The rise of biosimilars: Balancing innovation with affordable biologic alternatives
Keywords:
Biologics, Biosimilars, Rheumatoid Arthritis, Inflammatory Bowel Disease, Stakeholder CollaborationAbstract
Background: Biologics have transformed the management of immune-mediated inflammatory conditions, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). The introduction of biosimilars—biologic medications that are highly similar and interchangeable with approved originators—has the potential to enhance market competition and improve patient access to necessary therapies. Aim of Work: This review aims to highlight the importance of collaboration among stakeholders to optimize the benefits of biosimilars and expedite their availability to patients while ensuring safety, quality, and effectiveness. Methods: The review analyzes regulatory frameworks, market dynamics, and pharmacoeconomic assessments regarding the introduction of biosimilars. It emphasizes the role of effective communication between physicians and patients, as well as the necessity for consistent treatment recommendations and reimbursement policies. Results: The findings indicate that collaboration between regulators and developers is essential to ensure the quality and safety of biosimilars. Updating pharmacoeconomic assessments and payer policies is crucial to prevent nonmedical barriers to access. Enhanced understanding of biosimilars by patients is vital to reduce nocebo effects, while well-informed physicians can guide patients effectively through treatment transitions. Conclusion: To maintain a sustainable biosimilar market and healthcare systems, stakeholders must prioritize collaboration, operations efficiency, and information exchange.
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References
Rein P, Mueller RB. Treatment with biologicals in rheumatoid arthritis: an overview. Rheumatol Ther. 2017;4:247–61.
Quartuccio L, Valent F, Pasut E, Tascini C, De Vita S. Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: a population-based study in the first two months of COVID-19 outbreak in Italy. Joint bone spine. 2020 Oct 1;87(5):439-43..
Ben-Horin S, Vande Casteele N, Schreiber S, et al. Biosimilars in inflammatory bowel disease: facts and fears of extrapolation. Clin Gastroenterol Hepatol. 2016;14:1685–96.
Kent D, Rickwood S, and Di Biase S. Disruption and maturity: the next phase of biologics. 2017; https://www.iqvia.com/-/media/iqvia/pdfs/nemea/uk/disruption_and_maturity_the_next_phase_of_biologics.pdf?_=1518214264988. Accessed 17 Dec 2019.
van den Hoven A. Biosimilar medicines clinical use: an experience-based EU perspective. 2017; https://www.medicinesforeurope.com/docs/20170713%20-%20Biosimilar%20Medicines%20Group,%20EU%20experience-AVH-US%20FDA%20Adcom.pdf. Accessed 17 Dec 2019.
Dutta B, Huys I, Vulto AG, Simoens S. Identifying key benefits in European off-patent biologics and biosimilar markets: it is not only about price!. BioDrugs. 2020 Apr;34(2):159-70.
IQVIA. The impact of biosimilar competition in Europe. 2018; https://ec.europa.eu/docsroom/documents/31642. Accessed 17 Dec 2019.
Jacoby R, Smith E, Wilkins D, et al. Winning with biosimilars. Opportunities in global markets. 2016; https://www2.deloitte.com/content/dam/Deloitte/us/Documents/life-sciences-health-care/us-lshc-biosimilars-whitepaper.pdf. Accessed 17 Dec 2019.
Mulcahy AW, Hlavka JP, and Case SR. Biosimilar cost savings in the United States: initial experience and future potential. 2017; https://www.rand.org/pubs/perspectives/PE264.html. Accessed 17 Dec 2019.
QuintilesIMS. The impact of biosimilar competition in Europe. 2017; http://ec.europa.eu/growth/content/impact-biosimilar-competition-price-volume-and-market-share-update-2017-0_en. Accessed 17 Dec 2019.
Glintborg B, Sorensen J, Hetland ML. Does a mandatory non-medical switch from originator to biosimilar infliximab lead to increased use of outpatient healthcare resources? A register-based study in patients with inflammatory arthritis. RMD Open. 2018;4:e000710.
