Venetoclax for CLL Granted Breakthrough Therapy Designation

Venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2) protein, is getting the green light from US Food and Drug Administration (FDA).

Venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2) protein, is getting the green light from US Food and Drug Administration (FDA). On May 6, 2015, it was granted Breakthrough Therapy Designation by the FDA for the treatment of chronic lymphocytic leukemia (CLL) in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation. Formerly known as ABT-199, venetoclax may help with the treatment of several other cancers as well.1

The developer of this agent AbbVie, a global biopharmaceutical company, hopes to submit regulatory applications for this new therapy to the FDA and the European Medicines Agency (EMA) within the next 7 months. Michael Severino, MD, executive vice president of research and development and chief scientific officer for AbbVie, said the new designation supports the continued development of this promising investigational medicine. He noted that there is a serious unmet clinical need in this patient population and mortality rates are high.

The BCL-2 protein prevents apoptosis of some cells, including lymphocytes. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Studies show that BCL-2 proteins are expressed at high levels in CLL, non-Hodgkin lymphoma (NHL), and in other cancers caused by B-cells. Venetoclax is currently being studied in phase II and phase III studies for CLL, and in phase I/II studies for several other blood cancers.

The new designation is intended to expedite the development of venetoclax. To receive this designation, a therapy must meet specific criteria, which include preliminary clinical evidence demonstrating it is a substantial improvement on at least one clinically significant endpoint compared to current available therapy. Another benefit associated with breakthrough therapy designation status is that it conveys all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program. Venetoclax is being developed in collaboration with Genentech and Roche.

CLL accounts for approximately 25% of the new cases of leukemia diagnosed in the United States, and approximately 3% to 10% of CLL patients have the 17p deletion at diagnosis. This specific deletion occurs in 30% to 50% of patients with relapsed/refractory CLL. The median life expectancy for CLL patients with the 17p deletion is less than 3 years.