Reviewing the Recent FDA Approval of Venclexta for AML

^{By Julie Gould}

Tony Lin, PharmD, senior scientific director, AbbVie US medical affairs, discusses the VIALE-A (M15-656) and VIALE-C (M16-043) trials, which helped determine the approval of Venclexta for acute myeloid leukemia, and highlights what this approval means for clinical practice.

Can you talk about the recent approval of Venclexta for acute myeloid leukemia (AML)? The approval was based on the VIALE-A (M15-656) and VIALE-C (M16-043) trials. What were some of these trial findings, and were any of them surprising?

The recent full FDA approval is supported by data from the Phase 3 VIALE-A (M15-656) and VIALE-C (M16-043) studies and updated data from the Phase 1b M14-358 and Phase 1/2 M14-387 studies.  

Viale-A was a randomized (2:1), double-blind, placebo-controlled, multicenter, phase 3 study that evaluated the efficacy and safety of venetoclax in combination with azacitidine (N=286) vs placebo with azacitidine (N=145) in adults with newly diagnosed AML who were ≥75 years of age, or had comorbidities that preclude use of intensive induction chemotherapy.  

The VIALE-A trial showed patients on the active regimen of venetoclax plus azacitidine achieved a 34% reduction in the risk of death compared to azacitidine in combination with placebo (P<0.001). The median OS for patients in the venetoclax arm was 14.7 months versus 9.6 months in the placebo arm. Additionally, patients in the venetoclax plus azacitidine arm achieved a CR rate of 37% (P<0.001) with a median duration of CR of 18.0 months compared with patients in the placebo plus azacitidine arm with a CR rate of 18% with a median duration of CR of 13.4 months. 

Viale-C was a randomized (2:1), double-blind, placebo-controlled, multicenter, phase 3 study that evaluated the efficacy and safety of venetoclax in combination with low dose cytarabine (LDAC; N=143) vs placebo with LDAC (N=68) in adults with newly diagnosed AML who were ≥75 years of age, or had comorbidities that preclude use of intensive induction chemotherapy.  

In the Viale-C trial, the median OS for VENCLEXTA in combination with LDAC was 7.2 months (95% CI: 5.6, 10.1) and 4.1 months for LDAC in combination with placebo (95% CI: 3.1, 8.8).  The improvement in OS was not statistically significant. Efficacy was based on the rate of complete remission (CR) and duration of CR with supportive evidence of rate of CR+CRh (CR + CR with partial hematologic recovery), duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. 

The observed safety profile of venetoclax plus azacytidine or LDAC was generally consistent with the known safety profile of both agents.

What does this approval mean for clinical practice? How will this approval change the future of care? 

In the VIALE-A trial, venetoclax in combination with azacitidine showed a significantly longer overall survival and lasting, durable remissions in newly-diagnosed AML patients 75 years or older or ineligible for intensive chemotherapy versus patients treated with azacitidine alone.  

Is there anything else you would like to add?  

For decades, there have been few options for patients with AML who cannot receive or tolerate intensive chemotherapy or a bone marrow transplant. The positive results from Viale-A and our recent FDA approval reflect our ongoing commitment to transform the standards of care for patients with hematologic malignancies.     

About Dr Lin

Tony Lin, PharmD, is senior scientific director with AbbVie US medical affairs, He is a pharmacist by training and has been working in the oncology therapeutic area and biopharmaceutical industry for over 12 years.