Streamlining biosimilar development based on 20 years’ experience

ABSTRACT

Introduction

Biosimilar clinical programs could be streamlined by prudent application of improved methodologies and knowledge accumulated over the past 20 years. This review focuses on whether complex comparative efficacy trials are routinely needed and how to achieve a more tailored approach to biosimilar development.

Areas covered

Key learnings over the past 20 years are summarized. It is noted that a one size fits all approach to biosimilar development is not appropriate: biological medicines fall within a wide spectrum of complexity, with blurring at the interface between biological products and small molecules. The interrelationship between quality, potency, pharmacokinetics, pharmacology, immunogenicity, efficacy, and safety are reviewed. Current regulatory thinking is reviewed with a look into what future challenges lie ahead.

Expert opinion

To tailor regulatory requirements for marketing approval of biosimilars, it is proposed that a biosimilarity report be introduced. This report would integrate quality, pharmacology, immunogenicity, efficacy and safety findings and address how the clinical program could be tailored based on the totality of evidence.

KEYWORDS:

• Clinical evidence
• comparative efficacy trial
• tailored development
• totality of data
• biosimilar
• similar biological medicine

Article highlights

• The regulatory hurdles to achieve marketing approval faced by biosimilars far exceed those for small generic drugs.

• Clinically relevant quality differences between the biosimilar and reference product can usually be identified by physico-chemical methods and could negate the need for complex comparative efficacy trials, and add cost so deterring development of some biosimilars.

• UK MHRA has progressed to a view that in most cases, a comparative efficacy trial may not be necessary if sound scientific rationale supports this approach. Other major regulatory agencies in most cases require a comparative efficacy trial.

• An integrated presentation of the quality, in vitro and clinical data would present a clearer case to all regulators for waiving the need for complex comparative efficacy trials.

• As a first step in addressing this, it is proposed to introduce a biosimilarity report that could explain how the totality of data supports biosimilarity.

Declaration of interest

C Nick is an employee of Parexel. Parexel’s clients include those sponsoring the development of biosimilars as well as innovator companies. The content of this review is not in any way influenced by any of Parexel’s clients and does not serve the financial interests of the author or Parexel. The author has no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.