Vusolimogene oderparepvec-wtpg

iStock, sasha85ru Replimune’s immunotherapy for advanced melanoma faced a perilous regulatory road with two previous rejections, but the drug—to be marketed as Tudriqev—prevailed with strong support from oncologists and a 10-3 advisory committee vote in its favor. Replimune has prevailed at long last. ON Thursday, the FDA approved the biotech’s cancer immunotherapy in combination with Bristol Myers Squibb’s Opdivo for advanced melanoma—putting a bow on a long-running regulatory saga. The drug with a storied history and many names: vusolimogene oderparepvec-wtpg, RP1, and now to be marketed as Tudriqev, won the FDA’s accelerated nod, 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 based on objective response rate and duration of response, according to Replimune’s announcement late Thursday afternoon. Continued marketing approval of Tudriqev “may be contingent on verification of clinical benefit in a confirmatory trial(s),” Replimune said. ezstandalone.cmd.push(function () { ezstandalone.showAds(129); }); “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 on Thursday. The FDA in its statement similarly focused on the high unmet need in advanced melanoma. “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, acting director of the Center for Biologics Evaluation and Research, in a prepared statement. “Today’s important milestone gives oncologists a meaningful new tool — and more patients a fighting chance.” Shares of Replimune were up nearly 9% to $12.86 when the market closed on Thursday. An approval for Tudriqev was anything but certain. Last week, the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC), voted 10-3 in support of the drug. The FDA is not obligated to follow the advice of advisory committees, though often does. FDA Replimune overcomes ‘messy data’ to secure positive adcomm vote for melanoma therapy The FDA’s Cellular, Tissue and Gene Therapies advisory committee voted 10 to 3 in favor of Replimune’s immunotherapy for advanced melanoma in combination with Bristol Myers Squibb’s Opdivo, but trial design was a major sticking point as the panel deliberated. July 30, 2026 · 5 min read · Michael Gibney Read more The advisors’ feedback was mixed, however—leaving the question of approval in doubt. “This is messy data,” said Lawrence Schwartz, chair of the department of radiology at Memorial Sloan Kettering Cancer Center, who ultimately voted “yes,” during the meeting. Several members of the committee said RP1 showed important efficacy signals but that criteria needed to be better established for decisions based on response evaluation criteria in solid tumors (RECIST) down the road. Patient Representative Diane Aronson was one of those thrown by the data. Aronson, who voted no, called the RECIST criteria “confounding.” RECIST was a primary concern for the FDA as well. In briefing documents released days before the adcomm, FDA reviewers said data from Replimune’s registrational trial were “not interpretable.” 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 reviewers added, laying out the agency’s seemingly definitive position. In the IGNYTE trial, which comprised 140 patients, Tudriqev plus Opdivo elicited an objective response rate of 24.2%, with a median duration of response of 14.1 months. Tudriqev was “well tolerated with mostly mild-to-moderate adverse events,” according to Replimune. The adcomm was scheduled so close to Replimune’s original FDA decision date of August 2, it raised the question of whether the agency would follow what appeared to be a predetermined position regardless of the committee’s vote. Editorial Chaotic adcomms threaten to derail FDA’s bid to renew trust after Makary, Prasad The FDA has been trying to mend fences with rare disease drug developers and patient groups since the departure of former Commissioner Marty Makary three months ago. But advisory committee meetings last week for Replimune and Capricor Therapeutics only created more confusion and frustration. August 5, 2026 · 6 min read · Heather McKenzie Read more Tudriqev has faced a challenging regulatory road. The engineered viral immunotherapeutic was first rebuffed by the FDA in July 2025 , with reviewers writing in the CRL that they “would not recommend” seeking approval based on results from a single-arm study. The drug again failed to secure approval in April , with the FDA taking issue with the design of Replimune’s IGNYTE study. Replimune’s adcomm on July 30 was part of a return to advisory committee meetings reportedly spearheaded by acting FDA Commissioner Kyle Diamantas after a 9-month drought . Moderna won approval on Wednesday for the mRNA-based flu vaccine mFLUVISA after an adcomm gave the shot its unanimous backing in June. Capricor Therapeutics also endured an adcomm the day before Replimune’s for its cell therapy for Duchenne muscular dystrophy cardiomyopathy. Capricor did not fare as well, with advisors voting 9-3 against approval of deramiocel. Capricor is awaiting a decision on or before August 22. The two adcomms were largely viewed in the biopharma industry as a bellwether, both for how the FDA would interact with its advisory committees, and for the rare disease space, which has recently enjoyed greater regulatory flexibility.

