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Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, April 2015 (Download this PDF).

  • Publisher: U.S. Department of Health and Human Services Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)
  • Summary: This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product (hereinafter proposed product) is biosimilar to a reference product for purposes of the submission of a marketing application under section 351(k) of the Public Health Service Act

Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product, April 2015 (Download this PDF).

  • Publisher: U.S. Department of Health and Human Services Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)
  • Summary: This guidance describes the Agency’s current thinking on factors to consider when demonstrating that a proposed therapeutic protein product (hereinafter proposed product or proposed biosimilar product) is highly similar to a reference product licensed under section 351(a) of the Public Health Service Act (PHS Act) for the purpose of submitting a marketing application under section 351(k) of the PHS Act.

Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues, December 2014 (Download this PDF).

  • Publisher: European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP)
  • Summary: The Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/05 Rev.1) lays down the non-clinical and clinical requirements for a similar biological medicinal product (“biosimilar”).

Guidelines on evaluation of similar biotherapeutic products (SBPs), 2013. (Download this PDF).

  • Publisher: World Health Organization

Summary: These Guidelines apply to well-established and well-characterized biotherapeutic products such as recombinant DNA-derived therapeutic proteins. Vaccines and
Annex 255plasma-derived products and their recombinant analogues, for which WHO Recommendations and regulatory guidance are available elsewhere are excluded from the scope of this document.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act). (Download this PDF).

  • Publisher: U.S. Food and Drug Administration
  • Summary: Congress, through the Biologics Price Competition and Innovation Act (BPCI Act) of 2009, created an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-approved biological product. This pathway was established as a way to provide more treatment options, increase access to lifesaving medications, and potentially lower health care costs through competition.

 

 
 

Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade

  • Authors: Ilias A, Szanto K, Gonczi L, Kurti Z, Golovics PA, Farkas K, Schafer E, Szepes Z, Szalay B, Vincze A, Szamosi T, Molnar T, Lakatos PL.
  • Citation: Clin Gastroenterol Hepatol. 2019 Nov;17(12):2506-2513.e2. doi: 10.1016/j.cgh.2018.12.036. Epub 2019 Jan 8.

  • Conclusions: The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial (Download this PDF).

  • Authors: Goll GL, Jørgensen KK, Sexton J, Olsen IC, Bolstad N, Haavardsholm EA, Lundin KEA, Tveit KS, Lorentzen M, Berset IP, Fevang BTS, Kalstad S, Ryggen K, Warren DJ, Klaasen RA, Asak Ø, Baigh S, Blomgren IM, Brenna Ø, Bruun TJ, Dvergsnes K, Frigstad SO, Hansen IM, Hatten ISH, Huppertz-Hauss G, Henriksen M, Hoie SS, Krogh J, Midtgard IP, Mielnik P, Moum B, Noraberg G, Poyan A, Prestegård U, Rashid HU, Strand EK, Skjetne K, Seeberg KA, Torp R, Ystrøm CM, Vold C, Zettel CC, Waksvik K, Gulbrandsen B, Hagfors J, Mørk C, Jahnsen J, Kvien TK.
  • Citation: J Intern Med. 2019 Jun;285(6):653-669. doi: 10.1111/joim.12880. Epub 2019 Apr 12. PMID: 30762274; PMCID: PMC6850326.
  • Conclusion: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial

  • Authors: Jørgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, Lundin KEA, Mørk C, Jahnsen J, Kvien TK.
  • Citation: Lancet. 2017 Jun 10;389(10086):2304-2316. doi: 10.1016/S0140-6736(17)30068-5. Epub 2017 May 11.

  • Conclusions: The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases.

The design of clinical trials to support the switching and alternation of biosimilars.

  • Authors: Faccin F, Tebbey P, Alexander E, Wang X, Cui L, Albuquerque T.
  • Citation: Expert Opin Biol Ther. 2016 Dec;16(12):1445-1453. doi: 10.1080/14712598.2017.1238454. Epub 2016 Sep 27.
  • Conclusions: As currently designed, biosimilar clinical trials provide insufficient information to support switching or alternating between originator products and their biosimilars. Lack of regulatory guidance contributes to this void. More robust data are required to inform the safety and efficacy of switching or alternating therapies, particularly regarding immunogenicity risks. Studies that also include alternations of therapy are needed to address these knowledge gaps.

Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima.

  • Authors: Ben-Horin S, Yavzori M, Benhar I, Fudim E, Picard O, Ungar B, Lee S, Kim S, Eliakim S, Chowers Y.
  • Citation: Gut. 2016 Jul;65(7):1132-8. doi: 10.1136/gutjnl-2015-309290. Epub 2015 Apr 20.