Glintborg B, Sørensen IJ, Loft AG, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis. 2017;76:1426.
Glintborg B, Loft AG, Omerovic E, et al. To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry. Ann Rheum Dis 2019;78:192.
Al-Sabbagh A, Olech E, McClellan JE, et al. Development of biosimilars. Semin Arthritis Rheum. 2016;45:S11–8.
Vulto AG and Jaquez OA. The process defines the product: what really matters in biosimilar design and production? Rheumatology (Oxford) 2017;56:iv14–29.
Tsuruta LR, Lopes dos Santos M, and Moro AM. Biosimilars advancements: moving on to the future. Biotechnol Prog 2015;31:1139–49.
Isaacs J, Goncalves J, Strohal R, et al. The biosimilar approval process: how different is it? Consider Med. 2017;1:3–6.
US Food and Drug Administration. Development of therapeutic protein biosimilars: comparative analytical assessment and other quality-related considerations. Guidance for industry. 2019; https://www.fda.gov/downloads/drugs/guidances/ucm291134.pdf. Accessed 17 Dec 2019.
European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. 2014; http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf. Accessed 17 Dec 2019.
US Food and Drug Administration. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. 2015; https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed 17 Dec 2019.
Declerck P and Farouk Rezk M. The road from development to approval: Evaluating the body of evidence to confirm biosimilarity. Rheumatology (Oxford) 2017;56:iv4–iv13.
Bui LA, Hurst S, Finch GL, et al. Key considerations in the preclinical development of biosimilars. Drug Discov Today. 2015;20(Suppl 1):3–15.
Weise M, Bielsky M-C, De Smet K, et al. Biosimilars: what clinicians should know. Blood. 2012;120:5111–7.
Berkowitz SA, Engen JR, Mazzeo JR, et al. Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars. Nat Rev Drug Discov. 2012;11:527–40.
Háda V, Bagdi A, Bihari Z, et al. Recent advancements, challenges, and practical considerations in the mass spectrometry-based analytics of protein biotherapeutics: a viewpoint from the biosimilar industry. J Pharm Biomed Anal. 2018;161:214–38.
United States Food & Drug Administration. Guidance for industry: E9 statistical principles for clinical trials. 1998; https://www.fda.gov/media/71336/download. Accessed 17 Dec 2019.
European Medicines Agency. Note for guidance on statistical principles for clinical trials. 1998; https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-9-statistical-principles-clinical-trials-step-5_en.pdf. Accessed 17 Dec 2019.
US Food and Drug Administration. Non-inferiority clinical trials to establish effectiveness. 2016; https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-inferiority-clinical-trials. Accessed 17 Dec 2019.
Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2–8.
Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. 2016;2:e000154.
Jairath V, Zou GY, Parker CE, et al. Placebo response and remission rates in randomised trials of induction and maintenance therapy for ulcerative colitis. Cochrane Database Syst Rev 2017;9:Cd011572.
Ma C, Guizzetti L, Panaccione R, et al. Systematic review with meta-analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis. Aliment Pharmacol Ther. 2018;47:1578–96.
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;72:1613–20.
Ye BD, Pesegova M, Alexeeva O, et al. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study. Lancet. 2019;393:1699–707.
Meyer A, Rudant J, Drouin J, et al. Effectiveness and safety of reference infliximab and biosimilar in Crohn disease: a French equivalence study. Ann Intern Med. 2019;170:99–107.
Meyer A, Rudant J, Drouin J, et al. The effectiveness and safety of infliximab compared with biosimilar CT-P13, in 3112 patients with ulcerative colitis. Aliment Pharmacol Ther. 2019;50:269–77.
Kolar M, Duricova D, Bortlik M, et al. Infliximab biosimilar (Remsima™) in therapy of inflammatory bowel diseases patients: experience from one tertiary inflammatory bowel diseases centre. Dig Dis. 2017;35:91–100.
