GSK's Blenrep Faces Setback in FDA Advisory Committee Review

GSK's efforts to bring its multiple myeloma antibody-drug conjugate (ADC) Blenrep back to the U.S. market have encountered a significant obstacle following a negative vote from the FDA's Oncologic Drugs Advisory Committee (ODAC). The committee's decision, based on concerns over ocular toxicity, dosing, and trial demographics, casts doubt on the drug's immediate future in the United States.

ODAC Vote and Key Concerns

On July 17, 2025, ODAC members convened to evaluate GSK's approval filing for Blenrep in combination with two different treatment regimens for multiple myeloma patients who have received at least one prior line of therapy. The committee voted 5-3 against recommending approval for Blenrep in combination with Takeda's Velcade and dexamethasone, and 7-1 against its pairing with Bristol Myers Squibb's Pomalyst and dexamethasone.

The primary issues raised by the committee included:

1. High rates of ocular toxicity observed in GSK's phase 3 DREAMM-7 and DREAMM-8 studies
2. Concerns over the proposed dosages and high rates of dose modifications
3. Limited U.S. patient enrollment in the trials, which comprised less than 5% of participants in each study

Ocular Toxicity and Dosing Challenges

FDA reviewers highlighted "high rates of ocular toxicity" as a key concern in their briefing document. The majority of patients in both DREAMM-7 and DREAMM-8 trials experienced keratopathy and visual acuity events, with 92% and 93% of patients affected, respectively. Grade 3-4 events occurred in 77% and 78% of patients across the two studies.

The agency noted that Blenrep was "associated with severe ocular toxicities, including corneal ulcers and clinically significant decline in visual acuity, including severe vision loss." This unique risk, not seen with currently available multiple myeloma therapies, raised concerns about the drug's impact on patient functioning and quality of life.

Market Implications and GSK's Response

The ODAC vote represents a significant setback for GSK, which had projected peak sales of more than 3 billion pounds sterling (approximately $4 billion) for Blenrep. The company's shares fell more than 5.5% following the announcement of the committee's decision.

Despite the negative vote, some committee members and public speakers emphasized the drug's potential benefits, particularly for patients with limited treatment options. John DeFlice, M.D., a patient representative and the sole voter in favor of both Blenrep combinations, described it as "an amazing drug for an incurable disease."

GSK now faces an uphill battle as it awaits the FDA's final decision, expected by July 23, 2025. While the agency is not bound by the advisory committee's recommendation, the vote adds significant uncertainty to Blenrep's prospects in the U.S. market.