The Concept of Biosimilarity

Custom Synthesis, Congress paved the way for the approval of biosimilars in 2010 with the passage of the Biologics Price Competition and Innovation Act, which created an abbreviated regulatory process for biosimilars. Five of the eleven biosimilars approved by FDA since then are for patients with cancer.

The first biosimilar to be approved in the United States, in 2015, was filgrastim-sndz (Zarxio), a biosimilar to filgrastim (Neupogen), which is used to prevent infection during chemotherapy. FDA has since approved ten other biosimilar products, including two drugs for treating cancer.

In addition to trastuzumab-dkst, FDA has also approved a biosimilar to bevacizumab (Avastin) for the treatment of multiple types of cancer. Called bevacizumab-awwb (Mvasi), the biosimilar could reach the US market by 2020, after the patent on bevacizumab expires.

And in May, FDA approved the first epoetin alfa biosimilar for the treatment of anemia caused by chronic kidney disease, chemotherapy, or the use of zidovudine in patients with HIV infection.

Manufacturers do not need to independently demonstrate the safety and effectiveness of biosimilars in large clinical trials to meet the approval standards of biosimilarity. If the same level of evidence from such trials were required for the approval of biosimilars as for the reference products, there would be less potential for cost savings, Dr. Hurvitz said.

For companies developing biosimilars, the goal is to establish biosimilarity, Sue Lim, M.D., director of the Scientific Review Staff within TBBS, said at the AACR meeting. This means that a new biosimilar product is highly similar to, and has no clinically meaningful differences from, the reference product.

The first step in establishing biosimilarity, Dr. Lim explained, is to characterize the chemical structure and biological function of the proposed biosimilar in a comparative fashion to the reference product.

“The thinking is that if a biosimilar has a highly similar structure and function as the reference product, then it should behave like the reference product—that is, be as effective and safe as the reference product in the clinical setting,” she added.

Throughout the process of establishing biosimilarity, manufacturers work with FDA to determine the amount and the type of data required at each step. During the process, manufacturers may use existing, publicly available scientific data about the safety and effectiveness of a reference product to compare with the biosimilars they are developing.