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Ocrelizumab

Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody.[8] It targets CD20 marker on B lymphocytes and is an immunosuppressive drug.[10] Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds.[10]

Ocrelizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetCD20
Clinical data
Trade namesOcrevus
AHFS/Drugs.comMonograph
MedlinePlusa617026
License data
Pregnancy
category
Routes of
administration
Intravenous infusion
ATC code
Legal status
Legal status
Identifiers
CAS Number
  • 637334-45-3 N
DrugBank
  • DB11988 Y
ChemSpider
  • none
UNII
  • A10SJL62JY
KEGG
  • D05218
Chemical and physical data
FormulaC6494H9978N1718O2014S46
Molar mass145818.03 g·mol−1
 NY (what is this?)  (verify)

It was approved by the US Food and Drug Administration (FDA) in March 2017,[11] and the first FDA approved drug for the primary progressive form of MS; it was discovered and developed and is marketed by Hoffmann–La Roche's subsidiary Genentech under the trade name Ocrevus.[12][8] With the approval, the FDA also required the company to conduct several Phase IV clinical trials to better understand whether the drug is safe and effective in young people, cancer risks, and effects on pregnant women and children they might bear.[13]

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[14]

Medical uses edit

In the US, ocrelizumab is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults or for the treatment of primary progressive MS in adults.[8] It is administered by intravenous infusion.[8]

In the EU, ocrelizumab is indicated for the treatment of adults with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features and for the treatment of adults with early primary progressive multiple sclerosis (PPMS) in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity.[9]

Contraindications edit

Ocrelizumab should not be used in people with hepatitis B infection or a history of severe reaction to this drug. If someone has an infection or infectious disease, treatment should be delayed until the infection is resolved. It has not been tested in pregnant women, but based on animal studies does not appear to be safe for pregnant women; it is excreted in breast milk, and effects on infants are unknown.[8]

Adverse effects edit

As of October 2016 the three Phase III clinical trials of ocrelizumab used to obtain approval had not been published. Based on published data from clinical trials at that time, the most common adverse events were infusion reactions including itchy skin, rash, hives, flushing, throat and mouth irritation, fever, fatigue, nausea, rapid heart beating, headache, and dizziness. One person died from a systemic inflammatory response syndrome and in another trial, rates of cancer were three times higher (2.3% vs. 0.8%) in people taking the drug than people taking placebo. Clinical trials in rheumatoid arthritis and lupus were halted because rates of serious infections were too high; these results were not seen in published trials in people with MS, and the differences may be due to the differences in the bodies of people with the different diseases, as well as other drugs they were taking.[10]

There is an increased risk of infections of all kinds, including respiratory infections, in people taking immunosuppressive drugs like ocrelizumab. In clinical trials submitted to the FDA, more people taking ocrelizumab got infections than people taking Interferon beta-1a did, including upper and lower respiratory infections, herpes, and hepatitis B reactivation. The risk of progressive multifocal leukoencephalopathy, a disease caused by viral infection of the brain, is also increased.[8]

An increased risk of malignancy with ocrelizumab may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in ocrelizumab-treated patients. Breast cancer occurred in 6 of 781 females treated with ocrelizumab for MS in clinical trials. None of 668 females treated in Rebif (interferon beta-1a) or placebo arms of the clinical trials developed breast cancer. Patients should follow standard breast cancer screening guidelines.[8]

Pharmacology edit

Ocrelizumab is an immunosuppressive drug; it binds to CD20, which is selectively made and membrane expressed by B cells. When ocrelizumab binds to CD20 on B cells, these cells are deleted by antibody-dependent cell-mediated cytotoxicity and, to a lesser extent, complement-dependent cytotoxicity.[10][15]

Chemistry edit

Ocrelizumab is a humanized monoclonal antibody that binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.[10] It has an immunoglobulin G1 with a variable region against human CD20, with a human-mouse monoclonal 2H7 γ1-chain, bound via disulfide links with human-mouse monoclonal 2H7 κ-chain in a dimer.[16]

