SHERIDAN, WYOMING – July 25, 2025 – The U.S. Food and Drug Administration (FDA) has cast doubt over GSK’s attempt to return its antibody-drug conjugate Blenrep to the U.S. market for relapsed or refractory multiple myeloma, citing persistent safety concerns and limited evidence of efficacy across key patient populations.
Once granted accelerated approval in August 2020, Blenrep was withdrawn in late 2022 after failing to demonstrate a progression-free survival (PFS) benefit in the DREAMM-3 confirmatory trial. Although GSK has since presented new clinical data from two subsequent Phase III studies—DREAMM-7 and DREAMM-8—the FDA has expressed skepticism about the drug’s overall benefit-risk profile.
Efficacy Gains Shadowed by Ocular Toxicity and Dosing Issues
In a briefing document released ahead of this week’s advisory committee (adcomm) meeting, FDA reviewers acknowledged that DREAMM-7 and DREAMM-8 met primary efficacy endpoints but pointed to serious concerns over tolerability. The agency stated, “The high rates of ocular toxicity and dose modifications, coupled with limited dose exploration, necessitate a careful evaluation of the risks associated with [Blenrep]. The benefit-risk profile of [Blenrep] for the proposed indications . . . remains unclear.”
The FDA also emphasized that Blenrep’s ocular toxicities are unlike those observed with other multiple myeloma treatments. “These ocular toxicities are ‘unique,’ noting that they are ‘not seen with any currently available treatments for multiple myeloma,’” the agency wrote.
Furthermore, the FDA questioned whether GSK had done enough to establish optimal dosing. “GSK appears to also have not ‘adequately optimized’ the dosing of Blenrep,” the reviewers wrote, referencing “high rates of ocular toxicity and poor tolerability” across both trials. They added, “On both trials, there were high rates of dose modifications.”
Questions Around Trial Diversity and Applicability
Another critical point raised by the FDA involved the demographic representation within GSK’s new studies. The agency noted, “In both trials, there was limited enrollment in the U.S., and limited enrollment of Black or African American patients and those 75 years of age and older,” adding that these shortcomings may “limit applicability” of the findings to the broader U.S. patient population.
These limitations pose a strategic obstacle for GSK as it seeks to relaunch Blenrep in a highly competitive and scrutinized therapeutic space. With multiple novel agents emerging in recent years for relapsed or refractory multiple myeloma, establishing both broad efficacy and a well-tolerated safety profile has become a non-negotiable benchmark for regulatory reentry.
Clinical Promise Met with Regulatory Caution
Despite the FDA’s reservations, GSK’s recent clinical readouts offer compelling data. DREAMM-7 showed that combining Blenrep with Takeda’s Velcade significantly improved PFS in relapsed or refractory patients, while additional data released in December indicated that Blenrep outperformed Johnson & Johnson’s Darzalex in the second-line setting. DREAMM-8 further reinforced the drug’s therapeutic potential, with Blenrep outperforming a Velcade-based regimen in terms of both PFS and treatment response.
Still, the FDA remains unconvinced. The agency is now turning to an external panel of oncology experts to determine whether GSK has identified a viable dosing strategy that balances efficacy with tolerability. This decision could determine whether Blenrep is granted reapproval in the U.S. or continues to remain off the market.
Corporate Context: Targeted Restructuring Underway
Adding to the high-stakes nature of the review, GSK confirmed this week that it would be laying off a “very limited” number of employees across its global operations. While no specifics were provided regarding scope or timeline, the news introduces additional complexity to the company’s current repositioning efforts.
As the industry awaits the outcome of Thursday’s adcomm, all eyes remain on whether Blenrep will be granted a second chance—or if FDA reservations will once again halt its return.
Learn more at www.gsk.com