BCL-2 Inhibitor Venetoclax Approved as Second Line for CLL With 17p Deletion

The approval comes following the review of a phase 2 single-arm trial in 106 patients with chronic lymphocytic leukemia who carried the 17p deletion mutation and who had received at least 1 prior therapy for their condition.

The FDA has approved venetoclax (to be sold as Venclexta), a B-cell lymphoma 2 or BCL-2 inhibitor, for the treatment of previously treated patients with chronic lymphocytic leukemia (CLL) who harbor a 17p deletion on their chromosome.

The most common type of leukemia in the United States, CLL, diagnosed in about 15,000 adults each year, is characterized by the accumulation of abnormal lymphocytes. The17p deletion— observed in 10% of untreated individuals diagnosed with CLL and 20% of relapsed patients—can result in uncontrolled cell growth due to the lack of a checkpoint.

The approval comes following the review of a phase 2 single-arm trial in 106 patients with CLL who carried the 17p deletion mutation and who had received at least 1 prior therapy for their condition. The trial measure overall response rate (ORR) and the duration of response (DOR) in these patients. An independent committee reviewed the outcome and confirmed that oral treatment of venetoclax, everyday over 5 weeks, presented an ORR of 80% (95% CI, 71%-87%), with 8% complete remission. The median time to first response was 0.8 months and the median DOR had not been reached at a 12 month follow-up.

“These patients now have a new, targeted therapy that inhibits a protein involved in keeping tumor cells alive,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “For certain patients with CLL who have not had favorable outcomes with other therapies, Venclexta may provide a new option for their specific condition.”

The FDA indication of this therapy is for the treatment of individuals with CLL who have a confirmed 17p deletion using the companion diagnostic Vysis CLL FISH probe kit. The molecular diagnostic kit has been approved by the FDA.

Developed by AbbVie Inc, venetoclax will be marketed by AbbVie and Genentech.