Biosimilar Drugs for Psoriasis: Principles, Present, and Near Future

Abstract

Psoriasis is a chronic, inflammatory, lifelong disease with a high prevalence (afflicting approximately 1-5% of the population worldwide) and is associated with significant morbidity. The introduction of biologic therapies has improved the management of this disease. Multiple biologic medicines that block cytokine signaling, including tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, and infliximab) and inhibitors of interleukin (IL)-17 (brodalumab, ixekizumab, and secukinumab), IL-23 (guselkumab), or IL-12/23 (ustekinumab), are approved for the treatment of psoriasis. Despite the clinical benefits associated with use of biologics in psoriasis, many patients are not treated with biologic therapy, and access to treatment may be limited for various reasons, such as high treatment costs. Patents for many biologics have expired or will soon expire, and biosimilar versions of these agents are available or in development. A biosimilar is a biological product that is highly similar to an approved biologic (i.e., originator or reference) product, and has no clinically meaningful differences in safety, purity, or potency when compared with the reference product. Biosimilars may offer less expensive treatment options for patients with psoriasis; they also may increase access to and address problems with underutilization of biologic therapy. Biosimilar development and approval follows a well-regulated process in many countries, with guidelines developed by the European Medicines Agency, US Food and Drug Administration, and World Health Organization. Currently, several anti-TNF biosimilars are available for use in patients with psoriasis, and other monoclonal antibodies are in development. This review provides dermatologists and those who treat and/or manage psoriasis with a working knowledge of the scientific principles of biosimilar development and approval. It also examines real-world experience with biosimilars available for or used in dermatology that will enable physicians to make informed treatment decisions for their patients with psoriasis.

Funding: Pfizer Inc.

Keywords: Biologics; Biosimilars; Interchangeability; Psoriasis; Safety; Switching.

Fig. 1

Overview of biologic manufacturing process [69]. Most biologics are recombinant proteins produced through a multistep process. First, a vector containing complementary DNA for the protein of interest and a selectable marker is transferred into a suitable host cell (e.g., bacterium, mammalian cell). Next, a master cell bank is established through positive selection of transformed cells expressing the selectable marker in the presence of an antibiotic or inducing agent. A starter culture of cells is then transferred from the master cell bank to a bioreactor where, under optimal growth conditions, it can undergo large-scale expansion and recombinant protein production. Cell cultures are recovered through centrifugation, and the recombinant protein is purified from culture media through a series of chromatographic steps. The physicochemical and biological properties of the recombinant protein are extensively characterized, after which it undergoes formulation and packaging. Changes to any steps in the manufacturing process (arrows and text) can alter the safety and effectiveness of the biologic product. For example, changing the cell-expression system in which a recombinant protein is produced could alter its glycosylation patterns and, in turn, the protein’s immunogenic potential [69]. Differences in a licensed originator biologic may arise over time as a result of planned changes to its manufacturing process made by the same manufacturer [68]. Accordingly, pre-change and post-change products are compared to demonstrate that any changes to the manufacturing processes have no adverse impact on the quality of the product [68]. This comparability assessment is based on extensive knowledge about the product and existing manufacturing process as well as the nature of the manufacturing change, and is typically addressed with analytical studies [68]. The comparability assessment is distinct from the biosimilarity assessment, which requires a demonstration of no clinically meaningful differences between the potential biosimilar and originator product based on extensive comparative analytical, nonclinical, and clinical assessments [68]