Troubles mount for GSK's Blenrep in multiple myeloma treatment as the FDA raises concerns about its comeback
GlaxoSmithKline (GSK)'s antibody-drug conjugate (ADC) Blenrep (belantamab mafodotin) is undergoing renewed regulatory scrutiny in the United States for the treatment of relapsed or refractory multiple myeloma (RRMM), specifically in combination with other agents.
The U.S. Food and Drug Administration (FDA) is currently reviewing GSK’s Biologics License Application (BLA) for Blenrep in two triplet combinations: with Takeda’s Velcade (bortezomib) and dexamethasone (BVd), and with Bristol Myers Squibb’s Pomalyst (pomalidomide) and dexamethasone (BPd), for adults with RRMM who have received at least one prior line of therapy. The Oncologic Drugs Advisory Committee (ODAC) is meeting on July 17, 2025, to discuss the benefit-risk profile, appropriate dosing, and the extent of ocular toxicity.
The FDA's primary concern is a high rate of ocular toxicity, including corneal disease (keratopathy) and changes in visual acuity, which were flagged in FDA briefing documents. These side effects have previously led to the U.S. withdrawal of Blenrep in 2022 after confirmatory trial shortcomings. The FDA has raised concerns about ocular toxicities in patients treated with Blenrep, which are not seen with any currently available treatments for multiple myeloma.
GSK's Phase 3 DREAMM-7 and DREAMM-8 trials have shown that Blenrep-based combinations improved progression-free survival (PFS), and in the case of DREAMM-7, also overall survival (OS), compared to standard-of-care regimens. The FDA believes that GSK has not adequately optimized the dosing of Blenrep, as shown by the high rates of ocular toxicity and poor tolerability in the DREAMM-7 and DREAMM-8 trials.
The ODAC is tasked with evaluating whether the demonstrated efficacy outweighs these safety risks, particularly given the availability of other treatments for RRMM. If the FDA approves Blenrep, it would mark a significant comeback for the drug in the U.S. ADC market. GSK has projected substantial peak sales for Blenrep, contributing to an upward revision of its long-term financial targets.
The FDA's approval for Blenrep was withdrawn in February 2023. Blenrep was pulled from the U.S. market in November 2022 after a confirmatory trial failed to significantly improve progression-free survival (PFS). However, additional data from the DREAMM-7 trial announced in December showed that Blenrep outperforms Johnson & Johnson's Darzalex in the second-line setting. GSK also presented data from DREAMM-8 last year, announcing in a June presentation that Blenrep bests a Velcade-based regimen in terms of PFS and treatment response.
The limited enrollment of Black or African American patients and those 75 years of age and older in the DREAMM-7 and DREAMM-8 trials may "limit applicability" of their findings to U.S. patients, according to the agency’s briefing document Tuesday.
In conclusion, Blenrep’s potential U.S. reintroduction hinges on the FDA’s assessment of its benefit-risk profile, particularly in light of persistent ocular safety concerns and dosing uncertainties. While recent clinical data support its efficacy in RRMM, the FDA’s upcoming decisions will determine whether Blenrep can re-enter the U.S. market and under what conditions.
- Despite the demonstrated efficacy of GSK's Blenrep in the treatment of relapsed or refractory multiple myeloma, the U.S. Food and Drug Administration (FDA) is carefully evaluating the drug due to concerns about chronic ocular toxicities and optimized dosing.
- The FDA's concern regarding Blenrep's high rates of ocular toxicity, such as keratopathy and changes in visual acuity, stems from data showing these side effects are not seen with other treatments for multiple myeloma.
- The approval of Blenrep could have significant implications for both science and health-and-wellness, as it could mean a comeback for this medication in the United States and contribute to substantial sales for GSK, impacting their long-term financial targets. However, the FDA's ongoing deliberations about Blenrep's benefit-risk profile and appropriate therapies-and-treatments for medical-conditions like multiple myeloma are crucial in determining its future in the market.
