Siltuximab Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:464390611
Type:mab
Mab Type:mab
Source:xi/o
Target:IL-6
Tradename:Sylvant
Dailymedid:Siltuximab
Atc Prefix:L04
Atc Suffix:AC11
Legal Au:S4
Legal Au Comment:[1]
Legal Us:Rx-only
Legal Us Comment:[2]
Legal Eu:Rx-only
Legal Eu Comment:[3]
Cas Number:541502-14-1
Drugbank:DB09036
Chemspiderid:none
Unii:T4H8FMA7IM
Kegg:D09669
Chembl:1743070
Synonyms:CNTO 328
C:6450
H:9932
N:1688
O:2016
S:50

Siltuximab (INN[4]), sold under the brand name Sylvant, is used for the treatment of people with multicentric Castleman's disease. It is a chimeric (made from human and mouse proteins) monoclonal antibody that binds to interleukin-6. It is an interleukin-6 (IL-6) antagonist.

The common adverse reactions include pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

In April 2014, siltuximab was approved for medical use in the United States for the treatment of people with multicentric Castleman's disease who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8).[5] [6]

Medical uses

Siltuximab is indicated for the treatment of people with multicentric Castleman's disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Side effects

The common adverse reactions include pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

Drug interactions

Siltuximab may increase CYP450 activity leading to increased metabolism of drugs that are CYP450 substrates.

Mechanism of action

Siltuximab is a chimeric monoclonal antibody that binds to interleukin-6 (IL-6), preventing binding to soluble and membrane bound interleukin-6 receptors. Siltuximab interferes with IL-6 mediated growth of B-lymphocytes and plasma cells, secretion of vascular endothelial growth factor (VEGF) and autoimmune phenomena.

History

Siltuximab demonstrated efficacy and safety in people with idiopathic multicentric Castleman disease.[7] [8] Treatment results with siltuximab in B-cell non-Hodgkin's lymphoma are inferior to those obtained in multicentric Castleman disease.[9]

The approval by the US FDA was based on an international, multicenter, randomized (2:1), phase II study comparing every three-week intravenous infusions of siltuximab and best supportive care to placebo and best supportive care. The trial enrolled 79 participants and randomly allocated 53 participants to the siltuximab arm plus best supportive care and 26 participants randomized to the placebo arm plus best supportive care. Siltuximab was administered every three weeks as an intravenous infusion at a dose of 11 mg/kg.

Research

Siltuximab has been investigated for the treatment of neoplastic diseases:[10] metastatic renal cell cancer,[11] prostate cancer,[12] other types of cancer,[13] and for Castleman's disease.[14] [15]

Siltuximab has been evaluated in the treatment of ovarian cancer, however the efficacy for this cancer is debatable.[16] In addition, siltuximab has been evaluated for multiple myeloma, but there was an insignificant increase in response rates.[17]

Notes and References

  1. Web site: Prescription medicines: registration of new chemical entities in Australia, 2015 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 10 April 2023 . 10 April 2023 . https://web.archive.org/web/20230410065829/https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015 . live .
  2. Web site: Sylvant- siltuximab injection, powder, for solution . DailyMed . 21 February 2024 . 8 June 2024.
  3. Web site: Sylvant EPAR . European Medicines Agency . 30 November 2007 . 8 June 2024 . 24 June 2021 . https://web.archive.org/web/20210624074858/https://www.ema.europa.eu/en/medicines/human/EPAR/sylvant . live .
  4. ((World Health Organization)) . 2009 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 62 . WHO Drug Information . 23 . 2 . 10665/74420 . free . World Health Organization .
  5. Web site: Siltuximab . https://web.archive.org/web/20140603005207/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm394675.htm . 3 June 2014 . dead . 23 April 2014 . U.S. Food and Drug Administration (FDA) .
  6. Web site: Sylvant (siltuximab) . accessdata.fda.gov . 28 September 2015 . 8 June 2024 . 8 February 2024 . https://web.archive.org/web/20240208060300/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125496Orig1s000TOC.cfm . live .
  7. David Fajgenbaum . Fajgenbaum DC, Kurzrock R . Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease . Immunotherapy . 8 . 1 . 17–26 . 2016 . 26634298 . 10.2217/imt.15.95 .
  8. Sarosiek S, Shah R, Munshi NC . Review of siltuximab in the treatment of multicentric Castleman's disease . Therapeutic Advances in Hematology . 7 . 6 . 360–366 . December 2016 . 27904739 . 5089324 . 10.1177/2040620716653745 .
  9. Ferrario A, Merli M, Basilico C, Maffioli M, Passamonti F . Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma . Expert Opinion on Investigational Drugs . 26 . 3 . 367–373 . March 2017 . 28140696 . 10.1080/13543784.2017.1288213 . 40363229 .
  10. Korneev KV, Atretkhany KN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SA . TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis . Cytokine . 89 . 127–135 . January 2017 . 26854213 . 10.1016/j.cyto.2016.01.021 .
  11. Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B . A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer . British Journal of Cancer . 103 . 8 . 1154–62 . October 2010 . 20808314 . 2967052 . 10.1038/sj.bjc.6605872 .
  12. Karkera J, Steiner H, Li W, Skradski V, Moser PL, Riethdorf S, Reddy M, Puchalski T, Safer K, Prabhakar U, Pantel K, Qi M, Culig Z . The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study . The Prostate . 71 . 13 . 1455–65 . September 2011 . 21321981 . 10.1002/pros.21362 . 32034042 .
  13. Web site: Siltuximab . ClinicalTrials.gov . 20 October 2011 . 2 July 2019 . https://web.archive.org/web/20190702163437/http://www.clinicaltrials.gov/ct2/results?term=siltuximab . live .
  14. van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H, Sokol L, Crawford J, Cornfeld M, Qi M, Qin X, Herring J, Casper C, Kurzrock R . Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease . Journal of Clinical Oncology . 28 . 23 . 3701–8 . August 2010 . 20625121 . 10.1200/JCO.2009.27.2377 .
  15. Williams SC . First IL-6-blocking drug nears approval for rare blood disorder . Nature Medicine . 19 . 10 . 1193 . October 2013 . 24100967 . 10.1038/nm1013-1193 . 29140516 . free .
  16. Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M . Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities . Current Medicinal Chemistry . 25 . 36 . 4785–4806 . 2018 . 28707587 . 10.2174/0929867324666170712160621 . 30691176 .
  17. Naymagon L, Abdul-Hay M . Novel agents in the treatment of multiple myeloma: a review about the future . Journal of Hematology & Oncology . 9 . 1 . 52 . June 2016 . 27363832 . 4929712 . 10.1186/s13045-016-0282-1 . free .

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