Ocrelizumab
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Identification
- Summary
Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis.
- Brand Names
- Ocrevus, Ocrevus Zunovo
- Generic Name
- Ocrelizumab
- DrugBank Accession Number
- DB11988
- Background
Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of patients with primary progressive or relapsing forms of multiple sclerosis (MS).9 It is a second-generation recombinant humanized monoclonal IgG1 antibody that selectively targets B-cells that express the CD20 antigen.2 Compared to non-humanized CD20 antibodies such as rituximab, ocrelizumab is expected to be less immunogenic with repeated infusions, improving the benefit-to-risk profile for patients with MS.1,7
MS is a chronic, inflammatory, autoimmune disease of the central nervous system that leads to neurological disabilities and a significantly reduced quality of life.8 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 leads to the gradual worsening of neurologic disability from symptom onset, often without early relapses or remissions 3.
Developed by Genentech/Roche, ocrelizumab was approved by the FDA in March 2017 under the market name Ocrevus for intravenous injection. It was later approved by Health Canada in August 2017, making the drug the first available treatment for PPMS in both the US 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.8 In phase 3 clinical trials of patients with PPMS, treatment with ocrelizumab led to lower clinical and MRI progression rates compared to placebo.3
- 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
>CDR L1 sequence (SEQ ID 1) RASSSVSYMH
>CDR L2 sequence (SEQ ID 2) APSNLAS
>CDR L3 sequence (SEQ ID 3) QQWSFNPPT
>CDR H1 sequence (SEQ ID 4) GYTFTSYNMH
>CDR H2 sequence (SEQ ID 5) AIYPGNGDTSYNQKFKG
>CDR H3 sequence (SEQ ID 6) VVYYSNSYWYFDV
>Variable light chain sequence (SEQ ID 7) DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKR
>Variable heavy chain sequence (SEQ ID 8) EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV SS
>Light chain amino acid sequence (SEQ ID 9) DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Heavy chain amino acid sequence (SEQ ID 10) EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Heavy chain amino acid sequence (SEQ ID 11) EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Download FASTA FormatReferences:
- Manfrini, M. (2022). Methods for treating multiple sclerosis with ocrelizumab (U.S. Patent No. US 2022/0064320 A1). U.S. Patent and Trademark Office. [Link]
- Synonyms
- Ocrelizumab
- Ocrelizumab (genetical recombination)
- rhuMAb 2H7
- External IDs
- PR-070769
- PR070769
- R-1594
- RG-1594
- RO4964913
Pharmacology
- Indication
Ocrelizumab is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Ocrelizumab is also indicated for the treatment of primary progressive MS in adults.9
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Clinically isolated syndrome (cis) •••••••••••• ••••• ••••••••• Management of Primary progressive multiple sclerosis •••••••••••• ••••• ••••••••• Management of Relapsing multiple sclerosis •••••••••••• ••••• ••••••••• Management of Relapsing remitting multiple sclerosis (rrms) •••••••••••• ••••• ••••••••• Management of Active secondary progressive multiple sclerosis (spms) •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Since ocrelizumab interferes with the CD20 assay, CD19+B-cells are used to assess B-cell counts after treatment. Fourteen days following infusion, a reduction in CD19+B-cell counts was observed. In clinical studies, B-cell counts rose above the lower limit of normal (LLN) or baseline counts between infusions of ocrelizumab at least once 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 ranged from 27 to 125 weeks, with a 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 patients treated with ocrelizumab.9
Since ocrelizumab is a recombinant humanized antibody, it is expected to be less immunogenic than rituximab, a chimeric antibody. Compared to the ocrelizumab pivotal trial, a rituximab phase II trial had a higher proportion of anti-drug antibodies, suggesting greater immunogenicity. However, caution should be exercised since these studies used different assay methods, and the association between anti-drug antibody development and infusion reactions has not been fully elucidated.5 The use of ocrelizumab can cause infusion reactions, and lead to a higher risk of respiratory tract infections and viral infections. Cases of progressive multifocal leukoencephalopathy (PML) and immune-mediated colitis have been reported in patients treated with ocrelizumab. Also, an increased risk of malignancy may exist.9
- Mechanism of action
Ocrelizumab is a recombinant humanized antibody that targets CD20, a glycosylated phosphoprotein expressed on the surface of different types of B-cells. CD20 can be found on pre-B cells, naïve and memory B-cells, and it is not expressed on hematopoietic stem B-cells, pro-B cells (precursors), or differentiated plasma cells.2,3 Therefore, by targeting CD20, ocrelizumab does not affect the concentration of IgG and IgM antibodies in blood or the cerebrospinal fluid.2
B-cells contribute to the pathogenesis of multiple sclerosis (MS) through the activation of proinflammatory T-cells and the secretion of proinflammatory cytokines. Also, B-cells may differentiate into plasma cells that produce autoantibodies directed against myelin, leading to the complement-mediated attack on the myelin sheath 2. By targeting CD20, ocrelizumab specifically depletes B-cells. While the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several proposed mechanisms. It has been suggested that upon cell surface binding to CD20-expressing B-cells, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis while preserving the capacity for B-cell reconstitution and preexisting humoral immunity.2,3,4
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 the intravenous infusion of maintenance doses of 600 mg every 6 months in relapsing MS patients, the mean peak plasma concentration of ocrelizumab (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 141 mcg/mL. Ocrelizumab follows linear and dose proportional pharmacokinetics between 400 mg and 2000 mg.9
- Volume of distribution
In a population pharmacokinetic estimate, the central volume of distribution of ocrelizumab was 2.78 L.9
- Protein binding
Not Available
- Metabolism
As with other antibodies, ocrelizumab is expected to undergo nonspecific catabolism and broken into smaller peptides and amino acids.
