-- VENCLYXTO® (venetoclax) in combination with a hypomethylating agent is a new regimen approved by the European Commission (EC) for patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy [1]

-- Approval is based on data from AbbVie's clinical trial program for VENCLYXTO, including the Phase 3 VIALE-A trial, which showed patients treated with VENCLYXTO in combination with azacitidine demonstrated improvements in overall survival versus patients treated with placebo in combination with azacitidine [2]

-- Approval is also based on results of the Phase 1b M14-358 trial which showed patients treated with VENCLYXTO in combination with azacitidine or decitabine achieved high remission rates [3]

NORTH CHICAGO, Ill., May 25, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today that the European Commission (EC) has approved VENCLYXTO® (venetoclax) in combination with a hypomethylating agent, azacitidine or decitabine, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.1 The approval is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein, and Norway.

"VENCLYXTO has proven incremental overall survival in treating newly diagnosed AML in patients who are ineligible for intensive chemotherapy when treated with VENCLYXTO plus azacitidine compared to those treated with azacitidine alone," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "We look forward to bringing VENCLYXTO to more AML patients who can potentially benefit from this important new treatment option in EU countries."

 This is the third extension of indications for VENCLYXTO, a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 is a protein that prevents cancer cells from undergoing apoptosis, the process that leads to the natural death or self-destruction of cancer cells.1 

This most recent approval is based on results from the Phase 3 double-blind, placebo-controlled VIALE-A (M15-656) and the Phase 1b open-label, nonrandomized, multicenter M14-358 clinical trials. The VIALE-A trial demonstrated patients who received VENCLYXTO in combination with azacitidine showed statistically significantly greater median overall survival (OS) than patients receiving azacitidine alone (p=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.

Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions. 

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia. 

AML

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in combination with azacitidine or decitabine in the VIALE-A and M14-358, respectively, were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite, haemorrhage, dizziness/syncope, hypotension, headache, abdominal pain, and anaemia.

The most frequently reported serious adverse reactions (≥5%) in patients receiving venetoclax in combination with azacitidine were febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358, the most frequently reported serious adverse reactions (≥5%) were febrile neutropenia, pneumonia, bacteraemia and sepsis.

Discontinuations due to adverse reactions occurred in 24% of patients treated with venetoclax in combination with azacitidine in the VIALE-A study, and 26% of patients treated with venetoclax in combination with decitabine in the M14-358 study, respectively.

Dosage reductions due to adverse reactions occurred in 2% of patients in VIALE-A, and in 6 % of patients in M14-358. Venetoclax dose interruptions due to adverse reactions occurred in 72% and 65 % of patients, respectively. The most common adverse reaction that led to dose interruption (>10%) of Venetoclax in VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and thrombocytopenia. The most common adverse reactions that led to dose interruption (≥5%) of venetoclax in M14-358 were febrile neutropenia, neutropenia/neutrophil count decreased, pneumonia, platelet count decreased, and white blood cell count decreased.

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