General Information

Gazyva (obinutuzumab) is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B-cells.

Gazyva is specifically indicated for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia.

Gazyva is supplied as a solution for intravenous administration. The dose of Gazyva is 1000 mg, administered intravenously, with the exception of the first infusions in cycle 1, which are administered on day 1 (100 mg) and day 2 (900 mg). Gazyva is administered in six cycles, each consisting of 28 days.

Clinical Results

FDA Approval
The FDA approval of Gazyva was based on a three arm, open-label, active control, randomized, multicenter trial (Study 1) in 356 subjects with previously untreated CD20+ chronic lymphocytic leukemia requiring treatment and had coexisting medical conditions or reduced renal function. The subjects were treated with chlorambucil control (Arm 1), Gazyva in combination with chlorambucil (Arm 2) or rituximab in combination with chlorambucil (Arm 3). The safety and efficacy of Gazyva was evaluated in a comparison of Arm 1 vs. Arm 2. Data comparing Arm 2 vs. Arm 3 were not available at the time of approval. The majority of patients received 1000 mg of Gazyva on days 1, 8 and 15 of the first cycle, followed by treatment on the first day of 5 subsequent cycles (total of 6 cycles, 28 days each). The first dose of Gazyva was divided between day 1 (100 mg) and day 2 (900 mg). Chlorambucil was given orally at 0.5 mg/kg on day 1 and day 15 of all treatment cycles (1 to 6). The median progression free survival (PFS) in the Gazyva in combination with chlorambucil arm was 23.0 months versus 11.1 months in the chlorambucil alone arm. The Overall Response Rate was 75.9% versus 32.1%; the Complete Response was 27.8% versus 0.9% and the median duration of response was 15.2 months versus 3.5 months in the the Gazyva in combination with chlorambucil arm versus the chlorambucil alone arm, respectively.

Mechanism of Action

Gazyva (obinutuzumab) is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes. Upon binding to CD20, obinutuzumab mediates B-cell lysis through (1) engagement of immune effector cells, (2) by directly activating intracellular death signaling pathways and/or (3) activation of the complement cascade. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.