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

In a significant blow to GSK's efforts to reintroduce its multiple myeloma treatment Blenrep to the market, the U.S. Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) has voted against recommending approval for two proposed combination regimens. The panel's decision, based on concerns over safety and dosing optimization, casts doubt on the drug's future and its potential to achieve the "multi-blockbuster" status GSK had envisioned.

Advisory Committee's Unfavorable Vote

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 combination of Blenrep with pomalidomide and dexamethasone had an unfavorable benefit-risk profile. Similarly, the committee voted 5-3 against the combination of Blenrep with bortezomib and dexamethasone.

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 released prior to the meeting. They noted that GSK had not "adequately optimized" Blenrep's dosing, citing "high rates of ocular toxicity and poor tolerability." The reviewers also pointed out the "high rates of dose modifications" observed in both Phase III studies used to support GSK's application.

Daniel Spratt of Case Western Reserve University raised concerns about the limited enrollment of U.S. patients in the clinical trials, 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."

Blenrep's Rocky Path

Blenrep, an antibody-drug conjugate, has had a tumultuous history in the pharmaceutical market. Initially approved in August 2020 under the FDA's accelerated pathway for patients with relapsed or refractory multiple myeloma, the drug was voluntarily withdrawn from the market in November 2022 after failing to meet its primary endpoint in the confirmatory Phase III DREAMM-3 trial.

GSK attempted to revive Blenrep's prospects with data from the Phase III DREAMM-7 and DREAMM-8 trials, which demonstrated improvements in progression-free survival. The company had expressed optimism about Blenrep's potential as a second-line treatment for multiple myeloma, even suggesting it could achieve "multi-blockbuster" status.