Although six biosimilar agents have now been approved by the U.S. Food & Drug Administration for use in rheumatology, scientific, clinical, economic and prescribing questions about the use of biosimilars abound. In fact, at the 2017 ACR/ARHP Annual Meeting in San Diego, Joseph Huffstutter, MD, a rheumatologist in private practice in Chattanooga, Tenn., said that no one has yet used biosimilars in a rheumatology practice in the U.S. To assist rheumatologists and rheumatology health professionals gain an understanding of biosimilar agents, the ACR has produced a white paper on biosimilars for rheumatic diseases.
Below we summarize some of the paper’s key points. Read the whole paper at https://www.rheumatology.org/Portals/0/Files/ACR-White-Paper-Science-Behind-Biosimilars.pdf.
The FDA defines a biosimilar as a biologic product that is “highly similar to” an approved biologic product (i.e., the reference, originator or bio-originator product) and that has “no clinically meaningful differences” in safety or effectiveness compared with the reference product.
Biosimilars should not be confused with generic medications, despite the fact that for both, pathways for regulatory approval are abbreviated when compared with the approval pathways for new drugs. Because biologics are proteins produced in living cells, biosimilars usually are not identical to their reference products.
The biosimilar manufacturer reverse engineers the biosimilar’s DNA sequence based on the primary protein sequence of the reference drug (available in the public domain) and transfects the synthesized gene into host cells, in which transcription and translation by the host cell generates the core protein of the biosimilar. Several factors integral to the manufacturing process influence the degree to which the molecular structure of the biosimilar matches that of its reference product. These include choice of host cell, which influences post-translational modifications of the protein (e.g., glycosylation), and methods used to purify and stabilize the final product. Importantly, to achieve FDA approval, a biosimilar must be highly similar in structure and function, equivalent in efficacy, and comparable in safety and immunogenicity to its reference product, despite potential slight molecular differences between the two agents.
Nomenclature for biosimilars in the U.S. uses the common nonproprietary name followed by a 4-letter suffix, so that each drug, both reference product and biosimilar, will have a unique nonproprietary name. Proprietary names, in contrast, are generated by the manufacturer and may vary from country to country for the same drug.
As of Dec. 31, 2017, the FDA had approved the following biosimilars, listed with their reference product, for use for rheumatologic conditions:
