Biosimilars: what the dermatologist should know

Abstract

Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g. cell lines), processes or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic and clinical assessment for similarity. The goal of the phase 3 clinical development programme for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints and statistical methods. Based on the clinical trial results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practising clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases.

The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy

“…The need for alternate therapies are usually driven due to issues, such as efficacy or tolerability with the previous biotherapeutical product [111]. The US FDA identifies an interchangeable biosimilar as one that “can be expected to produce the same clinical result as the reference product in any given patient and, if the biologic is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biologic and the reference product is not greater than the risk of using the reference/product without such alternation or switch” [112]. No interchangeable biosimilars have been approved in the US yet, even though a recent guidance has been finalized by the US FDA [113].…”

Biosimilars in Dermatology: Analytical, Regulatory, and Clinical Considerations: A Treatise From the Medical Board of the National Psoriasis Foundation

“…The FDA considers the data to support a finding of biosimilarity, based on the "totality of evidence," to "reduce residual uncertainty." 14,15,27 To date, eight TNF inhibitor biosimilars have been approved by the FDA, and many other biosimilars are under clinical investigation globally ( Table 3). The next decade will see many more biosimilars receiving approval as the market intensifies.…”

Heterogeneity and variation of innovator biologics

“…Biosimilars are highly similar to innovator biologics but not identical, raising questions about biosimilars' efficacy, safety and immunogenicity. 4 However, the degree of heterogeneity and variation within innovator biologics is not well understood. The purpose of this letter is to characterize data on the heterogeneity and variation within innovator biologics used in the treatment of psoriasis.…”

“…Even if Guti errez Garc ıa-Rodrigo et al forecasted an increase in this tropical dermatosis due to global warming, autochthonous CLM is still relatively infrequent in France and infants are even more rarely affected than adults. 2,4 Furthermore, Western physicians do not have sufficient knowledge of this parasitic disease, and this can delay diagnosis and effective treatment. Indeed, misdiagnosis or inappropriate treatment affects 22-58% of travellers with CLM.…”