iStock, wildpixel The FDA has been trying to mend fences with rare disease drug developers and patient groups since the departure of former Commissioner Marty Makary three months ago. But advisory committee meetings last week for Replimune and Capricor Therapeutics only created more confusion and frustration. The FDA has taken great strides since the end of the Makary administration to rebuild trust with industry—and the rare disease space, in particular. Two advisory committee meetings last week may have blown all that goodwill out of the window. “There were some really disingenuous things that were done to put together the analysis that they came up with,” Mindy Leffler said of the FDA’s arguments to the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) last Wednesday regarding Capricor Therapeutics’ Duchenne muscular dystrophy (DMD) cardiomyopathy cell therapy. The consultant and mother of a patient in the Phase 2 trial for deramiocel appeared shell-shocked by the adcomm when she spoke with me from a hotel lobby after testifying the previous day. The committee voted 9-3 against recommending the therapy’s approval. Leffler said her son Aidan’s left ventricular ejection fraction (LVEF) had fallen by 5% prior to treatment with the cell therapy in deramiocel’s Phase 2 trial. Five years later, his cardiac function is stable, she said. If deramiocel is not approved, Aidan will lose access to it. ezstandalone.cmd.push(function () { ezstandalone.showAds(129); }); Capricor CEO Linda Marbán was similarly stunned by how the adcomm unfolded. She told me that she would not rule out legal action over the statistical analysis of the company’s Phase 3 HOPE-3 trial. Replimune’s adcomm meeting, held the following day, delivered a more positive outcome for the company, with the CTGTAC voting 10-3 in favor of approving RP1 for advanced melanoma. But the FDA’s presentation was consistent with its previously released briefing documents , in which reviewers argued Replimune’s registrational trial was “not interpretable.” Now, the decision date for the drug has come and gone without word from the FDA. Replimune, the medical community—which has voiced its strong support for RP1—and patients are now back in an indeterminate limbo. This is exactly the type of PR nightmare the FDA had been trying to rise over since former Commissioner Marty Makary left in the middle of May. Under his leadership, alongside former Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad, rare disease drug developers endured a regulatory rollercoaster the past 18 months—one they didn’t realize they’d bought a ticket to ride. Previous FDA guidance was reversed and therapies including deramiocel and RP1 were unexpectedly rejected, throwing programs—and stock prices—into turmoil. Soon after Makary and Prasad departed the agency this spring, Acting Commissioner Kyle Diamantas met with rare disease groups seeking to “repair relations with a sector disappointed by his predecessor,” according to Reuters . Indeed, the clouds appeared to be clearing for the rare disease space, as the FDA’s temporary leaders reversed recent decisions made under Makary and Prasad. In June, the agency agreed that three-year data from the Phase 1/2 trial of uniQure’s Huntington’s disease gene therapy could support an accelerated approval application and that a sham surgery–controlled Phase 3 study may not be necessary. This directly contradicted guidance given by CBER in November 2025 and cleared the way for a biologics license application submission this quarter. Next aboard the regulatory reversal train was REGENXBIO , which plans to resubmit its Hunter syndrome gene therapy— rejected in February—in Q3 for approval after the new FDA leadership deemed existing clinical data sufficient for consideration for accelerated approval. Just a few days later, the FDA accepted Replimune’s resubmission and assigned an August 2 action date for the twice rebuffed RP1. When the regulator then scheduled advisory committee meetings for RP1 and deramiocel—whose resubmission was accepted by the FDA in March under Makary and Prasad—many assumed it was part of Diamantas’ bid to restore transparency at the agency after what Capital Alpha in May declared the “most damaging period in FDA history.” But attending both CTGTAC meetings last week, I wondered: Was it all for show? At the very least, it’s not a good look letting Replimune’s action date pass by without a mention. Now, it’s a waiting game. FDA Replimune overcomes ‘messy data’ to secure positive adcomm vote for melanoma therapy