Generic Venetoclax Gains Final FDA Approval in CLL/SLL and Newly Diagnosed AML

The FDA has granted final approval to Alembic Pharmaceuticals' generic version of venetoclax (Venclexta) tablets for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).¹ The decision also covers use of venetoclax alongside azacitidine (Vidaza), decitabine, or low-dose cytarabine in adults with newly diagnosed acute myeloid leukemia (AML) who are at least 75 years of age or whose comorbidities rule out intensive induction chemotherapy.

The abbreviated new drug application (ANDA) covers 10-mg, 50-mg, and 100-mg tablets, and the approved product is therapeutically equivalent to the AbbVie reference drug. As a first applicant with a substantially complete ANDA containing a paragraph IV certification, Alembic may qualify for 180 days of generic drug exclusivity.

What is the mechanism of action and recommended dosing of venetoclax?

Venetoclax selectively targets BCL-2, an antiapoptotic protein that promotes survival of CLL and AML cells when overexpressed and has been linked to chemotherapy resistance.² The oral small molecule binds BCL-2 directly and frees proapoptotic proteins such as BIM, which triggers mitochondrial outer membrane permeabilization and caspase activation.

The reference product's label calls for a 5-week ramp-up in CLL/SLL, with weekly doses of 20 mg, 50 mg, 100 mg, and 200 mg before reaching 400 mg once daily at week 5. In AML, doses escalate from 100 mg on day 1 to 200 mg on day 2 and 400 mg on day 3. From day 4, the daily dose is 400 mg when paired with azacitidine (75 mg/m² on days 1-7) or decitabine (20 mg/m² on days 1-5) and 600 mg when paired with low-dose cytarabine (20 mg/m² on days 1-10), each in 28-day cycles.

What data supported venetoclax plus oral decitabine/cedazuridine in AML?

The most recent indication approved for venetoclax arrived in May 2026, when the FDA approved decitabine and cedazuridine (Inqovi) plus venetoclax for the treatment of adult patients with newly diagnosed AML who are at least 75 years of age or who have comorbidities that preclude the use of intensive induction chemotherapy.³ This decision drew on data from he phase 1/2 ASCERTAIN-V trial (NCT04657081).

In the single-arm, open-label trial (n = 101), the FDA reported a complete response (CR) rate of 41.6% (95% CI, 31.9%-51.8%) and a median time to CR of 2 months (range, 0.4-15.3). The median duration of CR had not been reached (range, 0.5-16.3).

Data presented at the 2025 ASCO Annual Meeting showed that at a median follow-up of 11.2 months, the CR rate was 46.5% (95% CI, 36.5%-56.7%), and the median time to CR was 2.4 months.⁴ CR or CR with incomplete hematologic recovery occurred in 63.4% of patients (95% CI, 53.2%-72.7%), and CR or CR with partial hematologic recovery occurred in 51.5% (95% CI, 41.3%-61.6%). Response was maintained at 6 months in 80.0% of patients with a CR and at 12 months in 75.3%. Median overall survival reached 15.5 months (95% CI, 7.6-not estimable).

The recommended dose of decitabine/cedazuridine in the combination is 1 tablet containing 35 mg and 100 mg, respectively, once daily on days 1 to 5 of each 28-day cycle.³ In part B of the trial, venetoclax was escalated from 100 mg on day 1 to 200 mg on day 2 and 400 mg on days 3 to 5, then continued at 400 mg on days 6 to 28 of cycle 1 and days 1 to 28 of cycles 2 and 3. Therapy continued until disease progression, unacceptable toxicity, or withdrawal from the study.

What is the safety profile of venetoclax?

The reference product's label carries warnings and precautions for tumor lysis syndrome (TLS), neutropenia, infections, live attenuated vaccine use, and embryo-fetal toxicity.² It advises against combining venetoclax with bortezomib (Velcade) and dexamethasone in multiple myeloma outside of controlled clinical trials, citing increased mortality. Before starting venetoclax, patients with AML should have a white blood cell count below 25 × 10⁹/L, and hydration and antihyperuricemic prophylaxis should start before the first dose and continue through ramp-up. Blood chemistries should be checked for TLS before dosing, 6 to 8 hours after each new dose, and 24 hours after the final dose is reached.

Adverse effects (AEs) of any grade were reported in 99.0% of patients in ASCERTAIN-V (n = 101), and 80.2% had treatment-related AEs (TRAEs).⁴ Grade 3 or higher AEs affected 98.0% of patients, including grade 3 or higher TRAEs in 72.3%. Serious AEs affected 84.2%, including serious TRAEs in 35.6%.

Anemia was the most common TRAE (any grade, 32.7%; grade ≥3, 29.7%), followed by decreased platelet count (26.7%; 24.8%), neutropenia (25.7%; 25.7%), febrile neutropenia (24.8%; 24.8%), thrombocytopenia (21.8%; 19.8%), decreased neutrophil count (20.8%; 19.8%), nausea (19.8%; 0%), decreased appetite (17.8%; 1.0%), and decreased white blood cell count (14.9%; 14.9%). AEs prompted treatment interruption in 68.3% of patients, dose reduction in 13.9%, and discontinuation in 8.9%. Fatal AEs occurred in 15.8% of patients.

References

1. Alembic Pharmaceuticals Limited receives USFDA final approval for venetoclax tablets, 10 mg, 50 mg and 100 mg. News release. Alembic Pharmaceuticals Limited. October 30, 2026. Accessed November 3, 2026. https://alembicpharmaceuticals.com/webfiles/media/2026-2027/press-release-venetoclax-tablets-10-mg-50-mg-and-100-mg.pdf
2. Venclexta. Prescribing information. Updated May 2026. Accessed November 3, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/208573s032lbl.pdf
3. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. FDA. May 13, 2026. Accessed November 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-oral-combination-decitabine-and-cedazuridine-tablets-venetoclax-newly-diagnosed-acute
4. Zeidan AM, Griffiths EA, Dinardo CD, et al. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: results from a phase 2 cohort of 101 pts. J Clin Oncol. 2025;43(suppl 16):6504. doi:10.1200/JCO.2025.43.16_suppl.6504