Farkas K, Rutka M, Balint A, et al. Efficacy of the new infliximab biosimilar CT-P13 induction therapy in Crohn’s disease and ulcerative colitis—experiences from a single center. Expert Opin Biol Ther. 2015;15:1257–62.
Farkas K, Rutka M, Golovics PA, et al. Efficacy of infliximab biosimilar CT-P13 induction therapy on mucosal healing in ulcerative colitis. J Crohns Colitis. 2016;10:1273–8.
Balint A, Rutka M, Kolar M, et al. Infliximab biosimilar CT-P13 therapy is effective in maintaining endoscopic remission in ulcerative colitis—results from multicenter observational cohort. Expert Opin Biol Ther. 2018;18:1181–7.
Tursi A, Allegretta L, Chiri S, et al. Effectiveness and safety of infliximab biosimilar CT-P13 in treating ulcerative colitis: a real-life experience in IBD primary centers. Minerva Gastroenterol Dietol. 2017;63:313–8.
European Medicines Agency. Guideline on similar biological medicinal products containing monoclonal antibodies—non-clinical and clinical issues. 2014; http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128686.pdf. Accessed 17 Dec 2019.
Doevendans E, Schellekens H. Immunogenicity of innovative and biosimilar monoclonal antibodies. Antibodies (Basel, Switzerland). 2019;8:21.
Jani M, Dixon WG, Chinoy H. Drug safety and immunogenicity of tumour necrosis factor inhibitors: the story so far. Rheumatology (Oxford). 2018;57:1896–907.
US Food and Drug Administration. Immunogenicity testing of therapeutic protein products—developing and validating assays for anti-drug antibody detection. 2019; https://www.fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-testing-therapeutic-protein-products-developing-and-validating-assays-anti-drug. Accessed 17 Dec 2019.
European Medicines Agency. Guideline on immunogenicity assessment of therapeutic proteins. 2017; https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-immunogenicity-assessment-therapeutic-proteins-revision-1_en.pdf. Accessed 17 Dec 2019.
Kim JS, Kim SH, Kwon B, et al. Comparison of immunogenicity test methods used in clinical studies of infliximab and its biosimilar (CT-P13). Expert Rev Clin Immunol. 2015;11:33–41.
Schreitmüller T, Barton B, Zharkov A, et al. Comparative immunogenicity assessment of biosimilars. Future Oncol. 2019;15:319–29.
Gorovits B, Baltrukonis DJ, Bhattacharya I, et al. Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab. Clin Exp Immunol. 2018;192:348–65.
Vermeire S, Gils A, Accossato P, et al. Immunogenicity of biologics in inflammatory bowel disease. Therap Adv Gastroenterol 2018;11:1756283x17750355.
Billmeier U, Dieterich W, Neurath MF, et al. Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases. World J Gastroenterol. 2016;22:9300–13.
Cohen MD, Keystone E. Rituximab for rheumatoid arthritis. Rheumatol Ther. 2015;2:99–111.
Nakken B, Papp G, Bosnes V, et al. Biomarkers for rheumatoid arthritis: from molecular processes to diagnostic applications-current concepts and future perspectives. Immunol Lett. 2017;189:13–8.
Cazap E, Jacobs I, McBride A, et al. Global acceptance of biosimilars: importance of regulatory consistency, education, and trust. Oncologist. 2018;23:1188–98.
Kirchhoff CF, Wang XM, Conlon HD, et al. Biosimilars: key regulatory considerations and similarity assessment tools. Biotechnol Bioeng. 2017;114:2696–705.
Takeuchi T, Yamanaka H, Tanaka Y, et al. Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis. Mod Rheumatol. 2015;25:817–24.
Tanaka Y, Yamanaka H, Takeuchi T, et al. Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab. Mod Rheumatol. 2017;27:237–45.
Joensuu JT, Huoponen S, Aaltonen KJ, et al. The cost-effectiveness of biologics for the treatment of rheumatoid arthritis: a systematic review. PLoS One. 2015;10:e0119683.
Ferrario A, Humbert T, Kanavos P, et al. Strategic procurement and international collaboration to improve access to medicines. Bull World Health Organ. 2017;95:720–2.
