Venetoclax (Venclexta)

General information

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.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

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

Acute myeloid leukemia

• 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)

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

• 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