Identification
- Summary
Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis.
- Brand Names
- Ocrevus
- Generic Name
- Ocrelizumab
- DrugBank Accession Number
- DB11988
- Background
Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of patients with relapsing or primary progressive forms of multiple sclerosis. It is a second-generation recombinant humanized monoclonal IgG1 antibody that selectively targets the B lymphocytes that express the CD20 antigen. As a humanized molecule, ocrelizumab is expected to be less immunogenic with repeated infusions which improves the benefit-to-risk profile for patients with relapsing or progressive forms of MS.
Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system that leads to neurological disabilities and significantly reduced quality of life 5. Most patients with MS experience episodes of relapses with worsening function, followed by recovery periods, or remissions. Primary progressive multiple sclerosis (PPMS) accounts for 10-15% of the overall population of patients with MS, and involves gradual worsening of neurologic disability from symptom onset, often without early relapses or remissions 4.
Developed by Genentech/Roche, ocrelizumab was approved by the FDA in March 2017 under the market name Ocrevustm for intravenous injection. It was later approved by Health Canada (as Ocrevus) in August 2017, making the drug the first available treatment for PPMS in both U.S. and Canada. In clinical trials of patients with relapsing forms of MS, treatment with ocrelizumab resulted in reduced relapse rates and reduced worsening of disability compared to interferon beta-1a 5. In phase 3 clinical trials of patients with PPMS, treatment with ocrelizumab demonstrated lower rates of clinical and MRI progression than placebo 4.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6494H9978N1718O2014S46
- Protein Average Weight
- 145000.0 Da (Approximate, glycosylated)
- Sequences
- Not Available
- Synonyms
- Ocrelizumab
- Ocrelizumab (genetical recombination)
- External IDs
- PR-070769
- PR070769
- R-1594
- RG-1594
Pharmacology
- Indication
Indicated for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis Label.
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- Pharmacodynamics
Since ocrelizumab interferes with the CD20 assay, CD19+B-cells were used to assess B-cell counts after ocrelizumab treatment. 14 days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose to above the lower limit of normal (LLN) or above baseline counts between infusions of ocrelizumab at least one time in 0.3% to 4.1% of patients. In a clinical study involving 51 patients, the time for B-cell counts to return to baseline or LLN was ranged from 27 to 125 weeks, with the median time of 72 weeks, after the last infusion. Within 2.5 years after the last infusion, B-cell counts returned to either baseline or LNN in 90% of the patients Label.
- Mechanism of action
B lymphocytes are known to contribute to the pathogenesis of MS through activation of pro-inflammatory T cells and secretion of proinflammatory cytokines. B cells may differentiate into plasma cells that can produce autoantibodies directed against myelin and cause complement-mediated attack on the myelin sheath 3. CD20 is a cell-surface antigen found on pre-B cells, naïve and mature B cells and memory B cells. However, this activated glycosylated phosphoprotein is not expressed on haematopoietic stem cells, pro-B cells (precursors), or differentiated plasma cells 3,4.
While the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several different proposed mechanisms. Upon cell surface binding to CD20-expressing B lymphocytes, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The capacity for B-cell reconstitution and preexisting humoral immunity is preserved 4, such as levels of IgG and IgM antibodies in the blood of cerebrospinal fluid. Ocrelizumab may induce antibody-dependant cellular cytotoxicity involving macrophages, natural killer cells, and cytotoxic T cells that act together to cause cell death 3. Another mechanism is apoptosis, which may result from cross-linking membrane CD20 on the target cell surface 3.
Target Actions Organism AB-lymphocyte antigen CD20 antagonistantibodyHumans - Absorption
Ocrelizumab displays a two-compartment pharmacokinetic model with time-dependent clearance. The overall exposure at the steady-state (AUC over the 24 week dosing intervals) of ocrelizumab was 3,510 mcg/mL per day. Following intravenous infusion of maintenance doses of 600 mg every 6 months in relapsing MS patients, the mean peak plasma concentration (Cmax) was 212 mcg/mL. Following intravenous infusion of two 300 mg doses separated by 14 days every 6 months in patients with PPMS, Cmax was reported to be 141 mcg/mL. The pharmacokinetics of ocrelizumab was essentially linear and dose proportional between 400 mg and 2000 mg Label.
- Volume of distribution
Central volume of distribution was 2.78 L Label.
- Protein binding
Not Available
- Metabolism
As with other antibodies, ocrelizumab is expected to undergo nonspecific catabolism and broken into smaller peptides and amino acids Label.
- Route of elimination
Not Available
- Half-life
The terminal elimination half-life was 26 days Label.
