Health Canada has approved Venclexta (venetoclax) in combination with Vidaza (azacitidine) or low-dose cytarabine to treat newly diagnosed adults, ages 75 and older, with acute myeloid leukemia (AML), who have other health conditions that make them ineligible for intensive chemotherapy.
This decision came about two months after the U.S. Food and Drug Administration (FDA) approved a series of Venclexta combinations for the same indication in the U.S. The Canadian agency’s decision was granted under Project Orbis, an FDA initiative that allows for the simultaneous submission and review of cancer treatments among several regulatory partner agencies worldwide.
“AML is one of the most common types of leukemia in adults. AML progresses rapidly and has a significantly lower survival rate compared to other cancers. Having more effective treatment options for AML patients will improve treatment outcomes for Canadians and extend lives,” Brian Leber, MD, head of the Leukemia Service at the Juravinski Hospital and Cancer Centre, said in a press release.
Developed by AbbVie and Roche and marketed as Venclyxto outside the U.S., Venclexta is a potent selective inhibitor of B-cell lymphoma-2 (BCL-2), a protein overproduced by cancer cells that normally prevents programmed cell death, or apoptosis. By blocking the activity of BCL-2, Venclexta is expected to prime cancer cells for apoptosis.
Approvals in the U.S. and Canada were supported by data from two confirmatory Phase 3 trials — VIALE-A (NCT02993523) and VIALE-C (NCT03069352) — that aimed to determine if the addition of Venclexta to chemotherapy (with either Vidaza or low-dose cytarabine) would be superior to chemo alone at prolonging the survival of newly diagnosed AML patients who did not qualify to be treated with intensive chemo.
In VIALE-A, 431 AML adults were randomly assigned to receive either oral tablets of Venclexta or a placebo, plus intravenous or subcutaneous (under-the-skin) injections of Vidaza.
Latest data from the study showed that after a median follow-up of 20.5 months (around two years), patients receiving the Venclexta combination therapy lived longer than those treated with chemo alone (14.7 vs. 9.6 months). This corresponded to a 34% reduction in patients’ overall risk of death.
In addition, a higher percentage of patients given the Venclexta-Vidaza combo achieved complete remission, that is, no longer showed signs of cancer (36.7% vs. 17.9%), and for longer periods of time (17.5 vs. 13.3 months).
All patients in the study experienced at least one adverse event. The incidence of side effects was slightly higher among those treated with the Venclexta-Vidaza combo than among those given Vidaza alone (83% vs. 73%).
Yet, the combination’s safety profile was found to be consistent with that of the individual medications, and side effects were expected based on the older population of AML patients participating in the study. The most common serious side effects observed in patients given the Venclexta combo therapy included low white blood cells counts accompanied with fever (30%), pneumonia (23%), sepsis (16%), and bleeds (9%).
In VIALE-C, 211 AML adults were randomly assigned to either oral tablets of Venclexta or a placebo, in combination with low-dose cytarabine given by a subcutaneous injection. For this specific combination, approval was granted based on the rate and duration of patients’ complete responses, rather than overall survival as in VIALE-A.
Data from VIALE-C showed that after a median follow-up of 12 months, a higher proportion of patients treated with the Venclexta-cytarabine combo achieved complete remission, compared with those given low-dose cytarabine alone (27.3% vs. 7.4%). These values were even higher considering all patients who saw their cancer being eliminated, regardless of achieving a complete normalization of other blood parameters (47.6% vs. 13.2%).
Remission periods also lasted longer in combination patients than in those treated with chemo alone (11.1 vs. 8.3 months).
The combination therapy’s safety profile was also found to be consistent with that of previous studies. The most frequent serious side effects observed in patients treated with the Venclexta-cytarabine combo included pneumonia (18%), low white blood cells counts accompanied with fever (16%), sepsis (11%), bleeds (9%), and low platelet counts (5%).
Health Canada’s decision to approve these Venclexta combinations for AML was welcomed by patients and the therapy’s developers, who stressed the high unmet need for treatments in this patient population.
“With limited treatment options, it makes me very happy to know that Venclexta has been approved to treat others, like me, who are diagnosed with AML,” William Levine, a patient living in Courtice, Ontario, said.
“Every day, we aim to transform the standard of care for people living with cancer. Having effective and proven treatment options is vital for patients and their families impacted by AML,” said Denis Hello, vice president and general manager of AbbVie Canada.
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