  • Conclusions: Anti-Remicade antibodies in patients with IBD recognise and functionally inhibit Remsima to a similar degree, suggesting similar immunogenicity and shared immunodominant epitopes on these two infliximab agents. In contrast, anti-adalimumab antibodies do not cross-react with Remsima or Remicade.

Harmonization of Infliximab and Anti-Infliximab Assays Facilitates the Comparison Between Originators and Biosimilars in Clinical Samples (Download this PDF).

  • Authors: Gils A, Van Stappen T, Dreesen E, Storme R, Vermeire S, Declerck PJ.
  • Citation: Inflamm Bowel Dis. 2016 Apr;22(4):969-75. doi: 10.1097/MIB.0000000000000709. PMID: 26954707.

  • Conclusions: The assay for therapeutic drug monitoring of Remicade can also be used to determine Remsima and Inflectra concentrations. Anti-drug antibody assays for biosimilars were developed. Anti-Remicade antibodies cross-react with infliximab biosimilars and reveal consistent negative/positive anti-drug antibody responses and highly correlated titers.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort (Download this PDF).

  • Authors: Gecse KB, Lovász BD, Farkas K, Banai J, Bene L, Gasztonyi B, Golovics PA, Kristóf T, Lakatos L, Csontos ÁA, Juhász M, Nagy F, Palatka K, Papp M, Patai Á, Lakner L, Salamon Á, Szamosi T, Szepes Z, Tóth GT, Vincze Á, Szalay B, Molnár T, Lakatos PL.
  • Citation: J Crohns Colitis. 2016 Feb;10(2):133-40. doi: 10.1093/ecco-jcc/jjv220. Epub 2015 Dec 10. PMID: 26661272.

  • Conclusions: This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions.

     
 

A randomised, double-blind, multicentre, parallel-group, prospective study comparing thepharmacokinetics, safety, and efficacy of CT-P13and innovator infliximab in patients with ankylosingspondylitis: the PLANETAS study

  • Authors: Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, Mikazane H, Gutierrez-Ureña S, Lim M, Lee YA, Lee SJ, Kim H, Yoo DH, Braun J.
  • Citation: Ann Rheum Dis. 2013 Oct;72(10):1605-12. doi: 10.1136/annrheumdis-2012-203091. Epub 2013 May 16. PMID: 23687259; PMCID: PMC3786643.
  • Conclusion: The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

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 (Download this PDF).

  • Authors: Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, Kovalenko V, Prodanovic N, Abello-Banfi M, Gutierrez-Ureña S, Morales-Olazabal L, Tee M, Jimenez R, Zamani O, Lee SJ, Kim H, Park W, Müller-Ladner U.
  • Citation: Ann Rheum Dis. 2013 Oct;72(10):1613-20. doi: 10.1136/annrheumdis-2012-203090. Epub 2013 May 16. PMID: 23687260; PMCID: PMC3786641.
  • Conclusion:  CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX.

Non‐pharmacological Effects in Switching Medication: The Nocebo Effect in Switching from Originator to Biosimilar Agent (Download this PDF)

  • Authors: Kristensen LE, Alten R, Puig L, Philipp S, Kvien TK, Mangues MA, van den Hoogen F, Pavelka K, Vulto AG.
  • Citation: BioDrugs. 2018 Oct;32(5):397-404. doi: 10.1007/s40259-018-0306-1. PMID: 30269270; PMCID: PMC6182448.
  • Conclusion:

    In this paper, we propose three key strategies to help mitigate the nocebo effect in clinical practice when switching patients from reference biologic to biosimilar: positive framing, increasing patient and healthcare professionals’ understanding of biosimilars and utilising a managed switching programme.

The nocebo effect of drugs (Download this PDF)

  • Authors: Planes S, Villier C, Mallaret M.
  • Citation: Pharmacol Res Perspect. 2016 Apr; 4(2): e00208. Published online 2016 Mar 17. doi: 10.1002/prp2.208. PMCID: PMC4804316. PMID: 27069627.
  • Summary: Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.

WHO Expert Committee on Biological Standardization, Sixtieth Report – (Download this PDF) 

  • The intention of this document is to provide globally acceptable principles for licensing biotherapeutic products that are claimed to be similar to biotherapeutic products of assured quality, safety, and efficacy that have been licensed based on a full licensing dossier.

European Medicines Agency, Q&A on Biosimilar Medicines – (Download this PDF)

  • This document provides a guide to biosimilar products in a Q&A format.
American Gastroenterological Association

PRODUCED IN CONJUNCTION WITH KNIGHTEN HEALTH