FDA requires partial hold on trials for Venclexta

AbbVie has announced the FDA has placed a partial clinical hold on all clinical trials evaluating venetoclax (Venclexta /Venclyxto) for the investigational treatment of multiple myeloma. The partial clinical hold follows a review of data from the ongoing Phase III BELLINI trial (M14-031), a study in relapsed/refractory multiple myeloma, in which a higher proportion of deaths was observed in the venetoclax arm compared to the control arm of the trial. As a result of this action, no new patients should be enrolled in any studies of venetoclax for multiple myeloma until a further analysis of the data is completed. Patients who are currently enrolled in studies and receiving benefit from the therapy may continue with treatment, after consultation with their physician. This action does not impact any of the approved indications for venetoclax, such as chronic lymphocytic leukemia (CLL) or acute myeloid leukemia (AML), and is limited to investigational clinical trials in multiple myeloma. AbbVie remains confident in the benefit/risk profile of venetoclax in those approved indications. AbbVie has informed clinical trial investigators involved in the studies evaluating venetoclax for the treatment of multiple myeloma of the results and will work with them to proceed as appropriate and in the best interest of each patient who may be receiving benefit from venetoclax and who elects to continue receiving treatment. Additional analyses are ongoing, and data will be published in a peer-reviewed journal and/or presented at a future medical meeting. Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About BELLINI : BELLINI is a multicenter, randomized, double blind study of bortezomib and dexamethasone in combination with either venetoclax or placebo in patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy and are sensitive or naïve to proteasome inhibitors. The BELLINI study met its primary endpoint of progression-free survival (22.4 months vs. 11.5 months, hazard ratio [HR] 0.63, 95% confidence interval [CI]: 0.44-0.90) and demonstrated statistically significant improvements in overall response rate (82% vs. 68%) and very good partial response or better (59% vs. 36%) in the venetoclax arm compared to the control arm.

The details of the FDA review of the Phase III BELLINI study included the following safety updates: In a pre-planned analysis of the primary endpoint and ranked secondary endpoints, in the venetoclax arm 41 out of 194 (21.1%) deaths were observed, among which, 13 (6.7%) were treatment emergent (HR 2.03, 95% CI [1.042 – 3.945]). Of the 13 treatment-emergent deaths in the venetoclax arm, 8 were attributed by the investigator to an event of infection, and more than half were in the setting of refractory or progressive disease. In the placebo arm 11 out of 97 (11.3%) deaths were observed, among which, 1 (1.0%) was treatment emergent (occurred less than 30 days after last dose of study drug). The incidence of severe, grade 3-5 toxicity (86.5% vs. 87.5%, investigational vs. control arm) and serious adverse events (48.2% vs. 50.0%) was similar between the two arms. The incidence of infections (Infections and Infestation System Organ Class) was 79.8% in the investigational arm and 77.1% in the control arm. The incidence of pneumonia was 20.7% in the investigational arm and 15.6% in the placebo arm. Serious adverse events of infection were reported in 28.0% of patients in the investigational arm and 27.1% in the control arm. Serious adverse events of pneumonia were reported in 14.0% of patients in the investigational arm and 12.5% of patients in the placebo arm. Frequent causes of death not related to disease progression identified in the venetoclax arm were: sepsis, pneumonia, and cardiac arrest.