Currently Enrolling Trials
Venclexta (venetoclax) is a BCL-2 inhibitor, an antiapoptotic protein.
Venclexta is specifically indicated for the following:
- 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;
- for use in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy
Venclexta is supplied as tablets for oral administration. Initiate therapy with Venclexta at 20 mg once daily for 7 days, followed by a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. Venclexta tablets should be taken orally once daily with a meal and water. Do not chew, crush, or break tablets.
Chronic Lymphocytic Leukemia
The FDA approval of Venclexta was based on an open-label, single-arm, multicenter clinical trial of 106 patients with CLL with 17p deletion who had received at least one prior therapy. Patients received Venclexta via a weekly ramp-up schedule starting at 20 mg and ramping to 50 mg, 100 mg, 200 mg and finally 400 mg once daily. Patients continued to receive 400 mg of Venclexta orally once daily until disease progression or unacceptable toxicity. The efficacy of Venclexta was evaluated by overall response rate (ORR) as assessed by an Independent Review Committee (IRC) using the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines. The ORR was 85%. The median time to first response was 0.8 months. Median duration of response (DOR) had not been reached with approximately 12 months median follow-up. The DOR ranged from 2.9 to 19.0+ months.
Acute Myeloid Leukemia
FDA approval was based on the results of two phase 3 studies: VIALE-A and VIALE-C.
VIALE-A: this randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of Venclexta plus azacitidine, a hypomethylating agent, compared to placebo with azacitidine, in 431 people with previously untreated acute myeloid leukemia who were ineligible for intensive chemotherapy. Two-thirds of patients (n=286) received 400 mg Venclexta daily, in combination with azacitidine, and the remaining patients (n=145) received placebo tablets in combination with azacitidine. Venclexta plus azacitidine significantly reduced the risk of death by 34% (overall survival; OS) compared to azacitidine alone (median OS=14.7 months vs. 9.6 months). People treated with Venclexta plus azacitidine had significantly higher rates of complete remission (CR) with 37% compared to 18% in people treated with azacitidine alone. The Venclexta plus azacitidine combination also led to higher rates of CR and CR with partial hematologic recovery (CR + CRh), with the combination showing a CR + CRh of 65% compared to 23% with azacitidine alone.
VIALE-C: this randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of Venclexta (venetoclax) plus LDAC, compared to placebo with LDAC, in 211 people with previously untreated acute myeloid leukemia who are ineligible for intensive chemotherapy. Two-thirds of patients (n=143) received 600 mg Venclexta daily in combination with LDAC and the remaining patients (n=68) received placebo in combination with LDAC. Twenty-seven percent of people treated with Venclexta plus LDAC achieved a CR (median duration of CR (DOCR)=11.1 months) vs. 7.4% of people treated with LDAC alone (median DOCR=8.3 months). The median OS for people treated with Venclexta plus LDAC was 7.2 months vs. 4.1 months for people treated with LDAC alone. These OS results were not statistically significant.
Adverse effects associated with the use of Venclexta may include, but are not limited to, the following:
- upper respiratory tract infection
Mechanism of Action
Venclexta (venetoclax) is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases.
For additional information regarding Venclexta or chronic lymphocytic leukemia, please visit https://www.venclexta.com/