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FDA Approval for Obinutuzumab

Brand name: Gazyva™

  • Approved for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL)

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications. 

On November 1, 2013, the Food and Drug Administration (FDA) approved obinutuzumab (Gazyva™ injection, for intravenous use, made by Genentech, Inc.; previously known as GA101) for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

The approval was based on demonstration of an improvement in progression-free survival (PFS) in a randomized open-label multicenter trial that compared obinutuzumab in combination with chlorambucil (GClb) with chlorambucil (Clb) alone in patients with previously untreated  CD20-positive CLL. The study also compared rituximab in combination with chlorambucil (RClb) with obinutuzumab in combination with chlorambucil (GClb). The results of the comparison of RClb with GClb will be available at a later stage.

Patients randomly assigned to be treated with obinutuzumab in combination with chlorambucil received 1000 mg doses of obinutuzumab intravenously on day 1 (later divided into 100 mg on day 1, followed by 900 mg on day 2), day 8, and day 15 of the first cycle. Chlorambucil, 0.5 mg/kg, was administered on days 1 and 15.  During treatment cycles 2-6, patients received obinutuzumab, 1000 mg intravenously only on day 1 in combination with chlorambucil, 0.5 mg/kg, on days 1 and 15. Patients received pre-medication with a glucocorticoid, acetaminophen, and antihistamine prior to initial obinutuzumab infusions and subsequently as needed. Patients assigned to be treated with single-agent chlorambucil received 0.5 mg/kg on days 1 and 15 of all treatment cycles (cycles 1 to 6). Cycles were repeated every 28 days.

A total of 356 patients were  randomly assigned (2:1) to receive obinutuzumab plus chlorambucil (n=238) or chlorambucil alone (n=118). The median age was 73 years (range 39 years-88 years). The independent review committee-assessed median PFS was 23.0 months for patients treated with obinutuzumab plus chlorambucil and 11.1 months for patients treated with  chloramucil alone [HR 0.16 (95 percent CI: 0.11, 0.24), log-rank p-value <0.0001]. 

The most common adverse reactions (at least 10 percent) with obinutuzumab plus chlorambucil (with a higher frequency than in the control arm) were infusion-related reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and musculoskeletal disorder. The most common grade 3-4 adverse reactions (at least 10 percent) were infusion-related reactions, neutropenia, and thrombocytopenia.

Infusion reactions occurred in 69 percent of patients receiving obinutuzumab; 21 percent experienced grade 3 or 4 reactions. Symptoms (greater than 10 percent) included dyspnea, hypotension, nausea, vomiting, chills, flushing, and pyrexia. 

Obinutuzumab is approved with a BOXED WARNING regarding Hepatitis B virus reactivation and Progressive Multifocal Leukoencephalopathy. Patients should be advised of these risks and assessed for Hepatitis B virus and reactivation risk. Infusion reactions are included in the WARNING and PRECAUTIONS section of the label.

The recommended dose and schedule for the approved regimen is:


Cycle 1: 100 mg intravenously on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15 

Cycles 2-6: 1000 mg administered intravenously every 28 days


0.5 mg/kg orally on days 1 and 15 of each cycle

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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  • Posted: November 1, 2013