GSK's Blenrep Faces FDA Scrutiny Over Eye Safety Concerns Ahead of Potential US Return

GSK's antibody-drug conjugate (ADC) Blenrep is under intense scrutiny as it seeks to re-enter the US market, with the FDA raising significant concerns about ocular toxicity. The pharmaceutical giant's efforts to bring the multiple myeloma treatment back to patients worldwide face a critical juncture as regulators and advisory committees prepare to evaluate new clinical data.

FDA Highlights Ocular Safety Issues

In a briefing document released ahead of 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 discussion points. The document revealed that in GSK's pivotal DREAMM-7 and DREAMM-8 trials, over 90% of patients experienced Keratopathy and Visual Acuity (KVA) events, with grade 3-4 events occurring in approximately 77-78% of patients.

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, questioning whether the dosages evaluated in the trials have been adequately optimized.

GSK's Case for Blenrep's Return

Despite these challenges, GSK remains optimistic about Blenrep's potential. The company is seeking FDA approval for two combination therapies:

1. Blenrep with Takeda's Velcade and dexamethasone for adults with multiple myeloma who've received at least one prior line of therapy.
2. Blenrep with Bristol Myers Squibb's Pomalyst and dexamethasone in patients who've 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 DREAMM-7 study showed a statistically significant improvement in overall survival, bolstering the company's case for Blenrep's efficacy.

Regulatory Landscape and Market Expectations

Blenrep's journey has been tumultuous since its original US approval in 2020 as a monotherapy for heavily pretreated multiple myeloma patients. After falling short in a confirmatory trial, GSK withdrew the drug from markets worldwide in 2022. However, recent regulatory wins in the UK and a positive opinion from Europe's Committee for Medicinal Products for Human Use have rekindled hope for the ADC's comeback.

GSK has set ambitious expectations for Blenrep, projecting peak sales of over 3 billion pounds sterling (approximately $4 billion). This forecast has played a role in the company's decision to raise its 2031 sales target to more than 40 billion pounds.

As the pharmaceutical industry watches closely, the FDA's decision, expected by July 23, will likely have far-reaching implications for both GSK and patients seeking new treatment options for multiple myeloma.