The panelists flagged safety concerns with Blenrep and GSK’s failure to optimize its dosing regimen for the antibody-drug conjugate in multiple myeloma.
The FDA’s external cancer advisors found that the benefits of GSK’s antibody-drug conjugate Blenrep to patients with relapsed or refractory multiple myeloma do not outweigh its risks.
The Oncologic Drugs Advisory Committee convened Thursday to vote on two proposed Blenrep combo regimens. With a 7–1 split, the panel agreed that Blenrep plus the chemotherapy pomalidomide and steroid dexamethasone had an unfavorable benefit-risk profile for this indication, while they voted 5–3 against the combination of Blenrep with bortezomib, another chemotherapy, and dexamethasone.
“The efficacy data were strong but the toxicity data were also very strong,” Neil Vasan, assistant professor at the Columbia University Medical Center, said in explaining his two no votes. “I really think this was just a missed opportunity over the course of many years of development of this drug to explore these different dosages.”
In a briefing document released ahead of the meeting, the FDA’s internal reviewers said that GSK had not “adequately optimized” its dosing for Blenrep, as illustrated by “high rates of ocular toxicity and poor tolerability.” The FDA reviewers also flagged the “high rates of dose modifications” in both Phase III studies used by GSK to support its Blenrep application.
The briefing document also pointed out that “in both trials, there was limited enrollment in the U.S., and limited enrollment of Black or African American patients and those 75 years of age and older,” noting that this may “limit applicability” of the results to U.S. patients.
Daniel Spratt of Case Western Reserve University raised the same demographic issue on Thursday. “This is the United States FDA, so the proposed patient population [are] the United States patients. The clinical development program enrolled almost no patients in the United States,” he said. “It precludes any assessment of the benefit-risk profile in the U.S.”
Blenrep was first approved in August 2020 for patients with relapsed or refractory multiple myeloma under the regulator’s accelerated pathway but was pulled from the market in November 2022 after it failed the confirmatory Phase III DREAMM-3 trial. Last year, however, GSK began plotting Blenrep’s comeback with data from the Phase III DREAMM-7 and DREAMM-8 trials, which demonstrated progression-free survival improvements after treatment with the drug.
The pharma in June 2024 even indicated that Blenrep could hit “multi-blockbuster” status when positioned as a second-line treatment for multiple myeloma.
