Recent approval of several trastuzumab biosimilars provide an example of how a robust clinical development program works in practice

Biosimilars are ‘similar’ but not ‘identical’ to the originator. This distinction has caused considerable anxiety for cancer clinicians and patients alike. Better understanding of the rigorous process of developing and approving biosimilars, and increasing experience of their use, should eliminate this anxiety.

Biosimilars are an increasingly central element of the cancer treatment armamentarium; the three biggest-selling cancer drugs are the monoclonal antibodies rituximab, bevacizumab, and trastuzumab. Since biosimilar versions of all these drugs are now available, it is important to understand what biosimilars are, and what they are not.

The FDA and EMA have defined biosimilars as highly similar biologic products to approved originator products with no clinically meaningful differences. However, biosimilars and originator biologics have very different approval pathways. Originator biologics require extensive basic research, establishment of a production and purification plant, and a comprehensive program of clinical trials, separately performed for each indication. By contrast, biosimilars require a production facility and mostly physicochemical and functional comparisons with the originator. Clinical trials are then performed to compare the biosimilar’s pharmacokinetic attributes, efficacy, and safety in a highly sensitive population versus the originator drug. Clinical evaluation for biosimilars is less extensive because evidence for safety and efficacy in one indication may be extrapolated across all other indications for the originator.

Extensive analytical similarity testing to establish biosimilarity relative to the originator effectively justifies abridged clinical development programs for regulatory approval of biosimilars. Although clinicians may be understandably cautious about making substitutions of biosimilars for their familiar branded products, they should be reassured that the rigorous regulatory pathway for biosimilars ensures they are appropriate options for their approved indications.

Key takeaway

Biosimilars and originator biologics have different approval pathways: originators require extensive basic research, whereas biosimilars require physicochemical and functional comparisons with the originator. Extensive analytical similarity testing establishes biosimilarity, justifying an abbreviated development and approval process.