Biosimilar insulins: guidance for data interpretation by clinicians and users

Abstract

Biosimilar insulins are approved copies of insulins outside patent protection. Advantages may include greater market competition and potential cost reduction, but clinicians and users lack a clear perspective on ‘biosimilarity’ for insulins. The manufacturing processes for biosimilar insulins are manufacturer‐specific and, although these are reviewed by regulators there are few public data available to allow independent assessment or review of issues such as intrinsic quality or batch‐to‐batch variation. Preclinical measures used to assess biosimilarity, such as tissue and cellular studies of metabolic activity, physico‐chemical stability and animal studies of pharmacodynamics, pharmacokinetics and immunogenicity may be insufficiently sensitive to differences, and are often not formally published. Pharmacokinetic and pharmacodynamic studies (glucose clamps) with humans, although core assessments, have problems of precision which are relevant for accurate insulin dosing. Studies that assess clinical efficacy and safety and device compatibility are limited by current outcome measures, such as glycated haemoblobin levels and hypoglycaemia, which are insensitive to differences between insulins. To address these issues, we suggest that all comparative data are put in the public domain, and that systematic clinical studies are performed to address batch‐to‐batch variability, delivery devices, interchangeability in practice and long‐term efficacy and safety. Despite these challenges biosimilar insulins are a welcome addition to diabetes therapy and, with a transparent approach, should provide useful benefit to insulin users.

Similar pharmacokinetics and pharmacodynamics of rapid‐acting insulin lispro products SAR342434 and US‐ and EU‐approved Humalog in subjects with type 1 diabetes

“…Currently, public availability of these data is fairly limited (particularly data concerning good manufacturing practices). It is imperative that such data are publically accessible, particularly for studies such as clamp studies which are explicitly requested by regulatory authorities, to allow independent assessment and review . To our knowledge, no rapid‐acting biosimilar/follow‐on insulin clamp data have been published to date.…”

“…The results of this single-dose crossover study demonstrate the similarity of SAR342434 insulin lispro solution for injection to commercially available EU-and US-approved Humalog products in terms of to allow independent assessment and review. 6 To our knowledge, no rapid-acting biosimilar/follow-on insulin clamp data have been published to date.…”

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…This is because biologics are large and structurally complex, meaning that, unlike the characterisation of generics, current analytical methodology may not be able to detect or characterise all relevant structural and functional differences between biologics, a distinction that is also noted in the FDA guidance on demonstrating biosimilarity and the Australian Therapeutic Goods Administration (TGA) biologic nomenclature consultation [3, 11]. Data on the efficacy and safety of initiating therapy with a biosimilar versus with an originator biologic, generated as part of regulatory approval and post-approval phases, have been widely reviewed [12–14] and are not the focus of the current article.…”

Introduction of biosimilar insulins in Europe

“…However, clinicians and people with diabetes may not understand the concept of biosimilarity and how these medications are similar and not identical to their reference products. Preclinical and clinical data of the LY IGlar programme previously were reviewed by Heinemann et al in 2015 [4]; the current review extends and updates the previous report and includes data from the newly approved biosimilar MK-1293 insulin glargine (MK IGlar) (Lusduna â ). In this review, we define biosimilar medicines, describe EU regulatory requirements for biosimilar basal insulins, present the development programmes of LY IGlar and MK IGlar, and outline potential benefits and concerns relevant from a clinical perspective.…”