ocrelizumab

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Ligands
ocrelizumab

GtoPdb Ligand ID: 7580

Synonyms: 2H7 | Ocrevus® | PRO70769 | RG1594

ocrelizumab is an approved drug (FDA (2017), EMA (2018))

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 [1].

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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 [5]. 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].

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 [5].

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 [2]. 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 [6].

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 [2]. 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 [6].