FDA Accepts Application for Leukemia Drug Venetoclax

Compound targets apoptosis-inhibiting protein

The FDA has accepted a new drug application for venetoclax (AbbVie/Genentech/Roche) for the treatment of chronic lymphocytic leukemia (CLL) in adults who have received at least one prior therapy, including patients with the 17p deletion genetic mutation. The application was granted a priority review.

Venetoclax is an investigational oral B-cell lymphoma-2 (BCL-2) inhibitor being evaluated for the treatment of patients with various types of cancer. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be overexpressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is an investigational compound, and its safety and efficacy have not been evaluated by the FDA or any other health authority.

The FDA granted venetoclax breakthrough therapy status in April 2015 for the treatment of CLL in previously treated patients with the 17p deletion mutation, indicating the compound’s potential to provide substantial improvement over current therapies in this difficult-to-treat population.

The new drug application was supported by pivotal data from a phase 2, open-label study of venetoclax in patients with relapsed/refractory CLL with the 17p deletion mutation –– a genetic variation in CLL associated with a poor prognosis. In August 2015, AbbVie announced that the study had met its primary endpoint of achieving an overall response rate.

CLL is a slowly progressing cancer of the bone marrow and blood in which the bone marrow produces too many lymphocytes. It is the most common leukemia diagnosed in adults in western countries.

Chromosome 17 contains the TP53 gene, which is involved in regulating the division and death of normal cells. The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent. Approximately 3% to 10% of CLL patients have the 17p deletion mutation at diagnosis, and the mutation occurs in 30% to 50% of patients with relapsed/refractory CLL. The 17p deletion or mutations in TP53 are associated with rapid disease progression and short survival. The median life expectancy for CLL patients with the 17p deletion is less than two to three years.

Source: AbbVie; January 12, 2016.