History edit

A study of rituximab in MS with strong results, published in The New England Journal of Medicine in 2008, drove interest in B-cell depletion as a strategy to treat MS and has led to extensive off-label use of rituximab to treat primary and relapsing MS.[10][17] Rituximab is a mouse protein, and is immunogenic in humans, and Genentech and its parent Roche decided to focus on the similar, but humanized mAb that they already had, ocrelizumab, for MS instead.[12]

Clinical trials in people with rheumatoid arthritis and lupus were halted in 2010 because people with these conditions developed too many opportunistic infections when taking ocrelizumab.[10][18] It was also studied in hematological cancer.[19]

In MS, phase II results were announced in October 2010, and in October 2015, Genentech presented interim results of three Phase III clinical trials.[20] In February, 2016 the FDA granted Breakthrough Therapy Designation for primary progressive multiple sclerosis.[21]

On March 28, 2017, the FDA approved ocrelizumab for relapsing-remitting and primary-progressive multiple sclerosis. It is the first FDA-approved treatment for the primary progressive form.[22][11] When the FDA approved the drug, it required Roche to conduct several Phase IV clinical trials, including: a two-part study in people between ten and 17 years old with relapsing multiple sclerosis to determine dosing, then safety and efficacy in these people, required to be completed by 2024; a prospective five-year study to better understand the risk of cancer, required to be completed by 2030; a prospective study creating a registry of women with MS exposed to ocrelizumab before and during pregnancy, women with MS not exposed to ocrelizumab, and women without MS, to understand the effect on women and children they might bear, due by 2029; an additional pregnancy outcomes study due by 2024; and an additional non-human primate study on fetal development and outcomes due by 2019.[13]

The efficacy of ocrelizumab for the treatment of relapsing forms of MS was shown in two clinical trials in 1,656 participants treated for 96 weeks.[22][23] Both studies compared ocrelizumab to another MS drug, Rebif (interferon beta-1a).[22] In both studies, the patients receiving ocrelizumab had reduced relapse rates and reduced worsening of disability compared to Rebif.[22][23] The trials were conducted in the US, Canada, Europe, Latin America, Africa, and Australia.[23]

In a study of PPMS in 732 participants treated for at least 120 weeks, those receiving ocrelizumab showed a longer time to the worsening of disability compared to placebo.[22][23] The study was conducted in the US, Canada, and Europe.[23]

The application for ocrelizumab was granted breakthrough therapy, fast track, and priority review designations.[22] The FDA granted approval of Ocrevus to Genentech, Inc.[22]

Ocrelizumab was approved for use in the European Union in January 2018.[9]

References edit

  1. ^ "Ocrelizumab (Ocrevus) Use During Pregnancy". Drugs.com. 13 August 2019. Retrieved 28 March 2020.
  2. ^ a b "Ocrevus PI" (PDF). Retrieved 31 March 2024.
  3. ^ "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
  4. ^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.
  5. ^ "Regulatory Decision Summary for Ocrevus". Drug and Health Product Register. 23 October 2014.
  6. ^ "Neurological therapies". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  7. ^ "Ocrevus 300 mg concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). 30 December 2019. Retrieved 28 March 2020.
  8. ^ a b c d e f g h "Ocrevus- ocrelizumab injection". DailyMed. 13 December 2019. Retrieved 25 April 2020.
  9. ^ a b c "Ocrevus EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 25 April 2020.   This article incorporates text from this source, which is in the public domain.
  10. ^ a b c d e f g McGinley MP, Moss BP, Cohen JA (January 2017). "Safety of monoclonal antibodies for the treatment of multiple sclerosis". Expert Opinion on Drug Safety. 16 (1): 89–100. doi:10.1080/14740338.2017.1250881. PMID 27756172. S2CID 36762194.
  11. ^ a b "Ocrevus (ocrelizumab) Injection". U.S. Food and Drug Administration (FDA). 9 May 2017. Retrieved 25 April 2020.
  12. ^ a b Winslow R (28 March 2017). "After 40-year odyssey, first drug for aggressive MS wins FDA approval". STAT.
  13. ^ a b "BLA Approval Letter" (PDF). U.S. Food and Drug Administration (FDA). 28 March 2017.
  14. ^ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
  15. ^ Reddy V, Dahal LN, Cragg MS, Leandro M (August 2016). "Optimising B-cell depletion in autoimmune disease: is obinutuzumab the answer?" (PDF). Drug Discovery Today. 21 (8): 1330–8. doi:10.1016/j.drudis.2016.06.009. PMID 27343722.
  16. ^ World Health Organization (2006). "International nonproprietary names for pharmaceutical substances (INN) : recommended international nonproprietary names (Rec. INN) : list 56". WHO Drug Information. 20 (3): 220. hdl:10665/73839.
  17. ^ Sorensen PS, Blinkenberg M (January 2016). "The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects". Therapeutic Advances in Neurological Disorders. 9 (1): 44–52. doi:10.1177/1756285615601933. PMC 4710102. PMID 26788130.
  18. ^ Reid K (8 March 2010). "Update 2. Roche suspends arthritis treatment after deaths". Reuters.
  19. ^ Hutas G (November 2008). "Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies". Current Opinion in Investigational Drugs. 9 (11): 1206–15. PMID 18951300.
  20. ^ "First Data From Ocrelizumab Phase 3 Studies in MS. Oct 2015". Medscape Log.
  21. ^ Nather D (19 February 2016). "New drug for severe form of MS generates glimmer of hope". STAT.
  22. ^ a b c d e f g "FDA approves new drug to treat multiple sclerosis". U.S. Food and Drug Administration (FDA) (Press release). 29 March 2017. Retrieved 25 April 2020.   This article incorporates text from this source, which is in the public domain.
  23. ^ a b c d e "Drug Trials Snapshots: Ocrevus". U.S. Food and Drug Administration (FDA). 28 March 2017. Retrieved 25 April 2020.   This article incorporates text from this source, which is in the public domain.

