Ocrelizumab
Ocrelizumab Uses, Dosage, Side Effects, Food Interaction and all others data.
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 . 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 .
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 . In phase 3 clinical trials of patients with PPMS, treatment with ocrelizumab demonstrated lower rates of clinical and MRI progression than placebo .
| Trade Name | Ocrelizumab |
| Availability | Prescription only |
| Generic | Ocrelizumab |
| Ocrelizumab Other Names | Ocrelizumab, Ocrelizumab (genetical recombination) |
| Related Drugs | Ocrevus, Aubagio, Zeposia, Mavenclad, Gilenya, Tysabri, Vumerity, Copaxone, Tecfidera, Avonex |
| Weight | 300mg/10ml, |
| Type | Intravenous Solution, Intravenous |
| Formula | C6494H9978N1718O2014S46 |
| Weight | 145000.0 Da (Approximate, glycosylated) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ocrelizumab is a CD20 specific monoclonal antibody used to treat relapsing remitting multiple sclerosis.
Indicated for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis .
Ocrelizumab is also used to associated treatment for these conditions: Multiple Sclerosis, Primary Progressive, Relapsing Multiple Sclerosis (RMS)
How Ocrelizumab works
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 . 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 .
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 , 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 . Another mechanism is apoptosis, which may result from cross-linking membrane CD20 on the target cell surface .
Toxicity
Studies assessing the carcinogenicity and mutagenicity of ocrelizumab have not been conducted .
Food Interaction
No interactions found.Ocrelizumab Drug Interaction
Major: teriflunomideModerate: ofatumumab, dimethyl fumarateUnknown: zolpidem, interferon beta-1b, multivitamin with minerals, glatiramer, duloxetine, fentanyl, omega-3 polyunsaturated fatty acids, fluticasone nasal, fluticasone, clonazepam, lamotrigine, escitalopram, acetaminophen, modafinil, cyanocobalamin, cholecalciferol, menaquinone
Ocrelizumab Disease Interaction
Major: hepatitis BModerate: breast cancer, infections, vaccination
Volume of Distribution
Central volume of distribution was 2.78 L .
Elimination Route
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 .
Half Life
The terminal elimination half-life was 26 days .
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 .
Innovators Monograph
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