Clinical trials for authorized biosimilars in the European Union: a systematic review

Article date: December 2016

By: Johanna Mielke, Bernd Jilma, Franz Koenig, Byron Jones in Volume 82, Issue 6, pages 1444-1457

Aim

In 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization.

Methods

We summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials.

Results

The variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same.

Conclusions

There seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity.

DOI: 10.1111/bcp.13076

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