ocrelizumab, confused, with, eculizumab, sold, under, brand, name, ocrevus, medication, used, treatment, multiple, sclerosis, humanized, anti, cd20, monoclonal, antibody, targets, cd20, marker, lymphocytes, immunosuppressive, drug, binds, epitope, that, overla. Not to be confused with eculizumab Ocrelizumab sold under the brand name Ocrevus is a medication used for the treatment of multiple sclerosis MS It is a humanized anti CD20 monoclonal antibody 8 It targets CD20 marker on B lymphocytes and is an immunosuppressive drug 10 Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds 10 OcrelizumabMonoclonal antibodyTypeWhole antibodySourceHumanized from mouse TargetCD20Clinical dataTrade namesOcrevusAHFS Drugs comMonographMedlinePlusa617026License dataUS DailyMed OcrelizumabPregnancycategoryAU C 1 2 Routes ofadministrationIntravenous infusionATC codeL04AG08 WHO Legal statusLegal statusAU S4 Prescription only 2 3 4 CA only Schedule D 5 6 UK POM Prescription only 7 US only 8 EU Rx only 9 In general Prescription only IdentifiersCAS Number637334 45 3 NDrugBankDB11988 YChemSpidernoneUNIIA10SJL62JYKEGGD05218Chemical and physical dataFormulaC 6494H 9978N 1718O 2014S 46Molar mass145818 03 g mol 1 N Y what is this verify It was approved by the US Food and Drug Administration FDA in March 2017 11 and the first FDA approved drug for the primary progressive form of MS it was discovered and developed and is marketed by Hoffmann La Roche s subsidiary Genentech under the trade name Ocrevus 12 8 With the approval the FDA also required the company to conduct several Phase IV clinical trials to better understand whether the drug is safe and effective in young people cancer risks and effects on pregnant women and children they might bear 13 The US Food and Drug Administration FDA considers it to be a first in class medication 14 Contents 1 Medical uses 2 Contraindications 3 Adverse effects 4 Pharmacology 5 Chemistry 6 History 7 ReferencesMedical uses editIn the US ocrelizumab is indicated for the treatment of relapsing forms of multiple sclerosis MS to include clinically isolated syndrome relapsing remitting disease and active secondary progressive disease in adults or for the treatment of primary progressive MS in adults 8 It is administered by intravenous infusion 8 In the EU ocrelizumab is indicated for the treatment of adults with relapsing forms of multiple sclerosis RMS with active disease defined by clinical or imaging features and for the treatment of adults with early primary progressive multiple sclerosis PPMS in terms of disease duration and level of disability and with imaging features characteristic of inflammatory activity 9 Contraindications editOcrelizumab should not be used in people with hepatitis B infection or a history of severe reaction to this drug If someone has an infection or infectious disease treatment should be delayed until the infection is resolved It has not been tested in pregnant women but based on animal studies does not appear to be safe for pregnant women it is excreted in breast milk and effects on infants are unknown 8 Adverse effects editAs of October 2016 the three Phase III clinical trials of ocrelizumab used to obtain approval had not been published Based on published data from clinical trials at that time the most common adverse events were infusion reactions including itchy skin rash hives flushing throat and mouth irritation fever fatigue nausea rapid heart beating headache and dizziness One person died from a systemic inflammatory response syndrome and in another trial rates of cancer were three times higher 2 3 vs 0 8 in people taking the drug than people taking placebo Clinical trials in rheumatoid arthritis and lupus were halted because rates of serious infections were too high these results were not seen in published trials in people with MS and the differences may be due to the differences in the bodies of people with the different