Considerations related to comparative clinical studies for biosimilars

ABSTRACT

Introduction: Biosimilar medicines have transformed the healthcare landscape by providing improved access to life-saving medicines at a lower cost. Biosimilars are a distinct category of biologic therapeutics that enter the market after patent expiration of a reference molecule. Regulatory bodies worldwide have developed guidance to expedite the approval and entry of these drugs to the market. Biosimilar approval is based on a totality of the evidence approach, demonstrating similarity between the biosimilar and the originator in terms of physicochemical properties, quality characteristics, biological activity, safety, and efficacy.

Areas covered: This article provides an overview of the biosimilar regulatory guidelines and discusses the importance and considerations of comparative clinical studies that are performed during biosimilar development. Two review assessment reports, one each from the EMA and the FDA, are presented.

Expert opinion: The discussed case studies illustrate the importance of pharmacokinetic and pharmacodynamic studies in the regulatory approval of biosimilars. It is crucial for biosimilar developers to judiciously determine clinical parameters including biomarkers, endpoints, and acceptance criteria before executing clinical studies.

KEYWORDS:

• Biosimilar
• clinical comparability
• extrapolation
• pharmacokinetics
• pharmacodynamics
• regulatory filings

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript disclosed that they are employed at a biopharmaceutical company that develops both biosimilars and originator biologics. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• In a biosimilar development program, the aim of clinical comparative studies is to demonstrate similarity and not to re-establish efficacy and safety of the product.

• EMA and FDA have specific guidelines on how pharmacology data can demonstrate comparability of a biosimilar to reference products.

• It is pivotal for biosimilar manufacturers to cautiously design PK and PD studies and predetermine clinical parameters including biomarkers, endpoints, and acceptance criteria before executing clinical studies.

• A well-designed PK/PD study with relevant biomarker and endpoint analysis can obviate the need for clinical efficacy studies or justify small phase 3 studies that can expedite the biosimilar development program.

• Case studies discussed in the article exemplify the significant role of PK and PD studies in biosimilar development.

This box summarizes the key points contained in the article.

Additional information

Funding

This work was funded by the Department of Biotechnology, Ministry of Science and Technology (BT/COE/34/SP15097/2015).