|| Blood Cancer
|| Chronic Lymphocytic Leukemia (CLL) in presence of 17p deletion
| Mode of Action
|| BCL-2 inhibitor (chemotherapy)
| Approval Status
|| EMA approved (EU); FDA approved (USA); TGA approved (AUS)
| CAS Number || 1257044-40-8
| HS Code
|| 10 mg, 50 mg, 100 mg
Who is venetoclax for?
Venetoclax is indicated 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 . Venetoclax is marketed in the USA and in Australia under the name Venclexta, and in the Europen Union under the name Venclyxto.
Complete information about venetoclax dosage and administration can be found here .The recommended therapy consists of a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg.
Consult your treating doctor for personalised dosing.
- Week 1: 20 mg daily.
- Week 2: 50 mg daily.
- Week 3: 100 mg daily.
- Week 4: 200 mg daily
- Week 5+: 400 mg daily.
- The starter pack covers the treatment up to week 4. For week 5 and beyond venetoclax is dispensed as a one month supply in a bottle containing 120 100 mg-tablets.
- Concomitant use with strong inhibitors of CYP3A at initiation and during ramp-up phase is contraindicated .
What is venetoclax and how does it work?
Venetoclax is a BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion  or
patients with relapsed or refractory CLL when other medicines are unsuitable or have failed .
CLL is a slow-growing disease in which too many immature lymphocytes (white blood cells) accumulate in the blood and bone marrow 
. About 10 percent of patients with untreated CLL and approximately 20 percent of patients with relapsed CLL have a particular chromosomal abnormality (17p deletion) 
that is related to a specific type of CLL named B-Cell lymphoma 2 (BCL-2).
Patients with CLL who have a 17p deletion lack a portion of the 17th
chromosome where resides a gene involved with the identification and elimination of faulty cells 
. This gene thus acts to suppress cancer growth. In the presence of a 17p deletion, healthy cells are unable to use this identification/elimination pathway to prevent and control malignant cells 
.Venetoclax is a selective inhibitor of a protein, named B-Cell lymphoma 2 (BCL-2 protein), that inhibits cell death (anti-apoptotic protein). Overexpression of BCL-2 protein has been demonstrated in BCL-2 cells where it mediates tumour cell survival and has been associated with resistance to chemotherapeutics. Patients with 17p deletion usually have poor outcomes with conventional chemo-immunotherapy . Venetoclax is the first FDA-approved treatment that helps restore the process of apoptosis (cell death) by binding directly to the BCL-2 protein and preventing the inhibition of cell death .The presence of 17p deletion can be assessed through the use of the FDA-approved companion diagnostic Vysis CLL FISH probe kit . More information about the test can be found on the webpage of Abbott Molecular .
What is venetoclax's approval status?
Venetoclax was approved by
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 
- FDA (USA) on April 11, 2016
for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion or patients with relapsed or refractory CLL when other medicines are unsuitable or have failed .The FDA approval was based on a single-arm clinical trial of 106 patients with CLL who have a 17p deletion and who had received at least one prior therapy. Trial participants took venetoclax orally every day, beginning with 20 mg and increasing over a five-week period to 400 mg. Results showed that 80.2 percent (95% CI, (71.3, 87.3)) of trial participants experienced a complete or partial remission of their cancer (5.7% complete remission + 1.9% complete remission with incomplete marrow recovery). The median time to first response was 0.8 months (range: 0.1 to 8.1 months). The duration of response (DOR) ranged from 2.9 to 19.0+ months . Most common adverse reactions (≥20%) were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Venetoclax can cause rapid reduction in tumours and thus poses a risk for tumour lysis syndrome (TLS) in the initial 5 week ramp-up phase .
- EMA (EU) on December 5, 2016
- TGA (AUS) on January 05, 2017
The EMA approval was based on the fact that studies have shown that a high proportion of patients have their cancer cells partially or completely cleared following treatment with venetoclax. In a main study of 107 previously treated patients with CLL and 17p deletion, 75 % responded partially or completely to venetoclax. In another study of 64 patients with or without 17p deletion or TP53 mutation, the response rate was 67 %. Patients in this second study had all previously taken B‑cell receptor pathway inhibitors 
. The Australian approval was based on the first study, among others 
Summary of Product Characteristics [FDA]: Venclexta (venetoclax), AbbVie Inc., Apr. 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf
Anticancer Fund. Chronic lymphocytic leukemia. (last update: Aug. 2015), cited on 30/08/2016. http://www.anticancerfund.org/cancers/chronic-lymphocytic-leukemia
FDA News Release FDA approves new drug for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality, 11/04/2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm
Dr. Sharman's CLL & Lymphoma Blog. 17p Deletion in CLL, 15/10/2012. http://www.cll-nhl.com/2012/10/17p-deletion-in-cll.html#.V4eRXJN96u4
Patient Power. What exactly does a 17p deletion mean? (last updated: 6/04/2015), cited on 30/08/2016. https://www.patientpower.info/what-exactly-does-a-17p-deletion-mean
Jain N. and O'Brien S. Chronic Lymphocytic Leukemia With Deletion 17p: Emerging Treatment Options. Oncology. 15/11/2012. http://www.cancernetwork.com/oncology-journal/chronic-lymphocytic-leukemia-deletion-17p-emerging-treatment-options
Abbott. Vysis CLL FISH Probe Kit, cited on 30/08/2016. https://www.abbottmolecular.com/products/vysis-cll-fish-probe-kit-ce.html#OrderingInformation
Summary of Product Characteristics [EMA]: Venclyxto (venetoclax), AbbVie Ltd., Dec. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004106/WC500218800.pdf
Summary of Product Characteristics [TGA]: Venclexta (venetoclax), AbbVie Ltd., Jan. 2017. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01048-1
EMA. Human Medicines: Venclyxto (venetoclax), 21/12/2016, cited on Jan. 2016. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004106/human_med_002045.jsp&mid=WC0b01ac058001d124
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