Class/mechanism: From the NCI Drug Dictionary: An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. GDC-0199 mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.
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Diseases for which it is used
History of changes in FDA indication
- 11/21/2018: Accelerated approval for use in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. (New disease entity; based on M14-358 and M14-387)
- 10/16/2020: Regular approval in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities precluding intensive induction chemotherapy. (Converted to regular approval; based on VIALE-A and VIALE-C)
- 4/11/2016: Approved for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. (Initial approval; based on M12-175, M13-982, and M14-032)
- 6/8/2018: Granted regular approval for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. (Regular approval; Biomarker-specific indication relaxed; based on MURANO)
- 5/15/2019: Approved for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). (Prior treatment exposure requirement removed; based on GCLLSG CLL14)
Also known as
- Code names: ABT-199, GDC-0199
- Brand name: Venclexta