GSK's Blenrep Faces FDA Scrutiny Over Eye Safety Concerns Ahead of Potential U.S. Return

GSK's antibody-drug conjugate (ADC) Blenrep is under close examination by the U.S. Food and Drug Administration (FDA) as the company seeks to reintroduce the multiple myeloma treatment to the American market. The FDA has raised significant concerns about ocular toxicity and dosage optimization ahead of a crucial advisory committee meeting.

FDA Highlights Safety Concerns

In a briefing document released prior to the July 17 Oncologic Drugs Advisory Committee (ODAC) meeting, FDA reviewers emphasized "high rates of ocular toxicity" and "uncertainty regarding the proposed dosages" as key issues for discussion. The document revealed that in GSK's pivotal DREAMM-7 and DREAMM-8 trials, the majority of patients experienced Keratopathy and Visual Acuity (KVA) events, with grade 3-4 events occurring in 77% and 78% of patients, respectively.

The FDA noted that Blenrep's corneal toxicity is a "unique risk to this product and is not seen with currently available therapies" for multiple myeloma. Reviewers expressed concern about the potential impact on patient functioning and quality of life, stating that these toxicity issues, combined with high rates of dose modifications, raise questions about the adequacy of dosage optimization in the clinical trials.

GSK's Push for Approval

Despite these concerns, GSK is pursuing FDA approval for Blenrep in two combination therapies:

1. With Takeda's Velcade and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy.
2. In combination with Bristol Myers Squibb's Pomalyst and dexamethasone for patients who have tried at least one prior line of therapy, including BMS' Revlimid.

GSK's own briefing document highlighted the "clinically meaningful benefits" demonstrated in two independent, randomized Phase 3 studies. The company emphasized statistically significant improvements in overall survival from the DREAMM-7 study and argued that the efficacy data shows Blenrep's promise as an effective therapy in the evolving multiple myeloma treatment landscape.

Global Regulatory Landscape

While facing scrutiny in the U.S., Blenrep has seen recent success in other markets. Regulators in the U.K. approved Blenrep combinations in April, based on results from the DREAMM studies. In May, Europe's Committee for Medicinal Products for Human Use endorsed the Blenrep regimens for use in that region.

These regulatory wins have bolstered GSK's confidence in Blenrep's potential, with the company projecting peak sales of more than 3 billion pounds sterling (approximately $4 billion) for the ADC. This optimistic outlook has contributed to GSK's decision to raise its 2031 sales target to over 40 billion pounds.

As the pharmaceutical industry watches closely, the FDA's decision, expected by July 23, will play a crucial role in determining Blenrep's future in the U.S. market and its impact on GSK's ambitious sales projections.