FDA Extends Review of Blenrep Combinations in Multiple Myeloma

The FDA has extended the review period for GSK’s biologics license application (BLA) for Blenrep (belantamab mafodotin-blmf) combinations to treat patients with advanced multiple myeloma. The new Prescription Drug User Fee Act (PDUFA) action date is Oct. 23, 2025, and provides the FDA with time to review additional information provided in support of the application.

Blenrep, in combination with Velcade (bortezomib) and dexamethasone, is being reviewed as a treatment for patients with relapsed or refractory multiple myeloma who have received at least one prior treatment.

Multiple myeloma is the second most common blood cancer in the United States and is generally considered treatable but not curable. In the United States, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year, and nearly 13,000 people will die from the disease.

Regulators delaying a decision on Blenrep comes just a week after an FDA advisory committee voted 5 to 3 against the risk-benefit profile of Blenrep in combination with Velcade (bortezomib) and dexamethasone. The committee also voted 7 to 1 against the risk-benefit profile of Blenrep in combination with Pomalyst (pomalidomide) and dexamethasone.

This submission for the combination therapy had been accepted by the FDA in November 2024. The BLA being reviewed by regulators is supported by efficacy results from the pivotal DREAMM-7 and DREAMM-8 phase 3 trials. These trials showed statistically significant and clinically meaningful progression-free survival results for Blenrep combinations versus triplet standard of care combinations and overall survival versus a daratumumab-based triplet in DREAMM-7.

The trials found that, with a median follow-up of 39.4 months, there was a statistically significant 42% reduction in the risk of death among patients receiving the Blenrep combination versus the daratumumab-based comparator. The three-year overall survival rate was 74% in the Blenrep combination arm and 60% in the daratumumab combination arm.

But regulators were concerned about the appropriate dose of Blenrep and about the ocular side effects. They asked the advisory committee to consider several issues outlined in a briefing document. In the document, regulators noted that “The key safety issue with belantamab mafodotin is ocular toxicity, including keratopathy (changes in the corneal epithelium), visual acuity changes, and other ocular symptoms, such as blurred vision and dry eye. While ocular adverse events have been seen with other antibody-drug conjugates used for the treatment of cancer, this toxicity is unique among therapies for the treatment of multiple myeloma.”

Regulators also noted poor tolerability with high rates of dose interruptions and dose reductions, with fewer than 50% of patients on each trial receiving the intended dose by cycle 3 of treatment.

In a news release, GSK officials said they remain confident in the benefit/risk profile of Blenrep. The PDUFA extension provides the FDA with time to review additional information provided in support of the application.

The FDA had originally granted accelerated approval of Blenrep as a monotherapy in August 2020 based on the DREAMM-2 endpoint of overall response rate. It was the first in a new class of drugs known as anti-BCMA (B-cell maturation antigen) monoclonal antibodies. The BCMA pathway has been shown to be important for myeloma cell growth and survival.

But in November 2022, GSK withdrew Blenrep from the U.S. market at the request of the FDA. The agency made the request after the DREAMM-3 phase 3 confirmatory trial failed to meet its endpoints.

Ocular adverse events had been identified in earlier research of Blenrep. Ocular adverse events, including blurred vision, dry eyes, eye pain, abnormal visual activity, and inflammation of the cornea, occurred in more than half of patients in DREAMM-1, an early study of Blenrep. Patients in the DREAMM-2 study were required to undergo monitoring for ocular events, and recommendations were to lower the dose of Blenrep, especially for those patients who were at risk.

Related: Researchers Gain Insight into Eye Side Effects of Blenrep

Researchers in a case analysis published recently in JAMA Ophthalmology found that the blood vessels around the cornea may be the primary pathway by which Blenrep causes ocular adverse events. In this analysis of nine patients, researchers found that Blenrep reaches corneal epithelial cells and is associated with pseudomicrocyst formation. Five samples were positive for apoptosis, and three samples showed evidence of inflammation. Antibody drug conjugate was detected in the tear fluid of 5 of 7 patients with tear fluid sampling, while ADC was quantifiable in 3 of 4 patients with blood samples.

Blenrep combinations are currently approved in the United Kingdom, Japan, Canada, Switzerland and the United Arab Emirates. Applications are currently under review in all major markets globally.