Three biosimilar products are now licensed for the treatment of rheumatic diseases in Europe. The European Medicines Agency (EMA) requires that similarity between a biosimilar and its reference product is demonstrated using a rigorous, stepwise process that includes extensive physicochemical and biological analytical testing, non-clinical pharmacology, clinical evaluations, and pharmacovigilance plans. Each step is highly sensitive to any differences between products and progressively reduces any uncertainty over similarity; all steps must be satisfied to demonstrate biosimilarity. The US Food and Drug Administration (FDA) requires a similar stringent biosimilar development process.
The etanercept biosimilar SB4 (Benepali®), recently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis, non-radiographic axial spondyloarthritis), and plaque psoriasis, is herein used to demonstrate the detailed analytical characterisation and clinical testing that are required by the EMA before biosimilars are approved for use. A comprehensive characterisation study involving >55 physiochemical and >25 biological assays demonstrated that SB4 has highly similar structural, physicochemical, and biological quality attributes to reference etanercept. A Phase I study demonstrated pharmacokinetic equivalence between SB4 and reference etanercept in healthy male subjects. Furthermore, a Phase III, randomised, controlled trial performed in patients with moderate-to-severe rheumatoid arthritis despite treatment with methotrexate (MTX) showed that SB4 was equivalent to etanercept in terms of efficacy, safety, and immunogenicity.
In conclusion, the biosimilar development process performed according to EMA or FDA guidelines is highly rigorous and comprehensive. Biosimilars such as SB4 are now available in clinical practice and are likely to improve access, reduce costs, and ultimately, improve health outcomes.
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