Venetoclax, (brand names Venclexta and Venclyxto) is an oral medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).
Venetoclax attaches to the protein Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines.
By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease.
Common side effects include neutropenia, nausea, anemia, diarrhea, upper respiratory tract infection, fatigue, and thrombocytopenia (low platelet count). Major adverse effects include tumor lysis syndrome and severe neutropenia. Additionally, this drug may cause fertility problems in males.
Venetoclax Mechanism of Action
Venetoclax is a BH3-mimetic1. Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to chemotherapy.
The maximum plasma concentration achieved after oral administration occurred 5–8 hours after dose. Steady state maximum concentration with low-fat meal conditions at the 400 mg once daily dose was found to be 2.1 ± 1.1 μg/mL2.
Roberts AW, Huang D (January 2017). Targeting BCL2 With BH3 Mimetics: Basic Science and Clinical Application of Venetoclax in Chronic Lymphocytic Leukemia and Related B Cell Malignancies. Clinical Pharmacology and Therapeutics. 101 (1): 89–98. ↩︎
Kirsten Fischer, Anna-Maria Fink, Helen Bishop, Mark Dixon, Jasmin Bahlo, Michael Y. Choi, Robert Weinkove, K. Sue Robinson, Martin Dreyling, Till Seiler, Stephen Opat, Carolyn Owen, Javier Lopez, Nadine Kutsch, Eugen Tausch, Matthias Ritgen, Rod A. Humerickhouse, Kathryn Humphrey, Michael K. Wenger, Valentin Goede, Barbara Eichhorst, Clemens-Martin Wendtner, Stephan Stilgenbauer, Thomas J. Kipps, Michael Hallek. Results of the Safety Run-in Phase of CLL14 (BO25323): A Prospective, Open-Label, Multicenter Randomized Phase III Trial to Compare the Efficacy and Safety of Obinutuzumab and Venetoclax (GDC-0199/ABT-199) with Obinutuzumab and Chlorambucil in Patients with Previously Untreated CLL and Coexisting Medical Conditions. Blood 2015; 126 (23): 496. ↩︎