AHFS/Drugs.com venclexta ATC code L01XX52 (WHO) Protein binding >99.9% ChemSpider ID 29315017 | Routes ofadministration Oral (tablets) Legal status US: ℞-only Molar mass 868.44 g/mol | |
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Trade names Venclexta (US), Venclyxto (EU) Trade name Venclexta (US), Venclyxto (EU) | ||
Introducing venetoclax a powerful new drug that may treat cll
Venetoclax (INN, trade name Venclexta ven-KLEKS-tuh in the US and Venclyxto in Europe, is a small molecule oral drug that treats chronic lymphocytic leukemia (CLL) in those with a specific chromosomal abnormality. In 2015, the United States Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to venetoclax for subjects with CLL who have relapsed or have been refractory to previous treatment and have the 17p deletion genetic mutation.
Contents
- Introducing venetoclax a powerful new drug that may treat cll
- Venetoclax and ibrutinib and drug combinations for cll
- Medical uses
- Side effects
- Mechanism of action
- Pharmacokinetics
- History
- Society and culture
- Research
- References
Venetoclax and ibrutinib and drug combinations for cll
Medical uses
Venetoclax is used a second line treatment for chronic lymphocytic leukemia, only if there is a 17p deletion as determined by an approved test.
Side effects
Common side effects of venetoclax include neutropenia (low white blood cell count), nausea, anemia, diarrhea, upper respiratory tract infection, fatigue, and thrombocytopenia (low platelet count). Major side effects include tumor lysis syndrome and severe neutropenia. Additionally, this drug may cause fertility problems in males.
Mechanism of action
Venetoclax is a BH3-mimetic and acts as a Bcl-2 inhibitor. It blocks this 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.
Pharmacokinetics
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 ug/mL. It is recommended that Venetoclax be administered with a meal.
The apparent Volume of Distribution for Venetoclax is approximately 256-321 L. It is highly bound to human plasma protein. Within a concentration range of 1-30 μM (0.87-26 μg/mL), the fraction unbound in plasma was less than 0.01.
Venetoclax is metabolized by CYP3A4/5 as proven by in-vitro studies. Those using the drug should not consume grapefruit products because they contain CYP3A inhibitors. Additionally, while using venetoclax it is not recommended to use other drugs which contain CYP3A inhibitors (i.e: erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil.) Venetoclax is excreted from the body via the fecal route.
History
On April 11, 2016, the FDA approved venetoclax for use in those with CLL who have 17p deletion (deletion located on the chromosome 17 short arm) and who have been treated with at least one prior therapy. Based on overall response rate, the indication was approved under accelerated FDA approval.
In October 2016 a European Medicines Agency committee recommended provisional marketing approval for venetoclax for CLL; the drug had already been granted orphan status in 2012 for that use.
Society and culture
Abbvie Inc. of North Chicago Illinois manufactures Venclexta. It is marketed by both Abbvie Inc. and Genentech USA Inc. of South San Francisco, California, which is a member of the Roche Group. AbbVie and Genentech are both commercializing the drug within the United States, but only AbbVie has rights to do so outside of the U.S.
According to Reuters 2016 Drugs to Watch, the 2020 forecast sales for Venetoclax are 1.48 billion. Competition is expected from other drugs such as Imbruvica (ibrutinib) and Zydelig (idelalisib), both of which were also approved in 2014 to treat CLL (chronic lymphocytic leukemia).
Venclexta patented by Abbvie Inc. US Patent: 9,174,982.
Research
As of 2016 venetoclax had been tested to treat other hematological cancers, including non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma and follicular lymphoma.