SHERIDAN, WYOMING – July 21, 2025 – GlaxoSmithKline’s ambitions to relaunch its antibody-drug conjugate Blenrep for multiple myeloma treatment faced a critical blow last Thursday, as the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) rejected two proposed combination therapies over persistent safety and dosing concerns.
Safety Risks and Dosing Shortfalls Undermine Confidence
The advisory panel found that the benefits of Blenrep do not outweigh its risks for patients with relapsed or refractory multiple myeloma. In two separate votes, the committee expressed strong reservations about the drug’s risk-benefit profile:
- By a 7–1 margin, the panel voted against Blenrep combined with pomalidomide and dexamethasone.
- In a narrower 5–3 vote, the committee also rejected Blenrep in combination with bortezomib and dexamethasone.
“The efficacy data were strong but the toxicity data were also very strong,” said Neil Vasan, assistant professor at Columbia University Medical Center. “I really think this was just a missed opportunity over the course of many years of development of this drug to explore these different dosages.”
FDA Review Highlights Persistent Concerns
The FDA’s internal briefing documents echoed the panel’s conclusions, underscoring GSK’s failure to adequately optimize Blenrep’s dosing regimen. Key points raised included:
- High rates of ocular toxicity and poor tolerability.
- Frequent dose modifications in both Phase III studies used to support the application.
- Limited U.S. patient enrollment in both trials, particularly among Black or African American patients and individuals aged 75 and older.
“This is the United States FDA, so the proposed patient population [are] the United States patients. The clinical development program enrolled almost no patients in the United States,” emphasized Daniel Spratt of Case Western Reserve University. “It precludes any assessment of the benefit-risk profile in the U.S.”
Blenrep’s Rocky Regulatory Path
Originally approved under the FDA’s accelerated pathway in August 2020, Blenrep was withdrawn from the market in November 2022 following the failure of its confirmatory Phase III DREAMM-3 trial. GSK had since positioned itself for a comeback based on encouraging results from the DREAMM-7 and DREAMM-8 studies, both demonstrating improvements in progression-free survival.
In June 2024, GSK even forecasted that Blenrep could achieve “multi-blockbuster” status as a second-line treatment for multiple myeloma—a vision now under serious question following the ODAC decision.
Industry Implications and Strategic Outlook
The committee’s votes mark a significant setback for GSK’s oncology pipeline and highlight ongoing challenges in balancing efficacy with manageable toxicity in antibody-drug conjugates. The verdict also underscores the critical importance of robust U.S. trial participation for regulatory success.
While Blenrep’s future in the U.S. remains uncertain, the decision serves as a cautionary tale for pharmaceutical companies navigating the evolving oncology market, where regulatory expectations for safety, dosing optimization, and patient diversity are higher than ever.
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