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
- Acute myeloid leukemia
- Chronic lymphocytic leukemia
- Mantle cell lymphoma
- Multiple myeloma
- T-cell prolymphocytic leukemia
- Waldenström macroglobulinemia
History of changes in FDA indication
- 2018-11-21: 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)
- 2020-10-16: 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)
- 2016-04-11: Initial accelerated approval 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. (Based on M12-175, M13-982, M14-032 ibrutinib cohort, and M14-032 idelalisib cohort)
- 2018-06-08: 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)
- 2019-05-15: Approved for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). (Prior treatment exposure requirement removed; based on GCLLSG CLL14)
History of changes in EMA indication
- 2016-12-04: Initial authorization as Venclyxto
History of changes in Health Canada indication
- 2016-09-30: Initial notice of compliance with conditions
- 2020-01-13: Conditions were met
History of changes in PMDA indication
- 2019-09-20: Newly indicated for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.
- 2021-03-23: New indication and a new dosage for the treatment of acute myeloid leukemia.
Also known as
- Code names: ABT-199, GDC-0199
- Brand name: Venclexta, Venclyxto