The FDA’s Cellular, Tissue and Gene Therapies advisory committee voted 10 to 3 in favor of Replimune’s immunotherapy for advanced melanoma in combination with Bristol Myers Squibb’s Opdivo, but trial design was a major sticking point as the panel deliberated. July 30, 2026 · 5 min read · Michael Gibney Read more All for show? Replimune’s adcomm was scheduled for just three days before the PDUFA date—giving the FDA precious little time to consider the advisors’ feedback. What’s more, per internal FDA and CBER standard practice, when a PDUFA date falls on the weekend—August 2 was Sunday—the actual target action date becomes the preceding Friday, according to Don Fink , cell and gene therapy master practice expert and former FDA expert biologist. That means the agency was supposed to render a decision the day after the adcomm and is currently four days late. Does Replimune have a chance, or was the FDA simply going through the motions with the adcomm? “My take is FDA went to great lengths in their briefing document and presentation to support what I judge to be their already determined position at the time of the advisory committee (AC) meeting that the clinical results are insufficient to support an accelerated approval and will issue a third Complete Response Letter (CRL),” Fink said in a LinkedIn post on Friday. Indeed, Sundeep Agrawal, associate director of clinical programs at the FDA’s oncology center of excellence, was blunt when he described the agency’s position. “Contribution of effect and the need for each product has not been demonstrated, and the applicants that submitted overall survival or [overall survival] data and analysis is not interpretable,” he told the CTGTAC. Specifically, the FDA says it cannot determine how much of the effect could be attributed to RP1 versus the approved drug with which it was paired, BMS’ Opdivo. But Replimune seems to have an ace in its pocket—the very public support of several cancer specialists. Last August—after RP1’s initial rejection in July—22 scientists who designed the drug’s Phase 3 IGNYTE trial wrote an open letter to the FDA petitioning for re-review. So it was reasonably foreseeable that the temporary voting members on the adcomm’s roster—many oncology and melanoma experts—would come down on the side of their peers and recommend RP1’s approval. Despite some misgivings—one panelist who voted yes called the data “messy”—the FDA’s advisors voted largely in concert with their petition-penning peers. The FDA is not obligated to follow the advice of its advisory committees, but typically does not counter an adcomm’s vote. And it certainly would raise eyebrows just as interim leadership has begun to gain traction with a frustrated industry and patient groups. Has FDA now backed itself into a corner with a drug it never wanted to approve? For Capricor as well, the FDA appeared to have already stacked the cards against deramiocel. “It was very clear from the voting question and sort of how [FDA] pitched it with stat plan 1.1 that they seem to have some type of ulterior motive in trying to take this therapeutic down, and I can’t figure out why,” Marbán told me after last Wednesday’s adcomm. As for transparency, Capricor was unaware that the FDA had any issues with its data as late as the end of June. “We really thought that it’s a very clean data set,” Marbán told me in June after the adcomm was scheduled. “We have not gotten any issues that they want to discuss.” The non-communication wasn’t for lack of trying on Capricor’s part. Marbán said last week that the biotech had requested a meeting with the FDA weeks before the adcomm took place. Here, a lack of transparency led to an adcomm where the two parties were misaligned on which statistical analysis plan to review, the endpoints that should have been studied, and even the target indication, which did not align with the Phase 3 trial’s primary endpoint. This is not a good look for the FDA, particularly as it tries to right the ship after months of mayhem. Now talk of legal action is flying around after the Capricor adcomm—both from and at the biotech —and Replimune is stuck in limbo. It seems that turbulent waters still persist at the FDA. Regulatory Capricor CEO won’t rule out legal action against FDA after negative adcomm After an FDA advisory committee voted 9-3 on Wednesday against recommending Capricor Therapeutics’ Duchenne muscular dystrophy cardiomyopathy drug for approval, stakeholders allege an “ulterior motive” and “biased intentions.” July 31, 2026 · 6 min read · Heather McKenzie Read more