- Clearance
Constant clearance was estimated at 0.17 L/day, and initial time-dependent clearance at 0.05 L/day. Peripheral volume and inter-compartment clearance were estimated at 2.68 L and 0.29 L/day, respectively Label.
- Adverse Effects
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- Toxicity
Studies assessing the carcinogenicity and mutagenicity of ocrelizumab have not been conducted Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept Ocrelizumab may increase the immunosuppressive activities of Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Ocrelizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ocrelizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Ocrelizumab. Aducanumab The risk or severity of adverse effects can be increased when Ocrelizumab is combined with Aducanumab. Aldesleukin Ocrelizumab may increase the immunosuppressive activities of Aldesleukin. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Ocrelizumab. Alemtuzumab Ocrelizumab may increase the immunosuppressive activities of Alemtuzumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Ocrelizumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Ocrelizumab. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ocrevus Injection, solution, concentrate 300 mg Intravenous Roche Registration Gmb H 2020-12-16 Not applicable EU Ocrevus Injection 300 mg/10mL Intravenous Genentech, Inc. 2017-03-28 Not applicable US Ocrevus Injection, solution, concentrate 300 mg Intravenous Roche Registration Gmb H 2020-12-16 Not applicable EU Ocrevus Solution 30 mg / mL Intravenous Hoffmann La Roche 2017-09-21 Not applicable Canada
Categories
- ATC Codes
- L04AA36 — Ocrelizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- CD20-directed Antibody Interactions
- CD20-directed Cytolytic Antibody
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunomodulatory Agents
- Immunoproteins
- Immunosuppressive Agents
- Proteins
- Selective Immunosuppressants
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- A10SJL62JY
- CAS number
- 637334-45-3
References
- General References
- McGinley MP, Moss BP, Cohen JA: Safety of monoclonal antibodies for the treatment of multiple sclerosis. Expert Opin Drug Saf. 2017 Jan;16(1):89-100. Epub 2016 Oct 31. [Article]
- Reddy V, Dahal LN, Cragg MS, Leandro M: Optimising B-cell depletion in autoimmune disease: is obinutuzumab the answer? Drug Discov Today. 2016 Aug;21(8):1330-8. doi: 10.1016/j.drudis.2016.06.009. Epub 2016 Jun 22. [Article]
- Sorensen PS, Blinkenberg M: The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord. 2016 Jan;9(1):44-52. doi: 10.1177/1756285615601933. [Article]
- Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS: Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21. [Article]
- FDA Press Announcements: FDA approves new drug to treat multiple sclerosis [Link]
- External Links
- KEGG Drug
- D05218
- PubChem Substance
- 347911266
- 1876366
- Wikipedia
- Ocrelizumab
- FDA label
- Download (249 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Multiple Sclerosis 1 4 Active Not Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Completed Treatment Multiple Sclerosis 1 4 Not Yet Recruiting Treatment Multiple Sclerosis 1 4 Recruiting Basic Science Clinically Isolated Syndrome (CIS) / Relapsing Multiple Sclerosis (RMS) 1 4 Recruiting Other Clinically Isolated Syndrome (CIS) / Multiple Sclerosis 2 4 Recruiting Prevention Multiple Sclerosis / Radiologically Isolated Syndrome (RIS) 1 4 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Recruiting Treatment Multiple Sclerosis 2 4 Recruiting Treatment Relapsing Multiple Sclerosis (RMS) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 300 mg/10mL Injection, solution, concentrate Intravenous 300 mg Injection, solution, concentrate Intravenous; Parenteral 300 MG Solution Intravenous 30 mg / mL Injection Parenteral Solution, concentrate Intravenous 30 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAntibody
- General Function
- Mhc class ii protein complex binding
- Specific Function
- This protein may be involved in the regulation of B-cell activation and proliferation.
- Gene Name
- MS4A1
- Uniprot ID
- P11836
- Uniprot Name
- B-lymphocyte antigen CD20
- Molecular Weight
- 33076.99 Da
References
- McGinley MP, Moss BP, Cohen JA: Safety of monoclonal antibodies for the treatment of multiple sclerosis. Expert Opin Drug Saf. 2017 Jan;16(1):89-100. Epub 2016 Oct 31. [Article]
- Reddy V, Dahal LN, Cragg MS, Leandro M: Optimising B-cell depletion in autoimmune disease: is obinutuzumab the answer? Drug Discov Today. 2016 Aug;21(8):1330-8. doi: 10.1016/j.drudis.2016.06.009. Epub 2016 Jun 22. [Article]
Drug created at October 20, 2016 21:08 / Updated at May 21, 2022 00:27