FDA News

FDA places partial clinical hold on venetoclax trials for multiple myeloma

The FDA placed a partial clinical hold on trials designed to evaluate venetoclax for the treatment of multiple myeloma, according to the drug’s manufacturer.

The agency’s decision came after a review of the ongoing randomized phase 3 BELLINI trial — which included patients with relapsed or refractory myeloma — showed a higher proportion of deaths among patients assigned venetoclax (Venclexta; AbbVie, Genentech) than placebo.

“We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial,” Michael Severino, MD, vice chairman and president of AbbVie, said in a company-issued press release. “We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the multiple myeloma program. We will continue to further the research and development of venetoclax and other therapies with the potential to transform the standards of care in blood cancers.”

The multicenter, double-blind BELLINI trial evaluated bortezomib (Velcade; Millennium/Takeda) and dexamethasone plus either venetoclax or placebo for patients with relapsed or refractory myeloma who received one to three previous lines of therapy and either were sensitive to or naive to proteasome inhibitors.

The study met its primary endpoint of improved PFS in the venetoclax group (median, 22.4 months vs. 11.5 months; HR = 0.63; 95% CI, 0.44-0.9). Results also showed a higher overall response rate (82% vs. 68%) and a higher rate of very good partial response or better (59% vs. 36%) in the venetoclax group.

However, researchers reported a higher rate of deaths (21.1% vs. 11.3%) and a higher rate of treatment-emergent deaths (6.7% vs. 1%) among patients treated with venetoclax. Investigators attributed eight of the 13 treatment-emergent deaths in the venetoclax group to an infection-related event, and more than half were in the setting of progressive or refractory disease.

The partial clinical hold means no new patients should be enrolled in studies of venetoclax for myeloma treatment until additional analyses of BELLINI trial data are completed.

Patients already enrolled in such studies who are deriving benefit from venetoclax may continue their treatment after consultation with their physician, according to the press release.

The partial clinical hold does not effect use of venetoclax for its approved indications, which include treatment of certain patients with chronic lymphocytic leukemia or acute myeloid leukemia.

The FDA placed a partial clinical hold on trials designed to evaluate venetoclax for the treatment of multiple myeloma, according to the drug’s manufacturer.

The agency’s decision came after a review of the ongoing randomized phase 3 BELLINI trial — which included patients with relapsed or refractory myeloma — showed a higher proportion of deaths among patients assigned venetoclax (Venclexta; AbbVie, Genentech) than placebo.

“We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial,” Michael Severino, MD, vice chairman and president of AbbVie, said in a company-issued press release. “We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the multiple myeloma program. We will continue to further the research and development of venetoclax and other therapies with the potential to transform the standards of care in blood cancers.”

The multicenter, double-blind BELLINI trial evaluated bortezomib (Velcade; Millennium/Takeda) and dexamethasone plus either venetoclax or placebo for patients with relapsed or refractory myeloma who received one to three previous lines of therapy and either were sensitive to or naive to proteasome inhibitors.

The study met its primary endpoint of improved PFS in the venetoclax group (median, 22.4 months vs. 11.5 months; HR = 0.63; 95% CI, 0.44-0.9). Results also showed a higher overall response rate (82% vs. 68%) and a higher rate of very good partial response or better (59% vs. 36%) in the venetoclax group.

However, researchers reported a higher rate of deaths (21.1% vs. 11.3%) and a higher rate of treatment-emergent deaths (6.7% vs. 1%) among patients treated with venetoclax. Investigators attributed eight of the 13 treatment-emergent deaths in the venetoclax group to an infection-related event, and more than half were in the setting of progressive or refractory disease.

The partial clinical hold means no new patients should be enrolled in studies of venetoclax for myeloma treatment until additional analyses of BELLINI trial data are completed.

Patients already enrolled in such studies who are deriving benefit from venetoclax may continue their treatment after consultation with their physician, according to the press release.

The partial clinical hold does not effect use of venetoclax for its approved indications, which include treatment of certain patients with chronic lymphocytic leukemia or acute myeloid leukemia.