Gazyva

Drug Overview
Gazyva (obinutuzumab; Roche/Biogen/Chugai/Nippon Shinyaku) is a third-generation, type II glycoengineered, humanized anti-CD20 monoclonal antibody (MAb) that recognizes the type II epitope of the CD20 antigen expressed on the surface of pre-B and mature-B lymphocytes. Gazyva mediates B-cell lysis through engagement of immune effector cells, by direct cell death, and by activation of the complement cascade. Due to its reduced fucose content, Gazyva exhibits increased antibody-dependent cellular cytotoxicity than Rituxan (rituximab; Roche/Biogen/Chugai/Zenyaku Kogyo) in vitro in human cancer cell lines, and improves survival in xenograft models of diffuse large B-cell lymphoma and mantle cell lymphoma. As opposed to Rituxan, which is a type I anti-CD20 MAb, this third-generation anti-CD20 MAb is a stronger inducer of direct cell death and antibody-dependent cellular cytotoxicity. Type II anti-CD20 MAbs have also demonstrated less dependence on complement-dependent cytotoxicity, which is an immune response that involves a series of proteins known as the complement system. Complement activation by Rituxan has been associated with infusion-related side effects of the drug.

Analyst Outlook
Gazyva (obinutuzumab; Roche/Biogen/Chugai/Nippon Shinyaku) gained approval for the treatment of Rituxan (rituximab; Roche/Biogen/Chugai/Zenyaku Kogyo)-refractory follicular lymphoma (FL) in combination with Treanda (bendamustine; Teva), followed by Gazyva monotherapy, in February 2016. The drug is Roche’s third-generation anti-CD20 monoclonal antibody (MAb), and is positioned as a potential replacement for Rituxan in the FL market. Gazyva will experience greater uptake with an anticipated label expansion into the lucrative first-line treatment setting, but The author believes that the drug’s pricing strategy will be a major determinant for its success. Roche will have to balance the desire to maximize payback on its investment with its need to enhance its market penetration.