VENCLEXTA

What it is

VENCLEXTA contains venetoclax. It is available as film-coated tablets in 10 mg, 50 mg, and 100 mg strengths.

Approved indications

— Treatment of patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in combination with obinutuzumab. — Treatment of adult patients with previously untreated CLL/SLL in combination with ibrutinib. — Treatment of adult patients with CLL who have received at least one prior therapy in combination with rituximab. — Treatment of patients with relapsed or refractory CLL with 17p deletion as monotherapy. — Treatment of patients with relapsed or refractory CLL for whom there are no other suitable treatment options as monotherapy. — Treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy in combination with azacitidine or low-dose cytarabine.

Dosing overview

**Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma** VENCLEXTA is initiated at 20 mg once daily for 7 days, then escalated according to a weekly ramp-up schedule over 5 weeks to reach a daily maintenance dose of 400 mg. When used in combination with obinutuzumab, VENCLEXTA is given for a total of 12 cycles (28 days per cycle): 6 cycles in combination with obinutuzumab, followed by 6 cycles as a single agent. When used in combination with ibrutinib, the maintenance dose is 400 mg once daily with ibrutinib 420 mg orally once daily through Cycle 15. When used in combination with rituximab, VENCLEXTA 400 mg once daily continues for up to 24 months from initiation of rituximab in the absence of disease progression or unacceptable toxicity. **Acute Myeloid Leukaemia** The dose escalates from 100 mg on day 1 to 200 mg on day 2 and 400 mg from day 3 onwards when combined with azacitidine, or 600 mg from day 4 onwards when combined with low-dose cytarabine.

Key safety warnings

**Tumour Lysis Syndrome** Tumour lysis syndrome, including life-threatening or fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA. VENCLEXTA can cause rapid tumour reduction and poses a risk for tumour lysis syndrome in the initial 5-week ramp-up phase, with changes in electrolytes potentially occurring as early as 6 to 8 hours following the first dose and at each dose increase. Patients should be assessed for patient-specific factors determining risk level, and provided prophylactic hydration and anti-hyperuricaemic agents prior to the first dose of VENCLEXTA to reduce risk of tumour lysis syndrome. **Neutropenia** In patients with CLL/SLL, grade 3 or 4 neutropenia developed in 63% to 64% of patients and grade 4 neutropenia developed in 31% to 33% of patients treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients treated with VENCLEXTA in combination and monotherapy studies. Complete blood counts should be monitored throughout the treatment period, and dose interruptions or dose reductions are recommended for severe neutropenia. **Serious Infection** Serious infections, including events of sepsis and events with fatal outcome, have been reported in patients treated with VENCLEXTA. Patients should be monitored for fever and any symptoms of infection and treated promptly, with dosing interrupted as appropriate. **Live Attenuated Vaccines** Live attenuated vaccines should not be administered prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs.

Contraindications

VENCLEXTA is contraindicated in patients with hypersensitivity to venetoclax or to any of the excipients within the formulation. In patients with CLL or SLL, concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated.

PBS listing

VENCLEXTA 50 mg tablets are listed with 2 PBS items; VENCLEXTA 100 mg tablets are listed with 7 PBS items; VENCLEXTA 10 mg tablets are listed with 1 PBS item; and a combination pack containing 10 mg, 50 mg, and 100 mg tablets is listed with 4 PBS items. All listings require authority required restriction. The ex-manufacturer prices are A$12.07 for the 10 mg tablet, A$211.22 for the 50 mg tablet, A$7241.87 for the 100 mg tablet, and A$1563.04 for the combination pack.

Regulatory history

VENCLEXTA was first registered on the ARTG on 5 January 2017 with five product variants across different strengths and pack configurations. In July 2017, the PBAC recommended VENCLEXTA for relapsed or refractory CLL in patients who have failed a kinase inhibitor, on a cost-minimisation basis with idelalisib in combination with rituximab. In November 2017, the PBAC recommended extension to allow venetoclax in combination with rituximab for CLL in patients who have received at least one prior therapy. In November 2018, the PBAC recommended listing in combination with rituximab for relapsed or refractory CLL in patients unsuitable for treatment with a purine analogue. In July 2020, the PBAC recommended a change to allow first-line treatment in combination with obinutuzumab for CLL patients with coexisting conditions unsuitable for fludarabine-based chemotherapy. In July 2021, the PBAC recommended VENCLEXTA for acute myeloid leukaemia. The TGA approved VENCLEXTA for full registration for newly diagnosed AML in patients ineligible for intensive chemotherapy on 24 September 2021, following provisional registration and based on verification of benefit in confirmatory trials.