Biosimilars fall under the umbrella of biologics, a category of drugs used to treat inflammatory bowel disease (IBD) since 1999. In the past 20 years, a number of different biologic drugs have been approved to induce and maintain remission of both UC and Crohn’s disease. Biosimilars are like generic drugs, with a key difference: The active ingredient in generic drugs is identical to that of the name-brand drugs they’re modeled after. Biosimilars aren’t exact copies of their originator drugs. Instead, as their name implies, they highly resemble the original drug. Because they aren’t identical, biosimilars have a different official name and are sold under different brand names. Here’s what you should know about biosimilars and how they’re used to treat UC. When biologic drugs for IBD gained prominence in the United States in the 2000s, they had years left on their patents. As these patents got closer to expiring, pressure grew on both the FDA and Congress to create an approval process for biologic copies. The first regulatory pathway for approval of these drugs — along with the name “biosimilars” — was created by the European Medicines Agency in 2005, according to an article published in the July 2015 issue of Current Opinion in Gastroenterology. In 2010 Congress created a pathway for FDA approval of biosimilars as part of the Affordable Care Act. It wasn’t until 2015, though, that the FDA actually approved a biosimilar drug, and not until 2016 did they approve a biosimilar drug to treat IBD. As of December 2019, there are FDA-approved biosimilars based on two different biologic drugs used to treat UC: adalimumab and infliximab. Adalimumab has five biosimilar equivalents; infliximab has four.
Are Biosimilars Effective at Treating IBD?
As noted above, biosimilars aren’t exact copies of the drugs they’re modeled after. When a compound has extremely large molecules that are created through a biological process, it’s impossible to re-create that compound exactly. If the FDA adopted such a standard for the approval of biosimilars, it would never be met. So instead of showing that they’re identical to the original drug on a molecular level, which is required for generic drugs, manufacturers of biosimilars must prove that they’re similar enough to the originals to have “no clinically meaningful difference.” This is done through clinical trials for safety and effectiveness, which account for a large share of the cost of bringing a biosimilar to market. But according to the FDA’s rules, biosimilars are required to be tested for only one indication — disease or health condition — that the originator drug is approved for. If the drug is shown to be safe and effective for this use, the FDA “extrapolates” that it’s safe and effective for all approved uses of the originator drug. For example, if a biologic drug is approved for treating rheumatoid arthritis, plaque psoriasis, UC, and Crohn’s disease, and a biosimilar version is shown to be safe and effective for rheumatoid arthritis, then the FDA will approve the biosimilar for all the other conditions as well, without testing the drug in those patient populations. This extrapolation strikes some people as potentially troublesome. “I think there are some issues related to extrapolation and safety and immunogenicity” — the developing of resistance to or an allergic reaction to a drug — in people with IBD, says Mark Gerich, MD, an IBD specialist and clinical director of the University of Colorado Crohn’s and Colitis Center in Aurora. “There weren’t really clinical trials done specifically in the IBD population prior to their approval,” Dr. Gerich adds. Still, he predicts that biosimilars will prove to be similar in effectiveness to original biologics for treating IBD.
The Future of Biosimilars
As of December 2019, a total of 26 biosimilars have been approved in the United States. But that number could grow quickly, according to Anita Afzali, MD, a gastroenterologist and the medical director of The Ohio State University Inflammatory Bowel Disease Center in Columbus. “There are more than 650 biosimilars under development,” Dr. Afzali notes, adding that most are in the early stages of development. “What’s to come in the United States will certainly be a hot topic of discussion.” So far in the United States, biosimilars for IBD have been approved for all the same uses as their originator drugs but have not been ruled “interchangeable” with those drugs. In practice, this means that pharmacists can’t substitute a biosimilar for a biologic, as they could with a generic for a brand-name drug. Afzali worries that this may become a distinction without a difference. It’s easy to imagine, she says, that an insurance company or hospital system could simply cover only the biosimilar equivalent of an original biologic. In this imagined scenario, she says, “the state or the insurance or the pharmacist is saying, ‘You have to try the biosimilar,’” even when a person has already experienced side effects from the biologic that might become worse with the biosimilar. At the very least, Afzali believes, doctors should be informed about what their patients are being given. “I think that as a prescribing provider, I need to be notified if a substitution is requested,” she says. “I should also be able to write, ‘Dispense as written,’” to prevent any substitution from taking place. For his part, Gerich predicts that hospitals will become the first widespread adopters of many biosimilar drugs — and possibly at some point not even use original biologics at all. If “you have a very sick hospitalized ulcerative colitis patient and you need to give them a large amount [of a biologic drug to help avert a colectomy (removal of the colon)], that becomes extremely costly for the hospital,” he notes. Stocking less expensive biosimilars, Gerich believes, may make pharmacy managers more willing to authorize this treatment, which means that more people could potentially avoid surgery.
The Positive Side of Biosimilars: More IBD Treatment Choices
No one doubts that biosimilars are here to stay and that they’ll take over a growing share of the biologic drug market in coming years. Afzali hopes the influx of new drugs will prompt more research on their effects in people with IBD. “We still need a lot more human and research testing,” she says, “to really evaluate the safety and efficacy of biosimilars” for individual diseases. Gerich is cautiously optimistic about the potential benefits of biosimilars. “Hopefully, safety won’t be a concern,” he says, “and it will be interesting to see what the financial outcomes are.” As Afzali notes, as long as choices aren’t taken away from doctors and patients, the availability of biosimilars can only be a good thing. “I think having more treatment options in our medicine cabinet is always appealing,” she says. Additional reporting by Quinn Phillips