- Route of elimination
Monoclonal antibodies (mAb) such as ocrelizumab are too large to be filtered by the kidneys, and therefore, not eliminated in urine under normal conditions. If antibody fragments of low molecular weight are filtered, they are usually reabsorbed and metabolized in the proximal tubule.6 The peptides and amino acids produced by catabolism are recycled or used as an energy source.
- Half-life
The terminal elimination half-life of ocrelizumab was 26 days.9
- Clearance
The constant clearance of ocrelizumab was 0.17 L/day, while the initial time-dependent clearance was 0.05 L/day. Peripheral volume and inter-compartment clearance were 2.68 L and 0.29 L/day, respectively.9
- Adverse Effects
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- Toxicity
Toxicity information regarding ocrelizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as immune-mediated colitis.9 Symptomatic and supportive measures are recommended. The carcinogenic and mutagenic potentials of ocrelizumab have not been evaluated. In monkeys given three loading doses of 15 or 75 mg/kg intravenously, followed by weekly doses of 20 or 100 mg/kg for 8 weeks (2-10 times the recommended human dose), ocrelizumab did not have effects on reproductive organs. No reproductive effects were detected on the estrus cycle of female monkeys given the same ocrelizumab regimen.9
- 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 Ocrelizumab may increase the immunosuppressive activities of Adalimumab. 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. - 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 Solution 30 mg / mL Intravenous Hoffmann La Roche 2017-09-21 Not applicable Canada Ocrevus Injection, solution 920 mg Subcutaneous Roche Registration Gmbh 2024-07-17 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 Gmbh 2020-12-16 Not applicable EU Ocrevus Injection, solution, concentrate 300 mg Intravenous Roche Registration Gmbh 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ocrevus Zunovo Ocrelizumab (920 mg/23mL) + Hyaluronidase (human recombinant) (23000 U/23mL) Injection, solution Subcutaneous Genentech, Inc. 2024-09-13 Not applicable US
Categories
- ATC Codes
- L04AG08 — 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
- Synthesis Reference
Manfrini, M. (2022). Methods for treating multiple sclerosis with ocrelizumab (U.S. Patent No. US 2022/0064320 A1). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/a3/24/be/d30651ed8b7f68/US20220064320A1.pdf
- 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]
- 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]
- Florou D, Katsara M, Feehan J, Dardiotis E, Apostolopoulos V: Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab. Brain Sci. 2020 Oct 20;10(10). pii: brainsci10100758. doi: 10.3390/brainsci10100758. [Article]
- Mancinelli CR, Rossi N, Capra R: Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology. Ther Clin Risk Manag. 2021 Jul 30;17:765-776. doi: 10.2147/TCRM.S282390. eCollection 2021. [Article]
- Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
- Alcala C, Quintanilla-Bordas C, Gascon F, Sempere AP, Navarro L, Carcelen-Gadea M, Landete L, Mallada J, Canizares E, Belenguer A, Carratala S, Dominguez JA, Perez-Miralles FC, Gil-Perotin S, Gasque R, Cubas L, Castillo J, Casanova B: Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study. J Neurol. 2022 Jul;269(7):3676-3681. doi: 10.1007/s00415-022-10989-0. Epub 2022 Feb 2. [Article]
- FDA Press Announcements: FDA approves new drug to treat multiple sclerosis [Link]
- FDA Approved Drug Products: OCREVUS (ocrelizumab) injection for intravenous use [Link]
- FDA Approved Drug Products: OCREVUS® (ocrelizumab) injection, for intravenous use (Jan 2024) [Link]
- External Links
- KEGG Drug
- D05218
- PubChem Substance
- 347911266
- 1876366
- Wikipedia
- Ocrelizumab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Autoimmune Disorder / Demyelinating Disorders / Diseases of the Nervous System / Immune System Diseases / Multiple Sclerosis / Pathologic Processes / Primary Progressive Multiple Sclerosis (PPMS) / Relapsing Remitting Multiple Sclerosis (RRMS) 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Multiple Sclerosis 2 somestatus stop reason just information to hide Not Available Completed Not Available Clinically Isolated Syndrome (CIS) / Multiple Sclerosis 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Multiple Sclerosis 1 somestatus stop reason just information to hide Not Available Completed Not Available Multiple Sclerosis 6 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 300 mg/10mL Injection, solution Subcutaneous 920 mg Injection, solution, concentrate Intravenous 300 mg Injection, solution, concentrate Intravenous; Parenteral 300 MG Solution Intravenous 30 mg / mL Solution Intravenous 300.000 mg Injection, solution, concentrate 300 mg/10ml Injection, solution, concentrate Intravenous 300 mg/10mL Injection, solution Subcutaneous 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
- B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes (PubMed:12920111, PubMed:3925015, PubMed:7684739). Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR (PubMed:12920111, PubMed:18474602, PubMed:7684739)
- Specific Function
- epidermal growth factor receptor binding
- 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]
- Florou D, Katsara M, Feehan J, Dardiotis E, Apostolopoulos V: Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab. Brain Sci. 2020 Oct 20;10(10). pii: brainsci10100758. doi: 10.3390/brainsci10100758. [Article]
- FDA Approved Drug Products: OCREVUS (ocrelizumab) injection for intravenous use [Link]
Drug created at October 20, 2016 21:08 / Updated at January 27, 2024 05:09