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July 17, 2025 - The U.S. FDA's Oncologic Drugs Advisory Committee (ODAC) has voted against two proposed combination regimens of GSK's antibody-drug conjugate (ADC) belantamab mafodotin (Blenrep®), with votes of 5-3 and 7-1 respectively rejecting:
Blenrep + bortezomib (Velcade®) + dexamethasone
Blenrep + pomalidomide (Pomalyst®) + dexamethasone
This decision sends several critical signals to the pharmaceutical industry:
Ocular Toxicity as Primary Barrier
The negative votes primarily reflected concerns over Blenrep's ocular toxicity profile, including corneal epitheliopathy, vision impairment, and corneal ulcers. In the DREAMM-7/8 trials, most patients experienced ocular adverse events versus. FDA reviewers concluded that the proposed toxicity management strategies failed to resolve these issues, creating a clinically problematic scenario where enhanced efficacy comes with disproportionately severe toxicity.
Insufficient U.S. Patient Data Raises Extrapolation Concerns
With U.S. patients constituting less than 5% of participants in both DREAMM-7 and DREAMM-8 trials, ODAC members challenged the validity of extrapolating these results to the American population. Several committee members explicitly stated that the lack of domestic data made proper risk-benefit assessment unfeasible, reflecting FDA's elevated standards for real-world representativeness in clinical evidence.
Dose Optimization Emerges as Critical Challenge
ODAC emphasized that GSK had inadequately explored optimal dosing strategies during extended development. The current regimens (2.5 mg/kg every 3 weeks or 1.9 mg/kg every 4 weeks) demonstrated suboptimal tolerability. The committee recommended GSK conduct further dose optimization studies to reduce toxicity while maintaining therapeutic efficacy.
Patient Perspective Contrasts with Regulatory Standards
The single supporting vote came from the patient representative, who stated that for relapsed/refractory multiple myeloma (RRMM) patients without curative options, Blenrep offers another potential treatment, with ocular toxicity being controllable through other means. However, the majority of committee members concluded that in the current competitive landscape - particularly with the emergence of BCMA-targeted CAR-T therapies and bispecific antibodies - the FDA is inclined to enforce more rigorous safety standards.
A Wake-Up Call for ADC Development
The Blenrep setback serves as a warning for BCMA-targeted ADC development, particularly for similar drugs advancing rapidly in China, highlighting the need to address therapeutic window, dose optimization, and patient representation early in development. The highly active payload's efficacy may come with dose-limiting toxicity, potentially limiting long-term clinical utility.
This ODAC decision underscores FDA's stringent requirements for safety, dose optimization, and domestic (U.S.) patient data, which may influence future drug review trends.
July 23, 2025 GSK disclosed that the FDA has postponed PDUFA date of the Blenrep® (belantamab mafodotin) combination therapy BLA. The agency established a new action date of October 23, 2025 for completion of BLA review.
Ref：
1，July 17, 2025: Meeting of the Oncologic Drugs Advisory Committee - 07/17/2025 | FDA
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July 23, 2025 GSK disclosed that the FDA has postponed PDUFA date of the Blenrep® (belantamab mafodotin) combination therapy BLA. The agency established a new action date of October 23, 2025 for completion of BLA review.
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