FDA Approves Venclexta and Acalabrutinib Combination for Previously Untreated CLL Patients

The U.S. Food and Drug Administration has approved a supplemental new drug application for the combination regimen of Venclexta (venetoclax) and acalabrutinib for the treatment of previously untreated adult patients with chronic lymphocytic leukemia. The approval is supported by data from the Phase 3 AMPLIFY trial.

This milestone updates the treatment of CLL in the first-line setting, establishing the Venclexta and acalabrutinib combination as the first and only all-oral, fixed-duration regimen for previously untreated patients. The regimen supports current standards of care by offering patients the potential for time off treatment and giving providers a new, targeted option that combines two classes of oral medications for CLL.

AMPLIFY is an AstraZeneca-sponsored, global, multi-center Phase 3 trial evaluating Venclexta plus acalabrutinib alone or combined with obinutuzumab versus chemoimmunotherapy (investigator's choice of fludarabine-cyclophosphamide-rituximab [FCR] or bendamustine-rituximab [BR]) in patients with previously untreated CLL without del(17p) or TP53 mutation. Venclexta plus acalabrutinib were administered for a fixed duration of 14 cycles, each consisting of 28 days, while chemoimmunotherapy was administered for six cycles according to regimens. Venclexta was started on cycle 3 of 14 with a 5-week ramp-up schedule.

Results from the AMPLIFY study showed that the fixed-duration combination regimen of Venclexta and acalabrutinib was superior to FCR/BR chemoimmunotherapy. Study results showed the combination regimen of Venclexta and acalabrutinib reduced the risk of disease progression or death by 35% versus chemoimmunotherapy (HR 0.65; 95% CI: 0.49-0.87; p=0.0038). Median progression-free survival was not reached versus 47.6 months for chemoimmunotherapy.

The safety profile of the Venclexta and acalabrutinib combination regimen is consistent with the known safety profile of each individual therapy alone. In CLL/SLL, the most common adverse reactions (≥20%) for Venclexta when given in combination with acalabrutinib are neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19. The most common serious adverse reactions (≥2%) in patients receiving V+A were COVID-19, including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%). In patients treated with Venclexta plus acalabrutinib, the incidence of tumor lysis syndrome was 0.3%. No new safety signals were observed in the AMPLIFY study.

CLL is one of the most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes). While outcomes have improved in recent years, patients often face long treatment durations and ongoing disease management challenges.

Venclexta (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. Venclexta targets the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta 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. Venetoclax is approved in more than 80 countries, including the U.S.