In advance of this week’s adcomm, the FDA flags ocular toxicities associated with the antibody-drug conjugate, which received accelerated approval in August 2020 but was pulled from the market two years later after a confirmatory trial failed to improve progression-free survival.
FDA reviewers have flagged concerns about GSK’s data for its antibody-drug conjugate Blenrep, contending that the pharma has not established the drug’s efficacy and safety for relapsed or refractory multiple myeloma.
In a briefing document released Tuesday, regulators wrote that while two studies supporting GSK’s application for approval met their primary efficacy endpoints, “the high rates of ocular toxicity and dose modifications, coupled with limited dose exploration, necessitate a careful evaluation of the risks associated with [Blenrep]. The benefit-risk profile of [Blenrep] for the proposed indications . . . remains unclear.”
An advisory committee is scheduled to convene Thursday to discuss Blenrep’s application. The ADC was granted accelerated approval in August 2020 for relapsed or refractory multiple myeloma but in November 2022 failed to significantly improve progression-free survival (PFS) versus pomalidomide plus dexamethasone in the confirmatory Phase III DREAMM-3 study. GSK pulled Blenrep from the U.S. market two weeks later, and the FDA’s approval was withdrawn in February 2023.
Last year, however, GSK reignited Blenrep hopes with a series of late-stage readouts reinforcing the asset’s therapeutic potential in multiple myeloma. In February 2024, the pharma released data from the Phase III trial DREAMM-7, which found that the combination of Blenrep with Takeda’s Velcade led to significant PFS benefits in patients with relapsed or refractory disease. Additional data from the trial announced in December also showed that Blenrep outperforms Johnson & Johnson’s Darzalex in the second-line setting. GSK also presented data from DREAMM-8 last year, announcing in a June presentation that Blenrep bests a Velcade-based regimen in terms of PFS and treatment response.
Now, reviewers at the FDA are saying that while DREAMM-7 and DREAMM-8 showed efficacy in some groups, the data do not adequately establish the efficacy and safety of Blenrep for a broader U.S. population. “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,” which in turn may “limit applicability” of their findings to U.S. patients, according to the agency’s briefing document Tuesday.
The FDA noted toxicity issues related to patients’ eyes. The FDA called these ocular toxicities “unique,” noting that they are “not seen with any currently available treatments for multiple myeloma.”
GSK appears to also have not “adequately optimized” the dosing of Blenrep, according to the briefing document, as shown by the “high rates of ocular toxicity and poor tolerability” of the DREAMM-7 and DREAMM-8 doses. “On both trials, there were high rates of dose modifications.”
The FDA is asking external experts to decide whether GSK has identified an appropriate dose for Blenrep in the context of these toxicity and tolerability concerns.
Also on Tuesday, Fierce Biotech reported that GSK would be laying off a “very limited” number of employees across its global operations. The pharma declined to provide a specific number of staff affected and a timeline for these terminations. BioSpace has reached out to GSK for independent confirmation of this news.
