GSK's Blenrep Faces Regulatory Hurdles in Multiple Myeloma Treatment

GSK's antibody-drug conjugate Blenrep (belantamab mafodotin) is under scrutiny as the FDA raises concerns about its efficacy and safety in treating relapsed or refractory multiple myeloma. The drug, which received accelerated approval in August 2020 but was withdrawn from the U.S. market in November 2022, is now seeking a comeback based on new clinical trial data.

FDA Flags Ocular Toxicity and Dosing Concerns

In a briefing document released ahead of this week's advisory committee meeting, FDA reviewers highlighted significant concerns about Blenrep's ocular toxicities, which they described as "unique" and "not seen with any currently available treatments for multiple myeloma." The high rates of ocular toxicity and dose modifications observed in clinical trials have led regulators to question whether GSK has adequately optimized the dosing of Blenrep.

The FDA is particularly concerned about the applicability of the trial results to the broader U.S. population, noting limited enrollment of Black or African American patients, those 75 years of age and older, and overall U.S. participants in the DREAMM-7 and DREAMM-8 trials.

Clinical Trial Results and Regulatory Implications

Despite these concerns, GSK has presented promising data from recent late-stage trials:

• The Phase III DREAMM-7 trial showed that Blenrep combined with Takeda's Velcade (bortezomib) led to significant progression-free survival (PFS) benefits in relapsed or refractory multiple myeloma patients.
• DREAMM-7 data also indicated that Blenrep outperforms Johnson & Johnson's Darzalex (daratumumab) in the second-line setting.
• The DREAMM-8 trial demonstrated Blenrep's superiority over a Velcade-based regimen in terms of PFS and treatment response.

However, the FDA maintains that these results do not adequately establish Blenrep's efficacy and safety for a broader U.S. population. The advisory committee scheduled for Thursday will discuss Blenrep's application and assess whether GSK has identified an appropriate dose in light of the toxicity and tolerability concerns.

Implications for GSK and the Multiple Myeloma Treatment Landscape

The outcome of this regulatory review could have significant implications for GSK and patients with relapsed or refractory multiple myeloma. If approved, Blenrep would offer a new treatment option for this difficult-to-treat patient population. However, the FDA's concerns about ocular toxicities and dosing optimization present substantial hurdles for GSK to overcome.

As the pharmaceutical industry closely watches the developments surrounding Blenrep, GSK faces the challenge of addressing the FDA's concerns while demonstrating the drug's potential benefits for multiple myeloma patients. The company's ability to navigate these regulatory challenges will be crucial in determining Blenrep's future in the U.S. market and its role in the treatment of multiple myeloma.