diseases as well as other drugs they were taking 10 There is an increased risk of infections of all kinds including respiratory infections in people taking immunosuppressive drugs like ocrelizumab In clinical trials submitted to the FDA more people taking ocrelizumab got infections than people taking Interferon beta 1a did including upper and lower respiratory infections herpes and hepatitis B reactivation The risk of progressive multifocal leukoencephalopathy a disease caused by viral infection of the brain is also increased 8 An increased risk of malignancy with ocrelizumab may exist In controlled trials malignancies including breast cancer occurred more frequently in ocrelizumab treated patients Breast cancer occurred in 6 of 781 females treated with ocrelizumab for MS in clinical trials None of 668 females treated in Rebif interferon beta 1a or placebo arms of the clinical trials developed breast cancer Patients should follow standard breast cancer screening guidelines 8 Pharmacology editOcrelizumab is an immunosuppressive drug it binds to CD20 which is selectively made and membrane expressed by B cells When ocrelizumab binds to CD20 on B cells these cells are deleted by antibody dependent cell mediated cytotoxicity and to a lesser extent complement dependent cytotoxicity 10 15 Chemistry editOcrelizumab is a humanized monoclonal antibody that binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds 10 It has an immunoglobulin G1 with a variable region against human CD20 with a human mouse monoclonal 2H7 g1 chain bound via disulfide links with human mouse monoclonal 2H7 k chain in a dimer 16 History editA study of rituximab in MS with strong results published in The New England Journal of Medicine in 2008 drove interest in B cell depletion as a strategy to treat MS and has led to extensive off label use of rituximab to treat primary and relapsing MS 10 17 Rituximab is a mouse protein and is immunogenic in humans and Genentech and its parent Roche decided to focus on the similar but humanized mAb that they already had ocrelizumab for MS instead 12 Clinical trials in people with rheumatoid arthritis and lupus were halted in 2010 because people with these conditions developed too many opportunistic infections when taking ocrelizumab 10 18 It was also studied in hematological cancer 19 In MS phase II results were announced in October 2010 and in October 2015 Genentech presented interim results of three Phase III clinical trials 20 In February 2016 the FDA granted Breakthrough Therapy Designation for primary progressive multiple sclerosis 21 On March 28 2017 the FDA approved ocrelizumab for relapsing remitting and primary progressive multiple sclerosis It is the first FDA approved treatment for the primary progressive form 22 11 When the FDA approved the drug it required Roche to conduct several Phase IV clinical trials including a two part study in people between ten and 17 years old with relapsing multiple sclerosis to determine dosing then safety and efficacy in these people required to be completed by 2024 a prospective five year study to better understand the risk of cancer required to be completed by 2030 a prospective study creating a registry of women with MS exposed to ocrelizumab before and during pregnancy women with MS not exposed to ocrelizumab and women without MS to understand the effect on women and children they might bear due by 2029 an additional pregnancy outcomes study due by 2024 and an additional non human primate study on fetal development and outcomes due by 2019 13 The efficacy of ocrelizumab for the treatment of relapsing forms of MS was shown in two clinical trials in 1 656 participants treated for 96 weeks 22 23 Both studies compared ocrelizumab to another MS drug Rebif interferon beta 1a 22 In both studies the patients receiving ocrelizumab had reduced relapse rates and reduced worsening of disability compared to Rebif 22 23 The trials