GlaxoSmithKline’s (GSK) effort to reintroduce its multiple myeloma antibody-drug conjugate Blenrep, to the U.S. market has encountered a significant hurdle. The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) voted against the approval of two Blenrep-based combination therapies.
GSK is seeking FDA approval for Blenrep in combination with Takeda’s Velcade (bortezomib) and dexamethasone, as well as with Bristol Myers Squibb’s Pomalyst (pomalidomide) and dexamethasone. These combinations are intended for patients with multiple myeloma who have received at least one prior line of therapy.7
The committee reviewed data from GSK’s DREAMM-7 and DREAMM-8 phase 3 trials. In briefing documents released ahead of the meeting, the FDA pointed to “high rates of ocular toxicity” in both studies. Most participants experienced keratopathy and visual acuity events, while some cases involved more serious conditions such as corneal ulcers. The agency also noted “high rates of dose modifications,” raising concerns about whether the evaluated doses were “adequately optimized.”
ODAC members were tasked with evaluating whether the overall benefit-risk profile of Blenrep in each proposed combination was favorable “at the proposed dosage in the proposed patient population.” The vote resulted in a 5-3 outcome against the Velcade combination and a 7-1 vote against the Pomalyst pairing.
Concerns during the meeting focused on toxicity, dose optimization, and trial demographics. Less than 5% of patients enrolled in either of the pivotal trials were from the United States. Several panel members emphasized that this limited enrollment impeded their ability to assess the benefit-risk profile for U.S. patients. One panelist remarked that the study “precludes any assessment of the benefit/risk profile in the U.S.” due to the lack of U.S.-based participants.
Neil Vasan, assistant professor at Columbia University Medical Center, voted against both combinations. He stated, “The efficacy data were strong but the toxicity data were also very strong,” and added that insufficient dose exploration during the drug’s development process was a missed opportunity.7
Other members of the committee cited dosage concerns as central to their decisions, with one noting that additional work was needed to determine an “optimal dose” that ensures both safety and efficacy. For some panelists, the limited demographic representation was a key issue. The FDA had previously stated that the minimal enrollment of older patients and those identifying as Black or African American may “limit applicability” to the U.S. population.
The only vote in favor of both combinations came from John DeFlice, M.D., a patient representative on the panel. He stated, “Based on the clinical experience of the researchers and the testimonies that we’ve heard, this is an amazing drug for an incurable disease.” DeFlice also expressed that the questions posed to the committee were not the right issues to evaluate.
Public speakers during the meeting supported Blenrep, emphasizing patient need and describing the ocular side effects as generally manageable.
Blenrep was initially granted accelerated FDA approval in 2020 as a fifth-line monotherapy treatment for multiple myeloma but was voluntarily withdrawn from global markets in 2022 after it did not meet endpoints in a confirmatory study. Despite this, GSK projected peak sales of more than 3 billion pounds sterling for the drug in its proposed combinations, which have already been approved in the U.K. and Europe.
