In 1982, the U.S. Food and Drug Administration (FDA) approved the first biologic, a recombinant insulin. Since then, the development and use of biologics has exploded. Between 2011 and 2016, the FDA approved 85 biologics (J Allergy Clin Immunol. 2017;139:1461-1464). Use of biologics—complex, protein-based medical treatments produced by living organisms—continues to grow yearly, and they are expected to eventually outpace traditional chemical drugs as medical treatments. But despite their promise, biologics come with one big drawback: high price tags.
Enter biosimilars, the “generic” version of biologics. Biosimilars are intended to be close-enough, even interchangeable, copies of biologic drugs. They’re relatively new here in the United States; the FDA approved the first biosimilar, filgrastim-sndz (Zarxio), which is clinically similar to Neupogen, in 2015. Since then, three more biosimilars have been approved: infliximab-dyyb (Inflectra), which is similar to Remicade; etanercept-szzs (Erelzi), which is similar to Enbrel; and adalimumab-atto (Amjevita), which is similar to Humira. These biosimilars are used to treat severe Crohn’s disease, arthritis, and psoriasis. More than 50 biosimilars are currently in the development pipeline, and biologics and biosimilars may soon become important therapeutic options in all areas of medicine, including otolaryngology.
Biologics are made via complex processes involving living organisms. “Most of the biologics that are produced are from a single lab. They purify and harvest these antibodies from a mouse, chinchilla, or certain type of bacteria,” said Subinoy Das, MD, an otolaryngologist with Ohio ENT & Allergy Physicians in Columbus.
To make biosimilars, development labs “find the proteomic signature of all the proteins in the reference biologic and recreate that protein in the lab,” Dr. Das said. Recreating a complex biologic is not as simple as copying small-molecule drugs to make generics, however. “That’s simple chemistry,” Dr. Das said. “It’s much easier than trying to copy a complex monoclonal antibody that has protein folds and is very hard to replicate.”
As a result, biosimilars differ from their reference products. They have the same amino acid sequence, but “may differ in three-dimensional structure, glycosylation sites, isoform profiles, and protein aggregation,” according to Gary H. Lyman, MD, MPH, professor of medical oncology in the University of Washington’s School of Medicine in Seattle, who was quoted in a recent article for the American Society of Clinical Oncology (ASCO). “Product drift because of minor differences in manufacturing, processing, and packaging may result in meaningful differences in both biosimilars and the originator biologic over time.”