FDA Grants Regular Approval to Venetoclax Combo for Older Adults with AML

The FDA has granted regular approval to venetoclax (Venclexta) in combination with azacitidine (Vidaza), decitabine, or low dose cytarabine (LDAC) for adults 75 years or older with newly diagnosed acute myeloid leukemia (AML), or who those have comorbidities precluding intensive induction chemotherapy.

Initially, the FDA granted accelerated approval to venetoclax for this indication in November 2018. Therefore, the efficacy of venetoclax was confirmed in 2 randomized, double-blind, placebo-controlled trials in the aforementioned patient population.

In the VIALE-A study (NCT02993523), patients were randomized to receive either venetoclax plus azacitidine (n = 286) or placebo plus azacitidine (n = 145). Efficacy was established based on improved overall survival (OS).

Median OS was 14.7 months (95% CI, 11.9-18.7) in patients treated with venetoclax plus azacitidine compared to 9.6 months (95% CI, 7.4-12.7) in those receiving placebo plus azacytidine, reducing the risk for death by 34% (HR, 0.66; 95% CI, 0.52-0.85; P < .001). Those treated with venetoclax plus azacitidine also demonstrated an improvement in complete remission (CR) rate, with 37% (95% CI, 31%-43%) experiencing a CR versus 18% (95% CI, 12%-25%) in the placebo arm.

Moreover, in the VIALE-C study (NCT03069352), patients were randomized to receive either venetoclax plus LDAC (n = 143) or placebo plus LDAC (n = 68). Efficacy was based on CR rate and duration of CR.

The CR rate in the venetoclax plus LDAC arm was 27% (95% CI, 20%-35%), compared with 8.3 months (95% CI, 3.1-not reached) in those receiving placebo plus LDAC. Median durations of CR were 11.1 months (95% CI, 6.1-not reached) and 7.4% (95% CI, 2.4%-16%), respectively. Of note, however, the addition of venetoclax did not significantly improve OS versus placebo plus LDAC (HR, 0.75; 95% CI, 0.52-1.07; P = .114).

The most common adverse events observed with venetoclax were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.

This review was conducted under Project Orbis, where the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic.

Further, using the real-time oncology review (RTOR) pilot program, and the assessment aid, the application for the venetoclax combination was approved 5 weeks ahead of the FDA PDUFA date.

Reference:

FDA grants regular approval to venetoclax in combination for untreated acute myeloid leukemia [news release]. FDA. Published October 16, 2020. Accessed October 16, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-venetoclax-combination-untreated-acute-myeloid-leukemia