Sutimlimab

Last updated

Sutimlimab
Monoclonal antibody
Type Whole antibody
Source Chimeric/humanized hybrid
Target complement component 1s
Clinical data
Trade names Enjaymo
Other namesBIVV009, sutimlimab-jome
License data
Routes of
administration 		Intravenous infusion
ATC code
Legal status
Legal status
Identifiers
CAS Number
UNII
KEGG

Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). [1] [3] [4] It is given by intravenous infusion. [1] Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro. [5]

Contents

The most common side effects include headache, high blood pressure, urinary tract infection (infection of the structures that carry urine), upper respiratory tract infection (nose and throat infection), nasopharyngitis (inflammation of the nose and throat), nausea, abdominal pain, infusion-related reactions and cyanosis (bluish discoloration of hands and feet in response to cold and stress). [2]

This drug is being developed by Bioverativ, a Sanofi company. [6] Sutimlimab was approved for medical use in the United States in February 2022, [3] [7] and in the European Union in November 2022. [2] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [8]

Medical uses

Sutimlimab is indicated to decrease the need for red blood cell transfusion due to hemolysis (red blood cell destruction) in adults with cold agglutinin disease (CAD). [1] [3]

Adverse effects

The most common side effects include respiratory tract infection, viral infection, diarrhea, dyspepsia (indigestion), cough, arthralgia (joint stiffness), arthritis, and swelling in the lower legs and hands. [3] In two phase 3 studies (n=66), 29% of patients experienced infusion-related reactions, including shortness of breath, rapid heartbeat, nausea, flushing, headache, hypotension, chest discomfort, pruritis, rash, injection site reaction, and dizziness. [9]

Pharmacology

Mechanism of action

Sutimlimab targets the C1s enzyme and inhibits its enzymatic propagation of the classical complement pathway, thereby, preventing the formation of the C3-convertase enzyme. [10]

History

The effectiveness of sutimlimab was assessed in a study of 24 adults with cold agglutinin disease who had a blood transfusion within the past six months. [3] All participants received sutimlimab for up to six months and could choose to continue therapy in a second part of the trial. [3] Based on body weight, participants received either a 6.5 g or 7.5 g infusion of sutimlimab into their vein on day 0, day 7, and every 14 days through week 25. [3]

In total, 54% of participants responded to sutimlimab. [3] The response was defined in the study as an increase in hemoglobin (an indirect measurement of the amount of red blood cells that are not destroyed) of 2 g/dL or greater (or to 12 g/dL or greater), and no red blood cell transfusions after the first five weeks of treatment; and no other therapies for cold agglutinin disease as defined in the study. [3]

The U.S. Food and Drug Administration (FDA) granted the application for sutimlimab orphan drug, [3] [11] breakthrough therapy, [3] and priority review designations. [3]

Society and culture

On 15 September 2022, 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 Enjaymo, intended for the treatment of hemolytic anemia in adults with cold agglutinin disease (CAD). [12] The applicant for this medicinal product is Genzyme Europe BV. [12] Sutimlimab was approved for medical use in the European Union in November 2022. [2] [13]

Names

Sutimlimab is the International nonproprietary name (INN). [14]

Related Research Articles

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C.

Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis, and neuromyelitis optica. In people with PNH, 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 drug approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion.

<span class="mw-page-title-main">Ofatumumab</span>

Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Union and other regions. Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States. It is sold by Novartis under license from Genmab.

<span class="mw-page-title-main">Ruxolitinib</span> Medication

Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.

Betibeglogene autotemcel, sold under the brand name Zynteglo, is a gene therapy for the treatment for beta thalassemia. It was developed by Bluebird Bio and was given breakthrough therapy designation by the US Food and Drug Administration in February 2015.

<span class="mw-page-title-main">Duvelisib</span> PI3K inhibitor

Duvelisib, sold under the brand name Copiktra, is a medication used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed. It is taken by mouth. It is a PI3 kinase inhibitor.

Crizanlizumab, sold under the brand name Adakveo among others, is a monoclonal antibody medication that binds to P-selectin. It is a medication used to reduce the frequency of vaso-occlusive crisis in people aged 16 years and older who have sickle cell anemia. It is given by injection into a vein.

Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes.

<span class="mw-page-title-main">Loncastuximab tesirine</span> Medication

Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.

Ravulizumab, sold under the brand name Ultomiris, is a humanized monoclonal antibody complement inhibitor medication designed for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. It is designed to bind to and prevent the activation of Complement component 5 (C5).

<span class="mw-page-title-main">Voxelotor</span> Medication

Voxelotor, sold under the brand name Oxbryta, is a medication used for the treatment of sickle cell disease. Voxelotor is the first hemoglobin oxygen-affinity modulator. Voxelotor has been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators in sickle cell patients. It has a safe profile in sickle cell patients and healthy volunteers, without any dose-limiting toxicity. It was developed by Global Blood Therapeutics, a subsidiary of Pfizer.

<span class="mw-page-title-main">Trastuzumab deruxtecan</span> Medication

Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.

Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).

Pegcetacoplan, sold under the brand name Empaveli, among others, is a medication used to treat paroxysmal nocturnal hemoglobinuria and geographic atrophy of the retina. Pegcetacoplan is a complement inhibitor.

Amivantamab, sold under the brand name Rybrevant, is a bispecific monoclonal antibody used to treat non-small cell lung cancer. Amivantamab is a bispecific epidermal growth factor (EGF) receptor-directed and mesenchymal–epithelial transition (MET) receptor-directed antibody. It is the first treatment for adults with non-small cell lung cancer whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

Tebentafusp, sold under the brand name Kimmtrak, is an anti-cancer medication used to treat uveal melanoma. Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager. Tebentafusp is given by intravenous infusion.

<span class="mw-page-title-main">Mitapivat</span> Chemical compound

Mitapivat, sold under the brand name Pyrukynd, is a medication used to treat hemolytic anemia. It is taken as the sulfate hydrate salt by mouth. Mitapivat is a pyruvate kinase activator.

Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

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.

References

  1. 1 2 3 4 "Enjaymo- sutimlimab injection, solution, concentrate". DailyMed. 1 February 2022. Archived from the original on 21 February 2022. Retrieved 20 February 2022.
  2. 1 2 3 4 "Enjaymo EPAR". European Medicines Agency (EMA). 14 September 2022. Retrieved 4 March 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves treatment for adults with rare type of anemia". U.S. Food and Drug Administration. 4 February 2022. Archived from the original on 6 February 2022. Retrieved 6 February 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. ↑ Tvedt TH, Steien E, Øvrebø B, Haaverstad R, Hobbs W, Wardęcki M, et al. (February 2022). "Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery". American Journal of Hematology. 97 (2): E51–E54. doi: 10.1002/ajh.26409 . PMID   34778998. S2CID   244116614.
  5. ↑ Nikitin PA, Rose EL, Byun TS, Parry GC, Panicker S (February 2019). "C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro". Journal of Immunology. 202 (4): 1200–1209. doi:10.4049/jimmunol.1800998. PMC   6360260 . PMID   30635392.
  6. ↑ "Sutimlimab FDA Approval Status". FDA. 19 May 2020. Archived from the original on 31 December 2021. Retrieved 31 December 2021.
  7. ↑ "FDA approves Enjaymo (sutimlimab-jome), first treatment for use in patients with cold agglutinin disease". Sanofi (Press release). 4 February 2022. Archived from the original on 5 February 2022. Retrieved 6 February 2022.
  8. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Retrieved 22 January 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ FDA Professional Drug Information
  10. ↑ Bartko J, Schoergenhofer C, Schwameis M, Firbas C, Beliveau M, Chang C, et al. (October 2018). "A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway". Clinical Pharmacology and Therapeutics. 104 (4): 655–663. doi:10.1002/cpt.1111. PMC   6175298 . PMID   29737533.
  11. ↑ "Sutimlimab Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 27 July 2016. Archived from the original on 7 February 2022. Retrieved 6 February 2022.
  12. 1 2 "Enjaymo: Pending EC decision". European Medicines Agency (EMA). 15 September 2022. Archived from the original on 16 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ↑ "Enjaymo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  14. ↑ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl: 10665/330907 .
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.