The antibody-drug conjugate, withdrawn from the market by GSK in 2022 after failing a confirmatory study, was approved Thursday by the FDA for previously treated patients with multiple myeloma. This is despite a negative advisory committee vote in July.
Despite a decidedly negative vote from an external panel of experts, the FDA has brought back GSK’s once-withdrawn antibody-drug conjugate Blenrep, approving its use for previously treated patients with relapsed or refractory multiple myeloma.
Blenrep has been approved for patients who have undergone at least two prior lines of therapy, in combination with bortezomib, a chemotherapeutic, and dexamethasone, a steroid.
This indication is slightly different than what GSK had been gunning for. In June 2024, Chief Commercial Officer Luke Miels told investors at an oncology-focused event the company was positioning Blenrep for a second-line comeback and touted its “multi-blockbuster” potential in this indication.
To back these aspirations, GSK leaned on data from the Phase III DREAMM-7 study, which compared a Blenrep-based regimen against Johnson & Johnson’s Darzalex plus bortezomib and dexamethasone. Results showed a progression-free and overall survival benefit with GSK’s ADC. Another trial, DREAMM-8, combined Blenrep with dexamethasone and pomalidomide. Results were likewise positive, leading to PFS and treatment response improvements over a similar regimen based on bortezomib.
The FDA’s internal reviewers, however, were not convinced. In a briefing document released in July this year, the agency’s staffers flagged “high rates of ocular toxicity and dose modifications” in Blenrep’s application, which they said “necessitate a careful evaluation of the risks associated” with the drug.
While Blenrep demonstrated efficacy in some groups, the reviewers continued, the data are insufficient to establish its clinical benefit for a broader U.S. population. “In both trials, there was limited enrollment in the U.S.,” the briefing document read, with the reviewers adding that GSK had also failed to recruit enough Black or African American patients and those 75 years and older.
An expert panel days later seconded these concerns. Voting 7–1 against Blenrep, the FDA’s Oncologic Drugs Advisory Committee found that the combination of Blenrep, pomalidomide and dexamethasone posed more risks than benefits for patients with previously treated multiple myeloma. Regarding the regimen with Blenrep, bortezomib and dexamethasone, the committee voted 5–3 against GSK.
The panelists echoed the FDA’s sentiments regarding enrollment, with Case Western’s Daniel Spratt saying “this is the United States FDA, so the proposed patient population [are] the United States patients.” GSK, he added, “enrolled almost no patients in the United States. It precludes any assessment of the benefit-risk profile in the U.S.”
A week after the panel’s meeting, the FDA delayed its target action date for a Blenrep decision from July 23 to Oct. 23.
Blenrep was initially approved in August 2020, likewise for relapsed or refractory multiple myeloma, under the FDA’s accelerated pathway. But after failing its confirmatory Phase III DREAMM-3 trial, the pharma decided to pull the product from the market in November 2022.
