FDA grants full approval to venetoclax for AML
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The FDA granted full approval to venetoclax in combination with azacitidine, decitabine or low-dose cytarabine to treat certain patients with newly diagnosed acute myeloid leukemia.
The full approval applies to adults aged 75 years or older, or those who are ineligible for intensive induction chemotherapy due to comorbidities.
Venetoclax (Venclexta; AbbVie, Genentech) — which selectively binds and inhibits the BCL-2 protein — received accelerated approval for this indication in 2018.
"For far too long, people with AML had very few treatment options, aside from very intense chemotherapy,” Lee Greenberger, PhD, chief scientific officer of The Leukemia & Lymphoma Society, said in an AbbVie-issued press release. “[This] news continues the progress of bringing more treatment options to patients with this devastating disease.”
Data from two randomized phase 3 trials — VIALE-A and VIALE-C — as well as updated data from the phase 1b M14-358 study and the phase 1/phase 2 M14-387 study supported the FDA approval.
The VIALE-A trial included 431 patients with AML who were ineligible for standard induction therapy. Researchers assigned 286 patients to venetoclax plus azacitidine. The other 145 patients received placebo plus azacitidine. OS served as the primary endpoint.
Interim analysis results showed significantly longer OS in the venetoclax-azacitidine group (median, 14.7 months vs. 9.6 months; HR = 0.66; 95% CI, 0.52-0.85).
A higher percentage of patients assigned venetoclax-azacitidine achieved complete remission (37% vs. 18%). Median durations of response were 18 months with venetoclax-azacitidine and 13.4 months with placebo-azacitidine.
The most common serious adverse events reported among patients treated with venetoclax-azacitidine included febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal, 19%) and hemorrhage (6%).
VIALE-C compared venetoclax plus low-dose cytarabine (n = 143) vs. placebo plus low-dose cytarabine (n = 68).
The study failed to meet its primary endpoint of significantly improved OS with venetoclax (median, 7.2 months vs. 4.1 months; HR = 0.75; 95% CI, 0.52-1.07).
However, the rate of complete remission (27% vs. 7.4%) and the rate of complete remission plus complete remission with partial hematologic recovery (47% vs. 15%) were higher in the venetoclax group. Median duration of complete remission was 11.1 months with venetoclax plus low-dose cytarabine vs. 8.3 months for placebo plus low-dose cytarabine.
The most frequent adverse event reported among patients assigned venetoclax plus low-dose cytarabine was nausea (42%). Sixty-five percent of patients assigned this combination experienced serious adverse events, the most common of which were pneumonia (17%), febrile neutropenia (16%) and sepsis (excluding fungal, 12%).
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