Under breakthrough therapy designation, FDA approves chronic lymphocytic leukemia drug

FDA has approved obinutuzumab (Gazyva, Genentech, a member of the Roche Group), also known as GA101, in combination with chlorambucil chemotherapy for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

Obinutuzumab is the first drug approved with FDA’s breakthrough therapy designation. FDA can designate a drug as breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. FDA also granted obinutuzumab priority review and orphan drug designation.

CLL is a blood and bone marrow disease that usually gets worse slowly. According to the National Cancer Institute, 15,680 Americans will be diagnosed and 4,580 will die from the disease this year.

Obinutuzumab works by helping certain cells in the immune system attack cancer cells. It is intended to be used with chlorambucil, another drug used to treat patients with CLL. 

The approval is based on the outcomes of the CLL11 trial. The trial showed that patients who received obinutuzumab in combination with chlorambucil chemotherapy had significantly reduced risk of disease progression or death (HR=0.16; P<.0001) and lived significantly longer without their disease getting worse compared to those who received chlorambucil alone (median PFS, 23.0 months vs 11.1 months). The most common Grade 3/4 adverse events for those who received obinutuzumab in combination with chlorambucil compared to chlorambucil alone were infusion-related reactions during the first infusion (21% vs. 0% [chlorambucil is an oral medicine]), thrombocytopenia (11% vs 3%) and neutropenia (34% vs 16%), though this did not result in an increased rate of infections in the obinutuzumab arm. 

Final data from the CLL11 trial investigating the direct comparison between obinutuzumab in combination with chlorambucil and rituximab (Rituxan) in combination with chlorambucil (stage 2) will be presented at the American Society of Hematology’s (ASH) 55th Annual Meeting in December 2013.

Obinutuzumab has a boxed warning regarding hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy). These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of obinutuzumab. Patients should be advised of these risks and assessed for hepatitis B virus and reactivation risk.