Canakinumab

Canakinumab
Ribbon diagram of canakinumab (blue) bound to IL-1β (yellow) from PDB entry 5bvp[1]
Monoclonal antibody
Type Whole antibody
Source Human
Target IL-1β
Clinical data
Trade names Ilaris
AHFS/Drugs.com Consumer Drug Information
License data
Routes of
administration		 intravenous, subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
ChEMBL
Chemical and physical data
Formula C6452H9958N1722O2010S42
Molar mass 145.2 kg/mol
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Canakinumab (INN, trade name Ilaris, previously ACZ885)[2] is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.[3]

Canakinumab was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the U.S. Food and Drug Administration (FDA) in June 2009[4] and by the European Medicines Agency in October 2009.[5] CAPS is a spectrum of autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disease. In September 2016, FDA approved the use of canakinumab on 3 additional rare and serious auto-inflammatory diseases:[6] Tumor necrosis factor receptor associated periodic syndrome (TRAPS), Hyperimmunoglobulin D syndrome (HIDS)/Mevalonate kinase deficiency (MKD) and Familial Mediterranean fever (FMF).

Canakinumab was being developed by Novartis for the treatment of rheumatoid arthritis, but this trial was completed in October 2009.[7] Canakinumab is also in phase I clinical trials as a possible treatment for chronic obstructive pulmonary disease,[8] gout and coronary artery disease (the CANTOS trial;[9]). It is also in trials for schizophrenia.[10] In gout it may result in better outcomes than a low dose of a steroid but costs five thousand times more.[11]

On Aug 27, 2017, the results of the CANTOS trial were announced at the European Society of Cardiology and published Lancet and the New England Journal of Medicine.[12] CANTOS saw a 15% reduction in deaths from heart attacks, stroke and cardiovascular disease combined. CANTOS also observed serious side-effects, and no statistically significant overall survival benefit. Nonetheless, David Goff, director of the division of cardiovascular sciences at the National Heart, Lung and Blood Institute feels the "public health impact potential is really substantial,” and estimates that in the United States 3 million people might benefit from canakinumab.[12] Further analysis on data from the CANTOS trial also showed a significant reduction in lung cancer incidence and mortality in the canakinumab treated group compared to placebo.

References

  1. ↑ Rondeau JM, Ramage P, Zurini M, Gram H (2015). "The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1β". MAbs. 7 (6): 1151–60. doi:10.1080/19420862.2015.1081323. PMC 4966334. PMID 26284424.
  2. ↑ Dhimolea, Eugen (2010). "Canakinumab". MAbs. 2 (1): 3–13. doi:10.4161/mabs.2.1.10328. PMC 2828573. PMID 20065636.
  3. ↑ Lachmann, HJ; Kone-Paut I; Kuemmerle-Deschner JB; et al. (4 June 2009). "Use of canakinumab in the cryopyrin-associated periodic syndrome". N Engl J Med. 360 (23): 2416–25. doi:10.1056/NEJMoa0810787. PMID 19494217.
  4. ↑ "New biological therapy Ilaris approved in US to treat children and adults with CAPS, a serious life-long auto-inflammatory disease" (Press release). Novartis. 18 June 2009. Retrieved 28 July 2009.
  5. ↑ Wan, Yuet (29 October 2009). "Canakinumab (Ilaris) and rilonacept (Arcalyst) approved in EU for treatment of cryopyrin-associated periodic syndrome". National electronic Library for Medicines. Retrieved 14 April 2010.
  6. ↑ "FDA approves expanded indications for Ilaris for three rare diseases". FDA News Release. 23 September 2016.
  7. ↑ "clinicaltrials.gov, Identifier NCT00784628: Safety, Tolerability and Efficacy of ACZ885 (Canakinumab) in Patients With Active Rheumatoid Arthritis". Retrieved 2010-08-21.
  8. ↑ Yasothan U, Kar S (2008). "Therapies for COPD". Nat Rev Drug Discov. 7 (4): 285. doi:10.1038/nrd2533.
  9. ↑ "CANTOS Summary". theCANTOS.org.
  10. ↑
  11. ↑ Sivera, F; Wechalekar, MD; Andrés, M; Buchbinder, R; Carmona, L (Sep 1, 2014). "Interleukin-1 inhibitors for acute gout". The Cochrane Database of Systematic Reviews. 9: CD009993. doi:10.1002/14651858.CD009993.pub2. PMID 25177840.
  12. 1 2 Johnson, Carolyn (27 August 2017). "Major drug study opens up vast new opportunities in combating heart disease". The Washington Post.
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