GSK's Blenrep Faces Setback as FDA Advisory Committee Votes Against Approval

GSK's antibody-drug conjugate Blenrep has encountered a significant obstacle in its bid to return to the market for multiple myeloma treatment. The U.S. Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) voted against recommending approval for two proposed combination regimens, citing safety concerns and inadequate dosing optimization.

Advisory Committee's Decision

The ODAC convened on Thursday to evaluate two Blenrep combination therapies for patients with relapsed or refractory multiple myeloma. In a 7-1 vote, the panel determined that the benefits of Blenrep plus pomalidomide and dexamethasone did not outweigh the risks. Similarly, the committee voted 5-3 against the combination of Blenrep with bortezomib and dexamethasone.

Dr. Neil Vasan, assistant professor at Columbia University Medical Center, explained his negative votes, stating, "The efficacy data were strong but the toxicity data were also very strong. 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."

Safety Concerns and Dosing Issues

The FDA's internal reviewers highlighted several issues in their briefing document prior to the meeting. They noted that GSK had not "adequately optimized" Blenrep's dosing, as evidenced by "high rates of ocular toxicity and poor tolerability." The reviewers also pointed out the "high rates of dose modifications" in both Phase III studies used to support GSK's application.

These concerns were echoed by the advisory committee members, who emphasized the need for better dosing strategies to mitigate the drug's toxicity profile while maintaining its efficacy.

Limited U.S. Patient Representation

Another significant issue raised during the meeting was the limited enrollment of U.S. patients in the clinical trials. Daniel Spratt of Case Western Reserve University highlighted this problem, stating, "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. It precludes any assessment of the benefit-risk profile in the U.S."

The FDA reviewers also noted limited enrollment of Black or African American patients and those 75 years of age and older, which may "limit applicability" of the results to U.S. patients.