-PD-1 therapy when IGNYTE was conducted. The company also noted that the FDA has previously granted melanoma approvals based on single-arm studies, citing Iovance’s Amtagvi (2024), Merck’s Keytruda, and BMS’s Opdivo and Yervoy.

Third submission, same objection

RP1 has been rejected by the FDA twice. The first Complete Response Letter in July 2025 said the agency “did not consider IGNYTE an adequate and well-controlled clinical investigation.” A second CRL in April 2026 maintained the same objection, with the FDA writing it “would not recommend” seeking approval based on a single-arm study.

The June 2026 resubmission was classified as a Class 1 response, the most expedited review type. The FDA set a PDUFA date of August 2, 2026, and scheduled the July 30 AdComm. The CTGTAC will vote on a single question: Are the efficacy results from IGNYTE evaluable and clinically meaningful?

What to watch next

The July 30 AdComm vote. BMO described Replimune as “down to final at-bat,” noting that clinicians on the panel could still push for approval based on the long-term OS data, “even if influenced by heterogeneity.” The AdComm vote is advisory; the FDA’s final decision is due by August 2. A negative vote makes a third CRL likely. A positive or split vote could preserve a narrow path given the lack of options for post-anti-PD-1 melanoma patients.

Update July 30, 2026: The CTGTAC voted 10-3 in favor of RP1, rejecting the FDA’s own briefing-docs stance. REPL surged 39% in after-hours trading. See our full AdComm vote coverage.

This is the second AdComm briefing documents event this week. On July 27, the FDA released documents disputing Capricor’s HOPE-3 Phase 3 results for deramiocel in Duchenne muscular dystrophy, sending CAPR down 65% ahead of a July 29 vote. The back-to-back briefing docs releases mark the end of a nine-month AdComm drought at the FDA under the Trump administration.

BioSpace coverage | FDA briefing documents (PDF) | FDA AdComm meeting announcement | AdComm vote result | Replimune RP1 PDUFA preview