FDA approves Gazyva sBLA with new data in previously untreated CLL

FDA approved a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva, Genentech, a member of the Roche Group) in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia (CLL).

CLL is the most common type of adult leukemia; there are approximately 14,600 new cases each year in the United States. CLL is an incurable, chronic disease and increasing the time that people can live without the disease worsening is a goal of treatment.

The sBLA adds to the label data from Stage 2 of the CLL11 study showing significant improvements with Gazyva plus chlorambucil across multiple clinical end points when compared head-to-head with rituximab (Rituxan) plus chlorambucil. CLL11 is a phase 3, multicenter, open-label, randomized 3-arm study, conducted in cooperation with the German CLL Study Group, in 781 previously untreated people with CLL and co-existing medical conditions. Stage 1 (n=589) compared Gazyva plus chlorambucil to chlorambucil alone and Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyva plus chlorambucil directly with Rituxan plus chlorambucil. The primary endpoint of the study was PFS with secondary end points including overall response rate (ORR), OS, CR, median duration of response, MRD and safety profile. Results from Stage 2 and updated data from Stage 1 were presented in 2013 during the Plenary Scientific Session of the American Society of Hematology (ASH) meeting and published in the New England Journal of Medicine in 2014. 

“These CLL11 data added to the label further support Gazyva plus chlorambucil as an initial treatment option for CLL,” said Emmy Wang in Genentech Corporate Relations. “Gazyva is the first medicine that has shown an improvement in progression-free survival over rituximab in a phase 3, head-to-head study, when both are combined with chlorambucil.”

“Looking ahead, we have a broad Gazyva clinical study program that will help us better understand the potential safety and efficacy profile of Gazyva in different treatment settings and combinations, including multiple phase 3 studies in non-Hodgkin’s lymphoma [NHL],” Wang said.  

The approval includes complete response 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. 

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<.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 drug approved with FDA’s breakthrough therapy designation, was approved for use in combination with chlorambucil in people with previously untreated CLL on November 1, 2013.