Severs M, Oldenburg B, van Bodegraven AA, et al. The economic impact of the introduction of biosimilars in inflammatory bowel disease. J Crohns Colitis. 2017;11:289–96.
Gulacsi L, Pentek M, Rencz F, et al. Biosimilars for the management of inflammatory bowel diseases: economic considerations. Curr Med Chem. 2019;26:259–69.
Colombel JF, Ungaro R, Aggarwal S, et al. P692 Efficacy and safety of early biologic treatment of Crohn’s disease in adult and paediatric patients: a systematic review. J Crohns Colitis. 2018;12:S461.
Panaccione R, Colombel JF, Bossuyt P, et al. Long-term cost-effectiveness of tight control for Crohn’s disease with adalimumab-based treatment: economic evaluation beyond 48 weeks of CALM trial. J Crohns Colitis. 2018;1:S074–5.
Pillai N, Dusheiko M, Burnand B, et al. A systematic review of cost-effectiveness studies comparing conventional, biological and surgical interventions for inflammatory bowel disease. PLoS One. 2017;12:e0185500.
Puolakka K, Kautiainen H, Möttönen T, et al. Early suppression of disease activity is essential for maintenance of work capacity in patients with recent-onset rheumatoid arthritis: five-year experience from the FIN-RACo trial. Arthritis Rheum. 2005;52:36–41.
Anis A, Zhang W, Emery P, et al. The effect of etanercept on work productivity in patients with early active rheumatoid arthritis: results from the COMET study. Rheumatology. 2009;48:1283–9.
Cheung WY, Kornelsen EA, Mittmann N, et al. The economic impact of the transition from branded to generic oncology drugs. Curr Oncol. 2019;26:89–93.
Berns M, Hommes DW. Anti-TNF-alpha therapies for the treatment of Crohn’s disease: the past, present and future. Expert Opin Investig Drugs. 2016;25:129–43.
Jha A, Upton A, Dunlop WC, et al. The budget impact of biosimilar infliximab (Remsima®) for the treatment of autoimmune diseases in five European countries. Adv Ther. 2015;32:742–56.
Brodszky V, Baji P, Balogh O, et al. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries. Eur J Health Econ. 2014;15(Suppl 1):S65–71.
Simon Kucher & Partners. Payers’ price & market access policies supporting a sustainable biosimilar medicines market. 2016; https://www.medicinesforeurope.com/wp-content/uploads/2016/09/Simon-Kucher-2016-Policy-requirements-for-a-sustainable-biosimilar-market-FINAL-report_for-publication2.pdf. Accessed 17 Dec 2019.
Khraishi M, Stead D, Lukas M, et al. Biosimilars: a multidisciplinary perspective. Clin Ther. 2016;38:1238–49.
Zheng MK, Shih DQ, Chen GC. Insights on the use of biosimilars in the treatment of inflammatory bowel disease. World J Gastroenterol. 2017;23:1932–43.
Mitrev N, Vande Casteele N, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;46:1037–53.
Papamichael K, Juncadella A, Wong D, et al. Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared to standard of care in patients with inflammatory bowel disease. J Crohns Colitis. 2019;13:976–81.
Reinisch W, Eser A, Schreiber S, et al. Body weight and rapid clearance determine early formation of anti-drug antibodies against infliximab. United European Gastroenterol J. 2017;5(suppl 1):A102.
Ricciuto A, Dhaliwal J, Walters TD, et al. Clinical outcomes with therapeutic drug monitoring in inflammatory bowel disease: a systematic review with meta-analysis. J Crohns Colitis. 2018;12:1302–15.
Roblin X, Riviere P, Flamant M, et al. Proactive therapeutic drug monitoring of TNF antagonists in inflammatory bowel disease. Inflamm Bowel Dis. 2018;24:1904–9
Ben-Horin S. Drug level-based anti-tumor necrosis factor therapy: ready for prime time? Gastroenterology. 2015;148:1268–71.
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