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Synonyms: 2H7 | Ocrevus® | PRO70769 | RG1594
ocrelizumab is an approved drug (FDA (2017), EMA (2018))
Compound class: Antibody
Comment: Ocrelizumab is a humanized IgG1 anti-CD20 monoclonal antibody, approved for relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). This is the first therapeutic to gain approval for both of these forms of MS. Ocrelizumab is a modified version of rituximab, developed as a substitute in response to expiration of rituximab patent protection.
The submission documentation for the antibody's INN application contains the peptide sequences for the heavy and light chains of the antibody. BLAST searches of patented peptide sequences reveals identical matches with peptides claimed in patent WO2004056312, which resolve to clones 2H7.v16 and 2H7.v31 .
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.
|Summary of Clinical Use
|The US FDA had granted breakthrough therapy designation for ocrelizumab for the treatment of primary progressive multiple sclerosis which converted to full FDA approval for the treatment of relapsing and primary progressive types of multiple sclerosis in March 2017. Phase 3 clinical trials identified that ocrelizumab produced a pronounced reduction of disease activity in multiple sclerosis patients .
Development of this antibody as a treatment for other inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, and B-cell malignancies has been suspended [3-4].
|Mechanism Of Action and Pharmacodynamic Effects
|Ocrelizumab targets CD20-positive B cells which are implicated in the inflammatory and neurodegenerative processes of multiple sclerosis (MS). By targeting these cells, the aim of this treatment is to be effective whilst leaving immune surveillance intact. A single dose of ocrelizumab has been shown to deplete the subset of highly activated CD3/CD20 positive T cells (that produce substantial quantities of proinflammatory cytokines such as TNFα, IL-1β and IL-17) that were found in all tested MS patients prior to ocrelizumab exposure . Therapeutic efficacy may therefore arise from the combined depletion of CD20 positive B and T cells. Note that rituximab also depletes this pool of T cells in MS patients .
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)