Previously known as GA101 or afutuzumab, obinutuzumab is a third generation, experimental, humanized antibody being investigated in a large clinical program, including studies comparing it with Rituxan for the treatment of chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).
How Obinutuzumab Works
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the human CD20 antigen present on the B cell surface in various B cell malignancies. The Fc region carbohydrates of the antibody, enriched in bisected non-fucosylated glycosylation variants, contribute to its higher binding affinity for human FcγRIII receptors compared to non-glycoengineered antibodies, which is believed to result in enhanced antibody-dependent cellular cytotoxicity (ADCC) and caspase-independent apoptosis. In pre-clinical development, obinutuzumab has shown evidence of increased direct cell killing and ADCC.
On January 30, 2013, Genentech/Roche announced positive results from Stage 1 of a Phase 3 trial in patients with previously untreated CLL that showed treatment with obinutuzumab plus chlorambucil significantly reduced the risk of disease worsening or death (progression-free survival or PFS) compared to treatment with chlorambucil alone. CLL patients treated with obinutuzumab and chlorambucil had a PFS of 23 months compared to 10.9 months for patients treated with chlorambucil only. Based on these data, Genentech/Roche filed for approval in US and EU for treatment of CLL in May 2013. Subsequently, FDA designated obinutuzumab as a breakthrough therapy for CLL and granted it priority review with a PDUFA date of December 20, 2013.
On July 23, 2013, Genentech/Roche announced results from a planned interim analysis of Stage 2 of this Phase 3 trial that showed CLL patients treated with obinutuzumab and chlorambucil lived significantly longer than patients receiving Rituxan and chlorambucil. While the differences in PFS will not be disclosed until the American Society of Hematology Annual Meeting in early December 2013, Genentech/Roche stated that the endpoint was achieved sooner than the target date of 2014 because of the magnitude of the benefit of treatment with obinutuzumab and chlorambucil.
PDL granted Glycart a license under the Queen et al. patents for the development of GA101. Glycart was acquired by Roche in 2005.