In the approval process for licensed biosimilars, bevacizumab paves the way for extrapolation of indications
The comprehensive development program for biosimilars is designed to ensure that there are no differences of efficacy and safety between these products and their reference agent. Although bevacizumab is indicated for the treatment of several tumour types, non-small cell lung cancer (NSCLC) is considered a more sensitive patient population than metastatic colorectal cancer (mCRC) in which to test novel biosimilars. Totality of evidence may then justify extrapolation to mCRC.
Since the launch of the first biosimilar (Omnitrope®; somatropin) in 2006, 58 biosimilars have been approved in the EU and 26 in the USA. Licensing of biosimilars has several advantages for healthcare systems: increases medication choice, lowers costs, frees up budgets to provide more treatments, supports competition and sustainability in the pharmaceutical industry, and fosters innovation.
There are, however, several potential barriers to broad uptake of biosimilars in clinical practice. Some physicians may lack knowledge of these drugs or confidence in their use and may also have restrictions in choosing or switching between them. In many cases, pharmacopeia stocking of specific biologic agents are decided by administrative bodies and hospital pharmacists without consulting prescribers – often on grounds of cost considerations alone.
Bevacizumab is the first therapeutic agent for which biosimilars are available in mCRC. Like all biosimilars, these were EMA- and FDA-approved based on submitted data confirming structural similarity and functional equivalence as well as confirmatory clinical efficacy and safety studies versus the reference product. The goal of the latter exercise is not to re-establish clinical parameters by unnecessarily repeating the entire clinical development program for the reference product, but to confirm similar benefits in the most sensitive patient population. For bevacizumab biosimilars, sponsors and regulatory bodies agreed overall response rate in patients with NSCLC was a scientifically justified endpoint to confirm similarity. Since bevacizumab exerts its mode of action – the inhibition of tumour angiogenesis – regardless of the type of cancer, based on totality of evidence the licensed indications for bevacizumab biosimilars could be extrapolated to the treatment of mCRC.
Licensing of biosimilars has a several potential advantages for healthcare systems, although there are several possible barriers to uptake. Bevacizumab biosimilars could serve as an example of extrapolation based on the totality of evidence.