In early August, the South Korean Food and Drug Administration approved marketing of Celltrion’s Remsima, a medication that is a biosimilar to Johnson & Johnson’s Remicade (infliximab). This is thought to be the first monoclonal antibody for treating rheumatoid arthritis to be officially approved as a biosimilar anywhere in the world.
Biosimilar (or “follow-on” biological) medications are the rough biologic medication equivalent of generic drugs. However, there are more regulatory hoops for the biosimilar to jump through.
“The approval of generic medicines is based on the principle that the active ingredient is an exact copy of the innovator medication, because we can characterize the product chemically,” says Janet Woodcock, MD, director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) in Silver Springs, Md. “With complex proteins and products such as the biologic medications, we are not able to characterize them to that extent.”
Concerns Over Efficacy
To address these concerns, the FDA published guidance on what regulators will be assessing when reviewing applications for marketing authority. There will be physical, chemical, and functional comparisons made between the biosimilar and the original medication. Depending on what is learned from this stage, there may be pharmacokinetic studies in humans and possibly a full-on clinical trial between both medications.
“One interesting difference is that the design of the clinical studies to assess biosimilarity will not be the same as that used to assess the efficacy of novel therapeutic agents,” says Jonathan Kay, MD, director of clinical research in the division of rheumatology and professor of medicine at the University of Massachusetts Medical School in Worcester. “Head-to-head studies comparing the biosimilar to the innovator biopharmaceutical will need to demonstrate that the biosimilar’s efficacy is similar to that of the innovator at all time points within a prespecified range, and that there are no significant differences in safety or immunogenicity between the two biopharmaceuticals.”
Should they be either less or more effective during these studies, they cannot be biosimilar and must go through the new drug application process.
“The question is, What is good enough in this context?” says Dr. Woodcock, who is a rheumatologist. “We expect that doctors using the biosimilar drug will get the same results as those who prescribe the innovator medication.”
Lower Costs Possible
By definition, biosimilar drugs will not have a major impact on patients clinically, but they may help alleviate some financial concerns. It is thought that biosimilars may cost 30% to 50% less than the innovator medication.
Currently, biologic medications approved using one manufacturing method would essentially have to start over with a new drug application to make a change in the way the medication is made. The newer medications can take advantage of manufacturing advances occurring since the first drug was launched. In addition, the truncated approval process brings savings that may be seen in lower prices.
“I know the rheumatology community is very concerned about biosimilars and we at CDER fully expect any biosimilar approved to have the same properties as the innovators,” says Dr. Woodcock. “At the clinical level, by the time the FDA approves, the rheumatologists should have a high level of confidence that one is pretty much the same as the other.”
Dr. Kay agrees, noting, “If a biosimilar successfully gets through the specified regulatory approval process, I would be very comfortable prescribing it to my patients.”
There are 11 medications in the FDA pipeline. Dr. Woodcock could not say when the first one might come to market. She says that will depend on when sponsors can complete the studies and comparisons that have to be done.
Kurt Ullman is a freelance writer based in Indiana.
