Based upon an agreement that study protocol would be revised, the FDA has removed the partial clinical hold it placed in March on CANOVA, a phase 3 clinical trial of venetoclax.
The FDA has removed the partial clinical hold it placed on AbbVie's CANOVA (M13-494) study, according to a statement from the company. CANOVA was designed to investigate venetoclax (Venclexta or Venclyxto) for the treatment of relapsed and refractory multiple myeloma (MM) patients with a specific genetic mutation.
Regulators lifted the partial clinical hold based upon an agreement that the study protocol would be revised. Changes included new risk mitigation measures, protocol-specified guidelines, and updated futility criteria. Researchers may now continue enrollment for the study based on the approved protocol.
CANOVA, a multicenter, randomized, open-label, phase 3 trial, was being conducted to examine the efficacy of venetoclax combined with dexamethasone, compared to pomalidomide combined with dexamethasone, in patients with relapsed and refractory MM who were positive for the translocation (11;14) abnormality. The t(11;14) biomarker is 1 of the most prevalent, regularly tested genetic abnormalities among patients with MM.
The FDA ordered the partial clinical hold on all venetoclax-related trials in March 2019 when results from the BELLINI study showed a disproportionate number of deaths had occurred among participants treated with venetoclax compared to the number of deaths that occurred among participants who received placebo.
BELLINI was a phase 3, randomized, double-blind, controlled trial of bortezomib and low-dose dexamethasone with or without venetoclax in patients with relapsed and refractory MM who previously received 1 to 3 lines of therapy. At the interim analysis for overall survival in BELLINI, there were 41 deaths reported among 194 patients in the venetoclax-treated study arm while 11 deaths were reported among 97 patients in the placebo-treated arm. Progressive disease was the most common cause of death in 45% of participants.
All other clinical trials involving venetoclax will continue to remain on partial clinical hold while the FDA continues to evaluate further steps. The hold doesn’t affect any of the previously approved indications for venetoclax. AbbVie stated they remain confident in the risk-benefit profile of venetoclax for the approved indications.
"We are pleased to move forward with the CANOVA study which, with the t(11;14) biomarker test, can help identify patients who may respond better to treatment and add clarity for physicians when choosing a therapy, if approved," said Mohamed Zaki, MD, PhD, global head of hematology development for AbbVie. "We are working closely with regulatory authorities worldwide to continue our efforts to understand the potential of venetoclax for patients with multiple myeloma while continuing to advance research in patients with the t(11;14) genetic abnormality."
FDA warns about the risks associated with the investigational use of Venclexta in multiple myeloma [new release]. United States Food and Drug Administration; March 21, 2019.
fda.gov/drugs/drug-safety-and-availability/fda-warns-about-risks-associated-investigational-use-venclexta-multiple-myeloma. Accessed June 24, 2019.