FDA Approves Gazyva sBLA with New Data in Previously Untreated Chronic Lymphocytic Leukemia

Genentech has announced that FDA approved a supplemental biologics license application (sBLA) for Gazyva in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia (CLL). The sBLA adds to the label data from Stage 2 of the CLL11 study showing significant improvements with Gazyva plus chlorambucil across multiple clinical endpoints when compared head-to-head with Rituxan (rituximab) plus chlorambucil.

The approval includes complete response (CR) and minimal residual disease (MRD) data from Stage 2 of the study. Additionally, overall survival (OS) data was added from Stage 1 of the study comparing Gazyva plus chlorambucil to chlorambucil alone.

"Gazyva is the first and only medicine to significantly help people live without their disease worsening when combined with chlorambucil compared to Rituxan and chlorambucil in people with previously untreated chronic lymphocytic leukemia,” said Sandra Horning, MD, chief medical officer and head of Global Product Development. “These new data enhance our understanding of the disease and its treatment, and this approval affirms an important treatment option for people with this difficult-to-treat disease."

The sBLA approval updated the Gazyva prescribing information with the following data:

• Gazyva plus chlorambucil helped people with previously untreated CLL live nearly a year longer without their disease worsening or death (progression-free survival; PFS) than Rituxan plus chlorambucil (median PFS: 26.7 months vs. 14.9 months, respectively. HR=0.42, 95% CI 0.33-0.54, p<0.0001). 

• Gazyva plus chlorambucil nearly tripled the number of people showing no evidence of disease (CR) compared to Rituxan plus chlorambucil (26.1% vs. 8.8%, respectively).

• Of the people who achieved a complete response with or without complete recovery from abnormal blood cell counts (CR, CRi), 19% (18/94) of people in the Gazyva arm compared to 6% (2/34) of people in the Rituxan arm were MRD negative in the bone marrow, and 41% (39/94) of people in the Gazyva arm compared to 12% (4/34) people in the Rituxan arm were MRD negative in the peripheral blood. MRD negative means no residual traces of the cancer were found.

• Data from the first stage of the CLL11 study showed that at nearly 2 years, the rate of death was 9% (22/238) for people who received Gazyva plus chlorambucil compared to 20% (24/118) for those who received chlorambucil alone (HR=0.41, 95% CI 0.23-0.74). The median OS has not yet been reached.

Gazyva can cause serious or life-threatening side effects including: Hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), infusion reactions, tumor lysis syndrome, infections, and low white blood cell counts. The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

Gazyva, the first medicine approved with the FDA’s Breakthrough Therapy Designation, was approved for use in combination with chlorambucil in people with previously untreated CLL on 1 November 2013. Gazyva, known as Gazyvaro in Europe, was approved by the European Commission for the same indication in July 2014. Gazyva is also being investigated in a broad development program across various types of blood cancers, including multiple Phase III studies in non-Hodgkin’s lymphoma (NHL).