AbbVie announces US FDA approves combination treatment of Venclexta and acalabrutinib for previously untreated patients with CLL

AbbVie announced that the US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for the combination regimen of Venclexta (venetoclax) and acalabrutinib for the treatment of previously untreated adult patients with chronic lymphocytic leukaemia (CLL). 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.

"This FDA approval marks a significant milestone for AbbVie and, more importantly, for people living with CLL," said Svetlana Kobina, vice president, global medical affairs, oncology, AbbVie. "As the first and only all-oral, fixed-duration combination regimen for previously untreated patients, the Venclexta plus acalabrutinib approval expands choice and flexibility for patients and providers navigating complex treatment decisions in CLL."

CLL is one of the most common forms of leukaemia 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.

"With the FDA approval of the combination of venetoclax and acalabrutinib for use as a front-line therapy in CLL, patients in the USA now have an all oral, time-limited option that can be important for many in choosing their treatment," said Dr. Brian Koffman, co-founder and chief medical officer emeritus, CLL Society. "CLL Society is pleased to see the number of choices available for patients growing."

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 (PFS) 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 tumour lysis syndrome was 0.3%. No new safety signals were observed in the AMPLIFY study.

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 US and by AbbVie outside of the US. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the US.

Venclexta is a prescription medicine used:

• to treat adults with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).
• in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with
• newly diagnosed acute myeloid leukaemia (AML) who:
• are 75 years of age or older, or
• have other medical conditions that prevent the use of standard chemotherapy.