Sarilumab: First Global Approval
Sarilumab (Kevzara™) is a fully human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin (IL)-6 receptors (sIL-6Rα and mIL-6Rα) and thereby inhibits IL-6-mediated signalling through these receptors. Subcutaneous sarilumab is approved in Canada for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more biological or non-biological disease-modifying anti-rheumatic drugs. It is under regulatory review for use in rheumatoid arthritis in other countries, including in the EU, USA and Japan. Sarilumab is also under phase II investigation for the treatment of juvenile idiopathic arthritis. This article summarizes the milestones in the development of sarilumab leading to its first global approval for the treatment of rheumatoid arthritis.
The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. L.J. Scott is a salaried employee of Adis, Springer SBM.
- 1.Sanofi-aventis Canada Inc. Kevzara™ (sarilumab): product monograph (Canada). 2017. http://pdf.hres.ca/dpd_pm/00037766.PDF. Accessed 6 Mar 2017.
- 3.Smolen JS, Aletaha D, McInnes IA. Rheumatoid arthritis. Lancet. 2016;388:23–38.Google Scholar
- 4.Sanofi, Regeneron Pharmaceuticals. Sanofi and Regeneron announce EMA acceptance for review of Marketing Authorisation Application for sarilumab. 2016. http://www.sanofi.com. Accessed 15 Feb 2017.
- 5.Sanofi, Regeneron Pharmaceuticals Inc. Sanofi and Regeneron announce first approval of KevzaraTM (sarilumab) for the treatment of moderately to severely active rheumatoid arthritis in adult patients by Health Canada. 2017. http://www.sanofi-aventis.com. Accessed 1 Feb 2017.
- 6.Regeneron Pharmaceuticals. Regeneron report third quarter 2016 financial and operating results. Media release. 2016. http://newsroom.regeneron.com/. Accessed 1 Feb 2017.
- 7.Sanofi, Regeneron Pharmaceuticals. Juvenile idiopathic arthritis: NCT02776735 and NCT02991469. 2017. http://clinicaltrials.gov. Accessed 15 Feb 2017.
- 8.Sanofi, Regeneron Pharmaceuticals. Ankylosing spondylitis: NCT01118728 and NCT01061723. 2017. http://clinicaltrials.gov/. Accessed 15 Feb 2017.
- 9.Mangan EK, Parrino J, Wu R, et al. Pharmacodynamic effect and safety of single-dose administration of subcutaneous sarilumab or intravenous tocilizumab in patients with rheumatoid arthritis [abstract no. APL16-0768]. Int J Rheum Dis. 2016;19(Suppl 2):196.Google Scholar
- 10.Boyapati A, Msihid J, Fiore S, et al. Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY. Arthritis Res Ther. 2016;18(1):225.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Huizinga TW, Fleischmann RM, Jasson M, et al. Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73:1626–34.CrossRefPubMedGoogle Scholar
- 14.van der Heijde D, Fan C, van Hoogstraten H, et al. Consistency of radiographic responses with sarilumab plus methotrexate across subpopulations of patients with rheumatoid arthritis in a phase 3 study [abstract no. SAT0058]. Ann Rheum Dis. 2016;75(Suppl 2):685.Google Scholar
- 16.Strand V, Chen C, Mahajan P, et al. Early onset of benefit by patient-reported outcomes (PROs) with sarilumab treatment in RA [abstract no. AB0251]. Ann Rheum Dis. 2016;75(Suppl 2):984–5.Google Scholar
- 18.Strand V, Mahajan P, Chen C, et al. Benefit of sarilumab with csDMARDs on patient productivity in work, household work and family, social, leisure activities in TNF-IR RA patients [abstract no. AB0252]. Ann Rheum Dis. 2016;75(Suppl 2):985.Google Scholar
- 19.Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2016-210310.Google Scholar
- 20.Genovese MC, Fay J, Parrino J, et al. Sarilumab dose reduction to manage laboratory abnormalities in an open-label extension study in RA patients [abstract no. FRI0228]. Ann Rheum Dis. 2016;75(Suppl 2):515–6.Google Scholar
- 21.Fleischmann R, Genovese MC, van Adelsberg J, et al. Pooled safety and efficacy of sarilumab in rheumatoid arthritis patients 65 years of age and older [abstract no. 1605]. Arthritis Rheumatol. 2016;68(Suppl 10).Google Scholar
- 22.Sanofi, Regeneron Pharmaceuticals. Non-infectious uveitis: NCT01900431. 2017. http://clinicaltrials.gov/. Accessed 15 Feb 2017.