FDA approves Venclexta combo in acute myeloid leukaemia, despite it missing main study goal

The FDA has given approval to AbbVie and Roche’s jointly-developed BCL-2 inhibitor Venclexta (venetoclax) in combination with azacitidine, decitabine, or low-dose cytarabine as a treatment for newly-diagnosed acute myeloid leukaemia (AML) in patients at least 75 years old, or who have comorbidities that make the use of intensive induction chemotherapy inappropriate.  

The approval follows Venclexta securing accelerated approval from the FDA for this indication back in 2018, and the drug’s promising showing in AML based on interim analysis led AbbVie to submit its approval request early.

Data from a range of Phase 1-3 trials demonstrate that Venclexta plus azacitidine reduced risk of death by 34% over azacitdine plus placebo, with a median overall survival (OS) was 14.7 months in those receiving Venclexta compared to 9.6 months in those receiving placebo.

The Venclexta combo showed a complete remission rate of 37%, with that remission lasting a median of 18 months. This is compared to 18% with a median duration of 13.4 months in those receiving the azacytidine/placebo combo. Additionally, Venclexta plus low-dose cytarabine recorded a median OS of 7.2 months.

However, the therapy failed to generate a statistically significant OS improvement in AML patients who, at the time of analysis, were not eligible to receive intensive chemotherapy, falling swhort of the study’s primary goal. Despite this, the Venclexta group showed a higher rate of complete remission plus complete remission with partial haematologic recovery at 47% compared to 15%, while median duration of complete remission was shown to be 11.1 months with Venclexta combined with low-dose cytarabine versus 8.3 months for placebo plus low-dose cytarabine.

"AML is a complex and challenging disease with generally low survival rates,” explained Dr Mohamed Zaki, Vice President and Global Head of Oncology Development at AbbVie, adding that the data shows, “that newly-diagnosed patients, who cannot undergo intensive chemotherapy, lived longer when treated with Venclexta plus azacitidine than those treated with azacitidine alone. This trial also provides physicians more information for managing patients – from treatment initiation, to assessing response and management post disease remission."

Matt Fellows