Inebilizumab

Last updated

Inebilizumab
Monoclonal antibody
Type Whole antibody
Source Humanized
Target CD19
Clinical data
Pronunciation /ɪˌnɛbɪˈlɪzjʊmæb/
ih-NEH-bih-LIZ-yuum-ab
Trade names Uplizna
Other namesMEDI-551, inebilizumab-cdon
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • None
UNII
KEGG
Chemical and physical data
Formula C6504H10080N1732O2044S44
Molar mass 146652.90 g·mol−1

Inebilizumab, sold under the brand name Uplizna, is a medication for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults. [8] [9] [5] Inebilizumab is a humanized mAb that binds to and depletes CD19+ B cells including plasmablasts and plasma cells. [5]

Contents

The most common adverse reactions include urinary tract infection, headache, joint pain (arthralgia), nausea and back pain. [8] [5]

Inebilizumab was approved for medical use in the United States in June 2020, [8] [10] in the European Union in April 2022, [7] and in Canada in December 2023. [1] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [11]

Medical uses

Inebilizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with a particular antibody (patients who are anti-aquaporin-4 or AQP4 antibody positive). [8] [5]

Neuromyelitis optica spectrum disorder is a rare autoimmune disorder in which immune system cells and autoantibodies attack and damage the optic nerves and spinal cord. [8] Neuromyelitis optica spectrum disorder can be associated with antibodies that bind to a protein called aquaporin-4 (AQP4). Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the central nervous system. [8] Clinically, the disease is manifested with attacks/relapses that result in neurological impairment such as blindness, paraplegia, sensory loss, bladder dysfunction, and peripheral pain. The disability from each attack is cumulative, making neuromyelitis optica spectrum disorder a chronically debilitating and potentially life-threatening disease. [12]

Side effects

The label for inebilizumab includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection — including progressive multifocal leukoencephalopathy, and potential reactivation of hepatitis B and tuberculosis. [8] [5]

The most common adverse reactions in the neuromyelitis optica spectrum disorder clinical trial were urinary tract infection, headache, joint pain (arthralgia), nausea and back pain. [8]

Women who are pregnant should not take inebilizumab because it may cause harm to a developing fetus or newborn baby. [8] The FDA advises health care professionals to inform females of reproductive age to use effective contraception during treatment with inebilizumab and for six months after the last dose. [8]

Vaccination with live-attenuated or live vaccines is not recommended during treatment and should be administered at least four weeks prior to initiation of inebilizumab. [8]

History

Inebilizumab was created from the research led by Thomas Tedder at Cellective Therapeutics, [13] and development was continued by Viela Bio and MedImmune. [14]

Inebilizumab was approved for medical use in the United States in June 2020. [8] [10]

The effectiveness of inebilizumab for the treatment of NMOSD was demonstrated in a clinical study (NCT02200770) of 230 adult participants that evaluated the efficacy and safety of intravenous inebilizumab. [8] In the trial, 213 of the 230 participants had antibodies against AQP4 (anti-AQP4 antibody positive). [8] [10] During the 197-day study, the risk of an NMOSD relapse in the 161 anti-AQP4 antibody positive participants who were treated with inebilizumab was reduced by 77% when compared to the placebo treatment group. [8] There was no evidence of a benefit in participants who were anti-AQP4 antibody negative. [8] The primary efficacy endpoint was the time to the onset of the first adjudicated relapse on or before study day 197 evaluated by a blinded, independent, adjudication committee, who determined whether the attack met protocol-defined criteria. [10] The trial was conducted at 82 sites in 24 countries (including the United States) in North and South America, Europe, Africa, Asia and Australia. [10]

The U.S. Food and Drug Administration (FDA) granted the application for inebilizumab orphan drug designation and granted approval of Uplizna to Viela Bio. [8]

Society and culture

In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Uplizna, intended for the treatment of adults with neuromyelitis optica spectrum disorders (NMOSD) who are anti-aquaporin 4 immunoglobulin G (AQP4-IgG) seropositive. [15] The applicant for this medicinal product is Viela Bio. [15] Inebilizumab was approved for medical use in the European Union in April 2022. [7] [16]

Names

Inebilizumab is the international nonproprietary name (INN) and the United States Adopted Name (USAN). [17] [18]

Related Research Articles

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion.

Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients.

<span class="mw-page-title-main">Aquaporin-4</span> Protein-coding gene in the species Homo sapiens

Aquaporin-4, also known as AQP-4, is a water channel protein encoded by the AQP4 gene in humans. AQP-4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane. A limited number of aquaporins are found within the central nervous system (CNS): AQP1, 3, 4, 5, 8, 9, and 11, but more exclusive representation of AQP1, 4, and 9 are found in the brain and spinal cord. AQP4 shows the largest presence in the cerebellum and spinal cord grey matter. In the CNS, AQP4 is the most prevalent aquaporin channel, specifically located at the perimicrovessel astrocyte foot processes, glia limitans, and ependyma. In addition, this channel is commonly found facilitating water movement near cerebrospinal fluid and vasculature.

Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica. In people with paroxysmal nocturnal hemoglobinuria, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first medication approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion. It is a humanized monoclonal antibody functioning as a terminal complement inhibitor. It binds to the complement C5 protein and inhibits activation of the complement system, a part of the body's immune system. This binding prevents the breakdown of red blood cells in the bloodstream in people with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand the disease better and in the future may help to find new treatments.

Tanezumab is a monoclonal antibody against nerve growth factor as a treatment for pain via a novel mechanisms different from conventional pain-killer drugs. Tanezumab was discovered and developed by Rinat Neuroscience and was acquired by Pfizer in 2006.

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.

Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.

Anifrolumab, sold under the brand name Saphnelo, is a monoclonal antibody used for the treatment of systemic lupus erythematosus. It binds to the type I interferon receptor, blocking the activity of type I interferons such as interferon-α and interferon-β.

MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.

Eptinezumab, sold under the brand name Vyepti, is a medication used for the preventive treatment of migraine in adults. It is a monoclonal antibody that targets calcitonin gene-related peptides (CGRP) alpha and beta. It is administered by intravenous infusion every 3 months.

Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as an anti-cancer medication for the treatment of endometrial cancer. Dostarlimab is a programmed death receptor-1 (PD-1)–blocking monoclonal antibody.

Satralizumab, sold under the brand name Enspryng, is a humanized monoclonal antibody medication that is used for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease. The drug is being developed by Chugai Pharmaceutical, a subsidiary of Roche.

Anti-AQP4 diseases, are a group of diseases characterized by auto-antibodies against aquaporin 4.

Efgartigimod alfa, sold under the brand name Vyvgart, is a medication used to treat myasthenia gravis. Efgartigimod alfa is a neonatal Fc receptor blocker and is a new class of medication. It is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood. The medication causes a reduction in overall levels of IgG, including the abnormal acetylcholine receptor (AChR) antibodies that are present in myasthenia gravis. It is also available coformulated with hyaluronidase.

Teclistamab, sold under the brand name Tecvayli, is a human bispecific monoclonal antibody used for the treatment of relapsed and refractory multiple myeloma. It is a bispecific antibody that targets the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells.

Talquetamab, sold under the brand name Talvey, is a humanized monoclonal antibody used for the treatment of multiple myeloma. It is a bispecific GPRC5D-directed CD3 T-cell engager. Talquetamab is a bispecific antibody against two targets: human CD3, a T-cell surface antigen, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen with potential antineoplastic activity. Talquetamab binds both targets, drawing the T cells close to the tumor cells, causing a cytotoxic T-lymphocyte response. It is being developed by Janssen Pharmaceuticals.

Brenda Banwell is Chief of the Division of Neurology and Co-Director of the Neuroscience Center, and Professor of Neurology at Children's Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. She also holds the title of Professor of Pediatrics and Neurology at the Perelman School of Medicine at the University of Pennsylvania.

References

  1. 1 2 "Uplizna Product information". Health Canada . 22 October 2009. Retrieved 3 March 2024.
  2. ↑ "Summary Basis of Decision for Uplizna". Health Canada . 24 July 2024. Retrieved 12 October 2024.
  3. ↑ "Details for: Uplizna". Health Canada . 15 December 2023. Retrieved 3 March 2024.
  4. ↑ "Regulatory Decision Summary for Uplizna". Drug and Health Products Portal. 15 December 2023. Retrieved 2 April 2024.
  5. 1 2 3 4 5 6 "Uplizna- inebilizumab injection". DailyMed. 8 July 2019. Retrieved 13 June 2020.
  6. ↑ "Uplizna- inebilizumab injection". DailyMed. 27 July 2021. Retrieved 3 March 2023.
  7. 1 2 3 "Uplizna EPAR". European Medicines Agency. 11 November 2021. Retrieved 4 March 2023.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 "FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord". U.S. Food and Drug Administration (FDA) (Press release). 11 June 2020. Retrieved 12 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ "Viela Bio Announces U.S. FDA Approval of Uplizna (inebilizumab-cdon) for the Treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD)". Viela Bio (Press release). 11 June 2020. Retrieved 12 June 2020– via GlobeNewswire.
  10. 1 2 3 4 5 "Drug Trials Snapshots: Uplizna". U.S. Food and Drug Administration (FDA). 11 June 2010. Retrieved 24 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. ↑ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. ↑ "Portfolio". Viela Bio. Archived from the original on 15 November 2018. Retrieved 14 November 2018.
  13. ↑ "Uplizna launch is a 'testament' to NC's prowess in drug R&D | WRAL TechWire". 1 July 2020. Retrieved 8 July 2020.
  14. ↑ "Viela Bio Spins Out of MedImmune". Viela Bio. 28 February 2018. Archived from the original on 27 June 2020. Retrieved 24 June 2020.
  15. 1 2 "Uplizna: Pending EC decision". European Medicines Agency. 11 November 2021. Archived from the original on 12 November 2021. Retrieved 13 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  16. ↑ "Uplizna Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  17. ↑ World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1). hdl: 10665/331046 . License: CC BY-NC-SA 3.0 IGO.
  18. ↑ "Inebilizumab" (PDF). USAN.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.