Venetoclax

Analyst Outlook

Venetoclax (AbbVie/Roche) is a novel B-cell lymphoma-2 (BCL-2) inhibitor currently being developed

for treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). In May 2015, Roche

announced that the US Food and Drug Administration (FDA) had granted breakthrough therapy

designation for venetoclax in 17p deletion relapsed/refractory CLL (Roche press release, 2015). Early

clinical trials highlighted safety concerns after a patient death due to tumor lysis syndrome (AbbVie

press release, 2015b; Roberts et al., 2015). However, AbbVie/Roche have since modified the treatment

protocol, and no severe events of tumor lysis syndrome have occurred following this.

Drug Overview

Venetoclax is an inhibitor of the BCL-2 family of proteins. This family of proteins is responsible for the

regulation of cell death by either inducing or inhibiting apoptosis (Cory and Adams, 2002). Increased

expression of BCL-2 can lead to resistance to apoptosis in cancer cells. Venetoclax blocks the function

of the BCL-2 protein, leading to an increase in pro-apoptotic proteins and restoration of normal

apoptosis regulation (Souers et al., 2013).