Venetoclax
 | |
| Systematic (IUPAC) name | |
|---|---|
|
4-(4-{[2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl}-1-piperazinyl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide | |
| Clinical data | |
| Trade names | Venclexta |
| Routes of administration | Oral (tablets) |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Protein binding | >99.9%[1] |
| Metabolism | Hepatic (CYP3A4, CYP3A5) |
| Onset of action | Tmax = 5–8 hours |
| Biological half-life | ~26 hours |
| Excretion | Feces (>99.9%; 20.8% as unchanged venetoclax) |
| Identifiers | |
| CAS Number | 1257044-40-8 |
| PubChem | CID 49846579 |
| ChemSpider | 29315017 |
| KEGG | D10679 |
| Chemical data | |
| Formula | C45H50ClN7O7S |
| Molar mass | 868.44 g/mol |
| |
| |
Venetoclax (INN,[2] trade name Venclexta ven-KLEKS-tuh,[1] previously known as GDC-0199, ABT-199, and RG7601)[3] is a small molecule oral drug being investigated to treat chronic lymphocytic leukemia (CLL).[4][5][6] In 2015, the United States Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to venetoclax for patients with CLL who have relapsed or have been refractory to previous treatment and have the 17p deletion genetic mutation.[6]
Indications
On April 11, 2016, the FDA approved venetoclax for use in patients 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.[1][7]
Mechanism of action
Venetoclax is a BH3-mimetic[8] and acts as a Bcl-2 inhibitor. It blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells.[4]
Clinical trials
A phase I trial established a dose of 400 mg daily.[4]
A trial of venetoclax in combination with rituximab in subjects with CLL had an encouraging complete response rate.[9]
A phase II trial in subjects with CLL met its primary endpoint, which was overall response rate.[6] Interim results in 2015 from a Phase 2b trial were encouraging, especially in patients with the 17p deletion.[4]
Phase I and phase II trials for subjects with other types of cancers are ongoing.[10]
Two phase III trials for subjects with CLL, NCT02005471[3] and NCT02242942,[11] have been started, and are still recruiting subjects as of March 2016.[12]
References
- 1 2 3 "VENCLEXTA (venetoclax) Tablets, for Oral Use. U.S. Full Prescribing Information" (PDF). AbbVie Inc. Retrieved 14 April 2016.
- ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 111" (PDF). WHO Drug Information 28 (2): 270. 2014. Retrieved 14 April 2016.
- 1 2 New Drugs Online Report for venetoclax
- 1 2 3 4 Michael Smith (7 December 2015). "Hard-to-Treat CLL Yields to Investigational Drug". Medpage Today. Retrieved 23 March 2016.
- ↑ Roberts, Andrew W.; Davids, Matthew S.; Pagel, John M.; et al. (January 28, 2016). "Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia". New England Journal of Medicine 374 (5): 311–322. doi:10.1056/NEJMoa1513257. Retrieved 23 March 2016.
- 1 2 3 Press Release. "Phase 2 Study of Venetoclax in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia with 17p Deletion Meets Primary Endpoint". abbvie.mediaroom.com. Abbvie. Retrieved 24 March 2016.
- ↑ "FDA Approves New Drug for Chronic Lymphocytic Leukemia in Patients with a Specific Chromosomal Abnormality". U.S. Food and Drug Administration. Retrieved 14 April 2016.
- ↑ ABT-199 BH-3 Mimetic Enters Phase Ia Trial For Chronic Lymphocytic Leukemia. 2011
- ↑ Melville, Nancy A. "For Refractory CLL, Venetoclax's Complete Response Rate Is Tops". medscape.com. Medscape. Retrieved 23 March 2016.
- ↑ "Clinical Trials Search Results - Drug: venetoclax". cancer.gov. National Cancer Institute. Retrieved 24 March 2016.
- ↑ "A Study to Compare the Efficacy and Safety of Obinutuzumab + GDC-0199 Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia". clinicaltrials.gov. National Institutes of Health. Retrieved 24 March 2016.
- ↑ "A Study of GDC-0199 (ABT-199) Plus MabThera/Rituxan (Rituximab) Compared With Bendamustine Plus MabThera/Rituxan (Rituximab) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia". clinicaltrials. gov. National Institutes of Health. Retrieved 24 March 2016.
External links
- ABT-199 inc formula and structure