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, primarily driven by concerns over ocular toxicity and dosing issues, casts doubt on the drug's potential return to the American market.

ODAC's Concerns and Voting Outcome

During the July 17 meeting, ODAC members debated GSK's approval filing for Blenrep in combination with two different treatment regimens. The committee voted 5-3 against recommending Blenrep when combined with Takeda's Velcade and dexamethasone, and 7-1 against its pairing with Bristol Myers Squibb's Pomalyst and dexamethasone.

The primary concerns raised by the committee included:

1. High rates of ocular toxicity observed in GSK's phase 3 studies
2. Potential safety issues related to the proposed dosages
3. Lack of diversity in the demographics of enrolled patients, particularly the low representation of U.S. patients

Committee members emphasized that while GSK's efficacy data were strong, the toxicity data were equally compelling. Many voters cited the need for further work to determine an optimal dose that balances safety and efficacy.

Ocular Toxicity and Dosing Concerns

FDA reviewers had previously flagged "high rates of ocular toxicity" in GSK's pivotal DREAMM-7 and DREAMM-8 trials. The majority of patients in both studies experienced keratopathy and visual acuity events, with treatment associated with severe ocular toxicities such as corneal ulcers.

In the FDA's briefing document, reviewers noted that corneal toxicity is a "unique risk to this product and is not seen with currently available therapies" for multiple myeloma. The agency also raised concerns about the "high rates of dose modifications" observed in the studies, questioning whether the dosages evaluated in the DREAMM program were "adequately optimized."

Market Implications and Next Steps

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

While the FDA is not bound by the advisory committee's recommendation, the agency typically follows its guidance. The final decision on Blenrep's potential approval is expected by July 23.

Despite this setback in the U.S., Blenrep has already gained approval in the U.K. and Europe for the same proposed combinations. The drug's future in the American market now hinges on the FDA's final determination and GSK's ability to address the concerns raised during the ODAC meeting.