FDA Stops Enrollment in Phase 3 MM Trial Due to 2-Fold Increase in Mortality

This week, the FDA sent out an alert to various healthcare professionals and the public to warn about the risks associated with the investigational use of venetoclax (Venclexta) for the treatment of patients with multiple myeloma (MM). The alert is based on data from the ongoing phase 3 BELLINI trial evaluating the drug for this treatment.

Earlier this month, the FDA ordered AbbVie, developer of venetoclax, to halt enrollment in MM clinical trials evaluating the drug. “FDA reviewed data from the BELLINI clinical trial evaluating the use of Venclexta combined with bortezomib, a proteasome inhibitor, and dexamethasone in patients with [MM]. The interim trial results demonstrated an increased risk of death for patients receiving Venclexta as compared to the control group. On March 6, 2019, the FDA required no new patients be enrolled on the BELLINI trial,” according to an FDA press release. This suspension of enrollment extended to other ongoing MM clinical trials as well.

The FDA noted, however, that this alert does not apply to indications for which venetoclax is currently FDA approved, including chronic lymphocytic leukemia, small lymphocytic lymphoma, and as part of a combination treatment for acute myeloid leukemia. Additionally, patients currently enrolled in the BELLINI clinical trial who are receiving clinical benefit may continue the treatment after reconsenting.

Specifically, the FDA found that at the interim analysis for overall survival, there were 41/194 (21.1%) deaths found in the venetoclax arm compared with 11/97 deaths in the placebo arm (hazard ratio [HR], 2.03; 95% CI, 1.04-3.94), “increasing the relative risk of death by approximately [2]-fold compared to the placebo arm,” according to the FDA.

In a statement released by AbbVie prior to the publication of the FDA’s findings, Michael Severino, MD, vice chairman and president of AbbVie, said, “We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial. We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the [MM] program.”

The FDA encouraged healthcare professionals or patients to report any adverse events related to venetoclax to the FDA’s MedWatch Adverse Event Reporting program.