May 25, 2021: “Roche announced that the EU has approved Venclyxto® (venetoclax) in combination with hypomethylating agents, azacitidine and decitabine, for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.
“This Venclyxto approval is a critical step in providing new therapeutic options for patients in the EU newly diagnosed with AML who cannot tolerate the side effects of, or are ineligible for, intensive chemotherapy,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.
“Venclyxto-based combinations continue to show meaningful clinical benefits in AML patients, who would otherwise have a poor prognosis.”
The approval is based on the results of two key studies, phase III VIALE-A and phase I/II M14-358, of Venclyxto in combination with hypomethylating agents in adults with newly diagnosed AML, who are ineligible for intensive chemotherapy.
Results from the VIALE-A study showed Venclyxto plus azacitidine significantly reduced the risk of death by 34%, compared to azacitidine alone (HR=0.66; 95% CI: 0.52, 0.85; p<0.001).
The median overall survival was 14.7 months (95% CI: 11.9, 18.7) in the Venclyxto group and 9.6 months (95% CI: 7.4, 12.7) in the control group.
The Venclyxto combination more than doubled the complete responses (CRs), with a CR rate of 37% (95% CI: 31, 43) compared to 18% (95% CI: 12, 25) in the comparator arm (p<0.001).
The Venclyxto plus azacitidine combination also led to higher rates of composite complete remission (CR + CR with incomplete blood count recovery [CR + CRi]) at 66% (95% CI: 61, 72) compared to 28% (95% CI: 21, 36) with azacitidine alone (p<0.001).
The most frequently reported serious adverse reactions (≥5%) in patients receiving Venclyxto in combination with azacitidine were febrile neutropenia, pneumonia, sepsis and hemorrhage.
Results from the M14-358 study demonstrated that patients receiving Venclyxto in combination with decitabine achieved a CR + CRi rate of 74% (95% CI: 55, 88).
The most frequently reported serious adverse reactions (≥5%) were febrile neutropenia, pneumonia, bacteraemia and sepsis.
Today’s approval reinforces the potential of Venclyxto-based combinations to provide clinically meaningful benefits across several disease areas, including AML.
Venclexta® (venetoclax) is already approved in the US in combination with azacitidine, decitabine, or low dose cytarabine for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
Venclexta/Venclyxto is also approved in the US and EU in combination with MabThera®/Rituxan® (rituximab) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy; in combination with Gazyva®/Gazyvaro® (obinutuzumab) for the treatment of adult patients with previously untreated CLL; and as a monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor.
Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US, and commercialised by AbbVie outside of the US.
About the VIALE-A study
VIALE-A [NCT02993523] is a phase III, randomised, double-blind, placebo-controlled multicentre study evaluating the efficacy and safety of Venclyxto® (venetoclax) plus azacitidine, a hypomethylating agent, compared to placebo with azacitidine, in 431 people with previously untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy.
Two-thirds of patients (n=286) received 400 mg Venclyxto daily, in combination with azacitidine, and the remaining patients (n=145) received placebo tablets in combination with azacitidine.
Patients enrolled in the study had a range of mutational subtypes, including IDH1/2 and FLT3. VIALE-A met its primary and key secondary endpoints.
About the M14-358 study
M14-358 [NCT02203773] is a phase I/II, open-label, non-randomised, multicentre study evaluating the efficacy and safety of Venclyxto® (venetoclax) plus azacitidine or decitabine, in patients with previously untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy.
Oral Venclyxto was given in combination with azacitidine in 84 patients and in combination with decitabine in 31 patients.
