Roche and AbbVie Face Setback in Venclexta Trial for Myelodysplastic Syndromes

Roche and AbbVie announced on Monday that their phase 3 trial of Venclexta in patients with higher-risk myelodysplastic syndromes (MDS) failed to meet its primary endpoint of overall survival. This latest setback adds to a series of challenges the companies have faced in expanding indications for their blockbuster blood cancer treatment.

Trial Results and Implications

The global study, involving approximately 500 patients, tested the combination of Venclexta and azacitidine chemotherapy against placebo plus azacitidine in previously untreated patients with higher-risk MDS. Despite the disappointing outcome, the companies plan to present full data from the trial at an upcoming medical meeting.

This failure marks the second recent trial setback for Venclexta. In 2023, the drug fell short in the Canova study, which evaluated its efficacy in patients with relapsed or refractory multiple myeloma. Although the Venclexta regimen improved progression-free survival in that trial, the difference did not reach statistical significance.

Venclexta's History and Mechanism of Action

Venclexta, a first-in-class drug, works by selectively binding and inhibiting the B-cell lymphoma-2 protein, thereby restoring the process of apoptosis that is hindered in some blood cancers. The treatment first received FDA approval in 2016 for chronic lymphocytic leukemia, with subsequent approvals for acute myeloid leukemia (AML) in 2018 and 2020.

Despite these setbacks, Venclexta has maintained its blockbuster status, generating sales of $2.6 billion in 2024, a 13% increase from the previous year. However, the companies' efforts to expand its use have been met with significant challenges, including a clinical hold in 2019 due to increased mortality in a multiple myeloma trial.