BioDrugs

, Volume 28, Issue 3, pp 313–321 | Cite as

A Review of CT-P13: An Infliximab Biosimilar

Adis Drug Evaluation

Abstract

CT-P13 (Remsima™; Inflectra™), a biosimilar of reference infliximab (Remicade®), is approved by the European Medicines Agency for use in all indications for which reference infliximab is approved, including rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriatic arthritis and psoriasis. Infliximab is a chimeric human-murine monoclonal antibody against the proinflammatory cytokine tumour necrosis factor-α. The CT-P13 infliximab formulation is identical to that of reference infliximab and it has similar physiochemical characteristics. The approval of CT-P13 was based on the results of a rigorous, comparability exercise. This article reviews the results of that exercise, focusing on the clinical evaluation programme. In two well-designed clinical trials, CT-P13 was equivalent to reference infliximab in terms of pharmacokinetic properties in patients with ankylosing spondylitis and in terms of efficacy in patients with rheumatoid arthritis. In both studies, CT-P13 was generally well tolerated with a similar tolerability profile to that of reference infliximab. Immunogenicity evaluations demonstrated that the proportion of patients developing anti-drug antibodies was similar with each agent. Preliminary data from trial extensions demonstrated that in patients who switched from reference infliximab to CT-P13, efficacy was sustained and similar to those who were treated continuously with CT-P13. As with all biosimilar and generic agents, CT-P13 has the potential to reduce treatment costs compared with those of reference infliximab, and modelled analyses predict significant cost savings compared with reference infliximab. In conclusion, CT-P13 is an infliximab biosimilar that provides a useful alternative to reference infliximab in patients requiring infliximab therapy.

Notes

Disclosure

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 this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

References

  1. 1.
    World Health Organization. Guidelines on evaluation of similar biotherapeutic products (SBPs); 2009. http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf. Accessed 19 Dec 2013.
  2. 2.
    European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. Draft; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/06/WC500144124.pdf. Accessed 17 Feb 2014.
  3. 3.
    European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Assessment report: Inflectra (infliximab); 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002778/WC500151490.pdf. Accessed 17 Feb 2014.
  4. 4.
    Siddiqui MAA, Scott LJ. Infliximab: a review of its use in Crohn’s disease and rheumatoid arthritis. Drugs. 2005;65:2179–208.PubMedCrossRefGoogle Scholar
  5. 5.
    Keating GM, Perry CM. Infliximab: an updated review of its use in Crohn’s disease and rheumatoid arthritis. BioDrugs. 2002;16(2):111–48.PubMedCrossRefGoogle Scholar
  6. 6.
    Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605–12.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613–20.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Park W, Jaworski J, Brzezicki J, et al. A randomised, double-blind, parallel-group, phase 1 study comparing the pharmacokinetics, safety and efficacy of CT-P13 and infliximab in patients with active ankylosing spondylitis: 54 week results from the PLANETAS study [abstract no. FRI0421]. 14th Annual Congress of the European League Against Rheumatism, Madrid; 12–15 Jun 2013.Google Scholar
  9. 9.
    Yoo DH, Racewicz A, Brzezicki J, et al. A phase 3 randomised controlled trial to compare CT-P13 with infliximab in patients with active rheumatoid arthritis: 54 week results from the PLANETRA study [abstract no. OP0068]. 14th Annual Congress of the European League Against Rheumatism, Madrid; 12–15 Jun 2013.Google Scholar
  10. 10.
    Yoo D, Yagensky A, Toncheva A, et al. Impact of CT-P13 and originator infliximab treatment on quality of life derived from the Health Assessment Questionnaire (AQ) and Short-Form 36 (SF-36) from a randomized, double-blind trial in patients with active RA [abstract no. 2392]. ACR/ARHP Annual Meeting, San Diego; 26–30 Oct 2013.Google Scholar
  11. 11.
    Park W, Miranda P, Brzosko M, et al. Efficacy and safety of CT-P13 (infliximab biosimilar) over two years in patients with ankylosing spondylitis: comparison between continuing with CT-P13 and switching from infliximab to CT-P13 [abstract no. L15]. ACR/ARHP Annual Meeting, San Diego; 26–30 Oct 2013.Google Scholar
  12. 12.
    Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (infliximab biosimilar) over two years in patients with rheumatoid arthritis: comparison between continued CT-P13 and switching from infliximab to CT-P13 [abstract no. L1]. ACR-ARHP Annual Meeting, San Diego; 26–30 Oct 2013.Google Scholar
  13. 13.
    Putrik P, Ramiro S, Kvien TK, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis. 2014;73:198–206.PubMedCrossRefGoogle Scholar
  14. 14.
    Putrik P, Ramiro S, Kvien TK, et al. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country’s wealth? Ann Rheum Dis. 2013. doi: 10.1136/annrheumdis-2013-203819.
  15. 15.
    Brodszky V, Pentek M, Baji P, et al. Budget impact analysis of biosimilar infliximab treatment for rheumatoid arthritis in six Central European countries [abstract no. PMS21]. Value Health. 2013;16(7):A558.CrossRefGoogle Scholar
  16. 16.
    McCarthy G, Ebel Bitoun C, Guy H. Introduction of an infliximab biosimilar (CT-P13): a five-year budget impact analysis for the treatment of rheumatoid arthritis in Ireland [abstract no. PMS22]. Value Health. 2013;16(7):A558.CrossRefGoogle Scholar
  17. 17.
    European Medicines Agency. Remsima: summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002576/WC500150871.pdf. Accessed 19 Dec 2013.
  18. 18.
    European Medicines Agency. Inflectra: summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002778/WC500151489.pdf. Accessed 19 Dec 2013.
  19. 19.
    Dorner T, Strand V, Castaneda-Hernandez G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72(3):322–8.PubMedCrossRefGoogle Scholar
  20. 20.
    US Food and Drug Administration. Quality considerations in demonstrating biosimilarity to a reference protein product: draft guidance; 2012. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291134.pdf. Accessed 13 Jan 2014.
  21. 21.
    Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000;343(22):1594–602.PubMedCrossRefGoogle Scholar
  22. 22.
    St Clair EW, Van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50(11):3432–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–85.PubMedCrossRefGoogle Scholar
  25. 25.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.PubMedCrossRefGoogle Scholar
  26. 26.
    van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Antoni CE, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005;64:1150–7.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Gottlieb AB, Evans R, Li S, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2004;51(4):534–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366(9494):1367–74.PubMedCrossRefGoogle Scholar
  31. 31.
    Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10(4):391–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.AdisNorth ShoreNew Zealand

Personalised recommendations