Satralizumab

Last updated
Satralizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target interleukin 6 receptor
Clinical data
Trade names Enspryng
Other namesSA-237, sapelizumab, satralizumab-mwge
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C6340H9776N1684O2022S46
Molar mass 143416.47 g·mol−1

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. [6] [8] The drug is being developed by Chugai Pharmaceutical, a subsidiary of Roche. [9]

Contents

The most common side effects include the common cold (nasopharyngitis), headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea. [6]

Satralizumab regulates inflammation by inhibiting the interleukin-6 (IL-6) receptor, a key mediator of the immune response. [10]

Satralizumab was approved for medical use in the United States in August 2020, [11] and in the European Union in June 2021. [7] [12] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [13]

Medical uses

Satralizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with a particular antibody – people who are anti-aquaporin-4 or AQP4 antibody-positive. [6] [14]

NMOSD is a rare autoimmune disease of the central nervous system that mainly affects the optic nerves and spinal cord. [6] In people with NMOSD, the body's immune system mistakenly attacks healthy cells and proteins in the body, most often those in the optic nerves and spinal cord. [6] Individuals with NMOSD typically have attacks of optic neuritis, which causes eye pain and vision loss. [6] Approximately 50% of people with NMOSD have permanent visual impairment and paralysis caused by NMOSD attacks. [6] Estimates vary, but NMOSD is thought to impact approximately 4,000 to 8,000 Americans. [6]

NMOSD can be associated with antibodies that bind to a protein called aquaporin-4 (AQP4). [6] Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the central nervous system. [6]

Contraindications

Vaccination with live-attenuated or live vaccines is not recommended during treatment and should be administered at least four weeks before starting satralizumab. [6]

Side effects

The most common side effects observed were the common cold (nasopharyngitis), headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea. [6]

The FDA label for satralizumab includes a warning for increased risk of infection, including serious and potentially fatal infections – such as potential reactivation of hepatitis B and tuberculosis. [6] [5] Other warnings and precautions for satralizumab include elevated liver enzymes, decreased neutrophil counts and hypersensitivity reactions. [6]

Pharmacology

Mechanism of action

Satralizumab is a humanized IgG2 monoclonal antibody that binds to soluble and membrane-bound human interleukin-6 (IL-6) receptors and thereby prevents IL-6-mediated signal transmission through these receptors. [10]

IL-6 is a pleiotropic cytokine that is produced by a large number of cell types and is involved in a variety of inflammatory processes. Patients with NMO and NMOSD have elevated levels of IL-6 in cerebro-spinal fluid and serum during periods of active disease. [15] Some of the pro-inflammatory processes involved in NMOSD are thought to involve IL-6, including the formation of pathological autoantibodies against aquaporin-4 (AQP4), and the permeability of the blood-brain barrier to mediators of inflammation. [16] [8]

Efficacy

The effectiveness and safety of satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD) were demonstrated in two 96-week clinical studies. [6] [8] [15] [17] [18]

A study of satralizumab as monotherapy for NMOSD [17] included 95 adult participants, 64 of whom had antibodies against AQP4 (i.e. were anti-AQP4 positive). [6] During this study, treatment with satralizumab reduced the number of NMOSD relapses by 74% in participants who were anti-AQP4 positive compared to treatment with a placebo (inactive treatment). [6]

A study of satralizumab as an adjuvant to immunosuppressant treatment for NMOSD [6] [18] included 76 adult participants; 52 were anti-AQP4 positive. [6] Immunosuppressant treatment in combination with satralizumab reduced the rate of relapses in participants who were anti-AQP4 positive by four-fifths compared to immunosuppressant treatment alone. [6] [18]

The FDA approved satralizumab based on evidence from two clinical trials (Trial 1/ NCT02073279 and Trial 2/NCT02028884) of 116 participants with NMOSD who were anti-aquaporin-4 (AQP4) antibody positive. [14] The trials were conducted at 62 sites in the United States, Canada, Europe and Asia. [14] Participants received at random either satralizumab or placebo injections according to the schedule. [14] Neither the participants nor the healthcare providers knew which treatment was being given. [14] In the second trial, all participants were also receiving their current immunosuppressive medications for the treatment of NMOSD. [14] The benefit of satralizumab was evaluated by measuring the time to the first attack and comparing it to placebo. [14]

There was no evidence of a benefit in participants who were anti-AQP4 antibody negative in either trial. [6]

Society and culture

Satralizumab was approved for the treatment of AQP4-IgG-seropositive NMOSD in Canada, Japan, and Switzerland. [19] [8]

Satralizumab was approved for medical use in the United States in August 2020. [20] [14] [11] The FDA granted the application for satralizumab fast track and orphan drug designations. [6] The FDA granted the approval of Enspryng to Genentech Inc. [6] Satralizumab is the third approved treatment for NMOSD in the United States. [6] The FDA considers satralizumab to be a first-in-class medication. [13]

Satralizumab was approved for medical use in the European Union in June 2021. [7]

Names

Satralizumab is the international nonproprietary name (INN) [21] and the United States Adopted Name (USAN). [22]

Related Research Articles

<span class="mw-page-title-main">Optic neuritis</span> Medical condition

Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.

Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are 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. In more than 80% of cases, NMO is caused by immunoglobulin G autoantibodies to aquaporin 4 (anti-AQP4), the most abundant water channel protein in the central nervous system. A subset of anti-AQP4-negative cases is associated with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG). Rarely, NMO may occur in the context of other autoimmune diseases or infectious diseases. In some cases, the etiology remains unknown.

<span class="mw-page-title-main">Myelin oligodendrocyte glycoprotein</span>

Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.

<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.

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, a severe form of arthritis in children, and COVID‑19. 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.

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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 better the disease and in the future may help to find new treatments.

<span class="mw-page-title-main">Chugai Pharmaceutical Co.</span> Japanese pharmaceutical company

Chugai Pharmaceutical Co., Ltd. is a drug manufacturer operating in Japan. It is a subsidiary controlled by Hoffmann-La Roche, which owns 62% of the company as of 30 June 2014. The company is headquartered in Tokyo. Osamu Nagayama is the current representative director and chairman. Tatsuro Kosaka is the current representative director, president and CEO.

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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.

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

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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 "AusPAR: Satralizumab". Therapeutic Goods Administration (TGA). 23 August 2021. Retrieved 4 September 2021.
  2. 1 2 "Enspryng". Therapeutic Goods Administration (TGA). 26 November 2020. Retrieved 10 September 2021.
  3. ↑ "Satralizumab Product information". Drug Product Database. Health Canada. 25 April 2012. Retrieved 17 August 2020.
  4. ↑ "Summary Basis of Decision (SBD) for Enspryng". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  5. 1 2 "Enspryng- satralizumab injection, solution". DailyMed. 24 August 2020. Retrieved 24 September 2020.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 "FDA Approves Treatment for Rare Disease Affecting Optic Nerves, Spinal Cord". U.S. Food and Drug Administration (FDA). 17 August 2020. Retrieved 17 August 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. 1 2 3 "Enspryng EPAR". European Medicines Agency. 20 April 2021. Retrieved 4 March 2023.
  8. 1 2 3 4 Heo YA (September 2020). "Satralizumab: First Approval". Drugs. 80 (14): 1477–1482. doi: 10.1007/s40265-020-01380-2 . PMC   7522096 . PMID   32797372.
  9. ↑ "Chugai Presents Results from Phase III Study of Satralizumab in NMOSD at ECTRIMS 2018".
  10. 1 2 Rosso M, Saxena S, Chitnis T (May 2020). "Targeting IL-6 receptor in the treatment of neuromyelitis optica spectrum: a review of emerging treatment options". Expert Review of Neurotherapeutics. Informa UK Limited. 20 (5): 509–516. doi:10.1080/14737175.2020.1757434. PMID   32306778. S2CID   216029479.
  11. 1 2 "Drug Approval Package: Enspryng". U.S. Food and Drug Administration (FDA). 11 September 2020. Retrieved 13 September 2020.
  12. ↑ "Enspryng Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  13. 1 2 "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021.
  14. 1 2 3 4 5 6 7 8 "Drug Trials Snapshots: Enspryng". U.S. Food and Drug Administration (FDA). 14 August 2020. Retrieved 13 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. 1 2 "Enspryng". compendium.ch (in German). 2020-07-08. Retrieved 2020-08-10.
  16. ↑ Duchow A, Paul F, Bellmann-Strobl J (September 2020). "Current and emerging biologics for the treatment of neuromyelitis optica spectrum disorders". Expert Opinion on Biological Therapy. Informa UK Limited. 20 (9): 1061–1072. doi:10.1080/14712598.2020.1749259. PMID   32228250. S2CID   214750971.
  17. 1 2 Traboulsee A, Greenberg BM, Bennett JL, Szczechowski L, Fox E, Shkrobot S, et al. (May 2020). "Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial". The Lancet. Neurology. Elsevier BV. 19 (5): 402–412. doi:10.1016/s1474-4422(20)30078-8. PMC   7935419 . PMID   32333898. S2CID   216055515.
  18. 1 2 3 Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, et al. (November 2019). "Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder". The New England Journal of Medicine. Massachusetts Medical Society. 381 (22): 2114–2124. doi: 10.1056/nejmoa1901747 . PMID   31774956.
  19. ↑ "Enspryng (satralizumab)". Roche. Retrieved 9 August 2020.
  20. ↑ "Enspryng: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 17 August 2020.
  21. ↑ World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information. 31 (3): 552. hdl: 10665/330961 . License: CC BY-NC-SA 3.0 IGO.
  22. ↑ "Statement On A Nonproprietary Name Adopted By The USAN Council - Satralizumab]" (PDF). American Medical Association. Archived from the original (PDF) on 2018-09-28. Retrieved 2018-09-28.
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