were conducted in the US Canada Europe Latin America Africa and Australia 23 In a study of PPMS in 732 participants treated for at least 120 weeks those receiving ocrelizumab showed a longer time to the worsening of disability compared to placebo 22 23 The study was conducted in the US Canada and Europe 23 The application for ocrelizumab was granted breakthrough therapy fast track and priority review designations 22 The FDA granted approval of Ocrevus to Genentech Inc 22 Ocrelizumab was approved for use in the European Union in January 2018 9 References edit Ocrelizumab Ocrevus Use During Pregnancy Drugs com 13 August 2019 Retrieved 28 March 2020 a b Ocrevus PI PDF Retrieved 31 March 2024 Prescription medicines registration of new chemical entities in Australia 2017 Therapeutic Goods Administration TGA 21 June 2022 Retrieved 9 April 2023 Prescription medicines and biologicals TGA annual summary 2017 Therapeutic Goods Administration TGA 21 June 2022 Retrieved 31 March 2024 Regulatory Decision Summary for Ocrevus Drug and Health Product Register 23 October 2014 Neurological therapies Health Canada 9 May 2018 Retrieved 13 April 2024 Ocrevus 300 mg concentrate for solution for infusion Summary of Product Characteristics SmPC emc 30 December 2019 Retrieved 28 March 2020 a b c d e f g h Ocrevus ocrelizumab injection DailyMed 13 December 2019 Retrieved 25 April 2020 a b c Ocrevus EPAR European Medicines Agency EMA 17 September 2018 Retrieved 25 April 2020 nbsp This article incorporates text from this source which is in the public domain a b c d e f g McGinley MP Moss BP Cohen JA January 2017 Safety of monoclonal antibodies for the treatment of multiple sclerosis Expert Opinion on Drug Safety 16 1 89 100 doi 10 1080 14740338 2017 1250881 PMID 27756172 S2CID 36762194 a b Ocrevus ocrelizumab Injection U S Food and Drug Administration FDA 9 May 2017 Retrieved 25 April 2020 a b Winslow R 28 March 2017 After 40 year odyssey first drug for aggressive MS wins FDA approval STAT a b BLA Approval Letter PDF U S Food and Drug Administration FDA 28 March 2017 New Drug Therapy Approvals 2017 PDF U S Food and Drug Administration FDA Report January 2018 Retrieved 16 September 2020 Reddy V Dahal LN Cragg MS Leandro M August 2016 Optimising B cell depletion in autoimmune disease is obinutuzumab the answer PDF Drug Discovery Today 21 8 1330 8 doi 10 1016 j drudis 2016 06 009 PMID 27343722 World Health Organization 2006 International nonproprietary names for pharmaceutical substances INN recommended international nonproprietary names Rec INN list 56 WHO Drug Information 20 3 220 hdl 10665 73839 Sorensen PS Blinkenberg M January 2016 The potential role for ocrelizumab in the treatment of multiple sclerosis current evidence and future prospects Therapeutic Advances in Neurological Disorders 9 1 44 52 doi 10 1177 1756285615601933 PMC 4710102 PMID 26788130 Reid K 8 March 2010 Update 2 Roche suspends arthritis treatment after deaths Reuters Hutas G November 2008 Ocrelizumab a humanized monoclonal antibody against CD20 for inflammatory disorders and B cell malignancies Current Opinion in Investigational Drugs 9 11 1206 15 PMID 18951300 First Data From Ocrelizumab Phase 3 Studies in MS Oct 2015 Medscape Log Nather D 19 February 2016 New drug for severe form of MS generates glimmer of hope STAT a b c d e f g FDA approves new drug to treat multiple sclerosis U S Food and Drug Administration FDA Press release 29 March 2017 Retrieved 25 April 2020 nbsp This article incorporates text from this source which is in the public domain a b c d e Drug Trials Snapshots Ocrevus U S Food and Drug Administration FDA 28 March 2017 Retrieved 25 April 2020 nbsp This article incorporates text from this source which is in the public domain Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Ocrelizumab amp oldid 1219833796, wikipedia, wiki, book, books, library,

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