Status - U.S. and EU filings expected

Organizations involved:

Genentech, Inc./Roche – Manuf.; R&D; Tech.; USA mark.

Biogen Idec – R&D; Tech.

Hoffmann-La Roche Ltd. – Parent

Cross ref.: See the Rituxan entry, and also other CD20 antibody entries. Ocrelizumab is sometimes referred to as "next-generation Rituxan."

Description: Ocrelizumab is a humanized IgG1 isotype version of murine 2H7 antibody with affinity for CD20 cellular receptors, presumably expressed by Chinese hamster ovary (CHO) cells. It has a molecular mass (weight) of 148 kDa and calculated molecular formula of C6494H9978N1718O2014S46.

Nomenclature: CD20 Mab, human, rDNA [BIO]; ocrelizumab [USAN; INN]; immunoglobulin G1, anti (human CD20 (antigen)) (human mouse monoclonal 2H7 1 chain), disulfide with human mouse monoclonal 2H7 chain, dimer [CAS]; 637334-45-3 [CAS RN]; CD20 monoclonal antibody, humanized, recombinant [SY]; PR070769 [SY].

Biological.: Compared with rituximab, ocrelizumab binds a different but overlapping epitope on the large extracellular part of CD20 and shows a two to fivefold increased ADCC and three to fivefold decreased CDC, which might lessen infusion-related reactions.

Companies.: Ocrelizumab is being commercially developed by Genentech, now fully part of Hoffmann-La Roche, Ltd. and Biogen Idec. Operating profits for Rituxan are originally to be split 70–30 between Roche and Biogen Idec, respectively. For Biogen Idec, the goal has been to get a potentially safer but equally effective drug as Tysabri, which will extend Biogen Idec’s MS franchise.

Presumably, Genentech/Roche will manufacture and market the product worldwide, with Biogen Idec having U.S. and/or other marketing rights, particularly for MS indications:.

In Oct. 2010, the agreement between Roche and Biogen Idec was modified. Roche assumed full responsibility for the further development of ocrelizumab in multiple sclerosis and will fund all the costs going forward. Biogen Idec "will receive tiered, double-digit royalties on U.S. sales that will approximate its current 30% interest in the compound." The companies are already partners on the drug Rituxan, and the sale of ocrelizumab will not impact that current profit-sharing deal.

FDA class: Biologic BLA

Status: In March 2010, trials and development were terminated for rheumatoid arthritis and lupus erythematosus indication. This step followed the occurrence of deaths due to opportunistic infections, and a recommendation of the independent Data and Safety Monitoring Board (DSMB) based on their assessment of the studies in RA. The review detected an infection related safety signal which included serious and opportunistic infections, some of which were fatal. Development for multiple sclerosis and hematologic cancers, non-Hodgkins Lymphoma (NHL) and chronic lymphocytic leukemia (CLL), is ongoing.

Ocrelizumab presumably has orphan status for one or more indications:.

Trials: As of March 2010, with suspension for RA and SLE indicastions, 2,400 patients treated in trials in more than 30 countries had received ocrelizumab in clinical trials.