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Genentech’s Gazyva Gets Green Light in CLL

By Marie Powers
Staff Writer

Genentech Inc.’s Gazyva (obinutuzumab), formerly known as GA101, became the first therapy approved through the FDA’s breakthrough therapy designation, indicated in combination with chlorambucil to treat previously untreated chronic lymphocytic leukemia (CLL).

Approval was widely expected after Genentech, a unit of the Roche Group, reported in July that Gazyva beat Rituxan (infliximab, Roche AG and Biogen Idec Inc.) in a Phase III study in previously untreated CLL, becoming the first compound to show improvement over Rituxan head-to-head. (See BioWorld Today, July 25, 2013.)

The FDA green light likely marked the end of an era for the blockbuster Rituxan franchise, which earned $303 million for Biogen in the third quarter ending Sept. 30.

Gazyva is a glyco-engineered, Type II, humanized anti-CD20 monoclonal antibody designed to selectively target the CD20 protein on malignant B cells. By modifying specific sugar molecules, the antibody essentially functions as an immunotherapeutic. In preclinical studies, the drug showed evidence of binding to CD20 and inducing direct cell death.

Gazyva’s clinical development program, managed by Roche, was crafted specifically to assess superiority to Rituxan in CLL and non-Hodgkin's lymphoma (NHL). The multicenter, open-label, randomized three-arm CLL11 study investigated the efficacy and safety of Gazyva vs. Rituxan, both in combination with chlorambucil, compared to chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions.

The trial showed that patients who received Gazyva/chlorambucil had significantly reduced risk of disease progression or death (HR=0.16; p<0.0001) and lived twice as long without disease progression compared to chlorambucil alone (median progression-free survival 23 months vs. 11.1 months).

Gazyva also showed an acceptable safety profile. The most common Grade 3/4 adverse events for those who took Gazyva in combination with chlorambucil – an oral drug – compared to chlorambucil alone were infusion-related reactions during the first infusion (21 percent vs. 0 percent), low platelet count (thrombocytopenia, 11 percent vs. 3 percent) and low count of certain types of white blood cells (neutropenia, 34 percent vs. 16 percent), though this did not result in an increased rate of infections in the Gazyva arm.

South San Francisco-based Genentech said final data from Stage 2 of the CLL11 trial, which investigated the direct comparison between Gazyva and Rituxan, will be presented next month at the American Society of Hematology’s annual meeting. Stage 2 enrolled an additional 192 patients to enable final direct comparison. Although the company still has not disclosed details, in July company spokesman Joseph St. Martin said "final data were reached ahead of 2014 target completion date as a result of the magnitude of difference between study arms.”

Gazyva remains in multiple head-to-head Phase III studies compared to Rituxan in indolent NHL and diffuse large B-cell lymphoma.

The drug will be available in the U.S. within approximately two weeks, according to Genentech, which did not disclose pricing but plans to offer assistance programs for qualified patients.

See Monday's BioWorld Today for More on This Story.