PMID- 34596876 OWN - NLM STAT- MEDLINE DCOM- 20220222 LR - 20220331 IS - 1179-1950 (Electronic) IS - 0012-6667 (Print) IS - 0012-6667 (Linking) VI - 81 IP - 16 DP - 2021 Nov TI - Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective. PG - 1881-1896 LID - 10.1007/s40265-021-01601-2 [doi] AB - BACKGROUND: Biosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins. OBJECTIVES: The aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers. METHODS: Data on the safety, immunogenicity and interchangeability of EU-licensed mAbs and fusion proteins were examined using European Public Assessment Reports (EPARs) and postmarketing safety surveillance reports from the European Medicines Agency (EMA). As recent biosimilar approvals allow self-administration by patients by the subcutaneous route, the administration devices were also analyzed. RESULTS: Prelicensing data of EPARs (six different biosimilar adalimumabs, three infliximabs, three etanercepts, three rituximabs, two bevacizumabs, and six trastuzumabs) revealed that the frequency of fatal treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of treatment, serious adverse events (SAEs), and main immune-mediated adverse events (AEs) were comparable between the biosimilars and their reference products. The availability of new biosimilar presentations and administration devices may add to patient choice and be an emerging factor in the decision to switch patients. Analysis of postmarketing surveillance data covering up to 7 years of follow-up did not reveal any biosimilar-specific adverse effects. No product was withdrawn for safety reasons. This is in spite of considerable exposure to biosimilars in treatment-naive patients and in patients switched from the reference medicinal product to the biosimilar. Analysis of data from switching studies provided in regulatory submissions showed that single or multiple switches between the originator and its biosimilar versions had no negative impact on efficacy, safety or immunogenicity. CONCLUSIONS: In line with previous reports of prelicensing studies of biosimilar mAbs and etanercepts, this study demonstrated comparable efficacy, safety, and immunogenicity compared with the reference products. This is the first study to comprehensively analyze postmarketing surveillance data of the biosimilar mAbs and etanercept. An analysis of more than 1 million patient-treatment years of safety data raised no safety concerns. Based on these data, we argue that biosimilars approved in the EU are highly similar to and interchangeable with their reference products. Thus, additional systematic switch studies are not required to support the switching of patients. CI - (c) 2021. The Author(s). FAU - Kurki, Pekka AU - Kurki P AUID- ORCID: 0000-0002-7077-0305 AD - University of Helsinki, Lukupolku 19, 00680, Helsinki, Finland. pekka.kurki@fimea.fi. FAU - Barry, Sean AU - Barry S AD - Health Products Regulatory Authority, Dublin, Ireland. FAU - Bourges, Ingrid AU - Bourges I AD - Federal Agency for Medicines and Health Products, Brussels, Belgium. FAU - Tsantili, Panagiota AU - Tsantili P AD - National Organisation for Medicines, Cholargos, Greece. FAU - Wolff-Holz, Elena AU - Wolff-Holz E AD - Paul Ehrlich Institut, Langen, Germany. LA - eng PT - Journal Article DEP - 20211001 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Antibodies, Monoclonal) RN - 0 (Biosimilar Pharmaceuticals) RN - 0 (Immunologic Factors) SB - IM MH - Adverse Drug Reaction Reporting Systems MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Biosimilar Pharmaceuticals/*administration & dosage/adverse effects MH - Drug Approval MH - Drug Substitution MH - Drug and Narcotic Control/*legislation & jurisprudence MH - European Union MH - Humans MH - Immunologic Factors/*administration & dosage/adverse effects MH - Product Surveillance, Postmarketing MH - Therapeutic Equivalency PMC - PMC8578115 COIS- Pekka Kurki, Sean Barry, Ingrid Bourges, Panagiota Tsantili, and Elena Wolff-Holz have completed the ICMJE uniform disclosure (available upon request) and declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2021/10/02 06:00 MHDA- 2022/02/23 06:00 PMCR- 2021/10/01 CRDT- 2021/10/01 12:31 PHST- 2021/08/30 00:00 [accepted] PHST- 2021/10/02 06:00 [pubmed] PHST- 2022/02/23 06:00 [medline] PHST- 2021/10/01 12:31 [entrez] PHST- 2021/10/01 00:00 [pmc-release] AID - 10.1007/s40265-021-01601-2 [pii] AID - 1601 [pii] AID - 10.1007/s40265-021-01601-2 [doi] PST - ppublish SO - Drugs. 2021 Nov;81(16):1881-1896. doi: 10.1007/s40265-021-01601-2. Epub 2021 Oct 1.