Uni Wong, MD, on What’s New in Biosimilars in 2022

Data from studies to date suggest that biosimilars for anti-tumor necrosis factor (TNF) therapies will behave similarly and can be dosed like their reference products, Uni Wong, MD, said at the the Advances in Inflammatory Bowel Disease regional meeting on April 2 in Raleigh, North Carolina.

Dr. Wong is an assistant professor of medicine in gastroenterology at the University of Maryland School of Medicine in Baltimore.

She explained, “Biosimilars are not generics. Generics are small molecules with identical quality and quantities of the active component as the reference product. Biologics, however, with their large molecules, are too complex to replicate exactly.”

The similarities between biosimilars and reference products include the primary structure, purity, safety, immunogenicity, mechanism of action, route of administration, and indications, Dr Wong said, adding, “there is no clinically meaningful difference in efficacy.” Differences can include some structural variations; manufacturing processes such as cell lines and culture and purification; stability, storage requirements, and expiration dating; and inactive components.

The biggest difference is in cost, Dr Wong explained. With the abbreviated licensing pathway for biosimilars created in the Patient Protection and Affordable Care Act, the estimated savings for in direct spending during the period 2017-2026 is $54 billion. This is largely due to the abbreviated development timeline for biosimilars. Whereas a reference product must progress from discovery through development, preclinical, phase 1, phase 2, and phase 3 at an approximate cost of $1 billion, biosimilars begin with development and progress through preclinical, phase 1 to phase 3 at costs ranging from $100 million to $200 million, Dr Wong said.

“FDA considers totality of evidence to evaluate interchangeability,” she said. The statutory criterion for interchangeability it that the product “can be expected to produce the same clinical result as the reference product in any given patient” and “in all of the reference product’s licensed conditions of use.”

In the approval process, a biosimilar can be extrapolated to any indication for which its reference product is approved following 1 comparative randomized clinical trial that demonstrates its noninferiority for any indication. For example, a biosimilar may be tested in a randomized clinical trial for rheumatoid arthritis (RA) and if successful, it may then be extrapolated for treatment of inflammatory bowel disease (IBD).

There are now 7 biosimilars for adalimumab and 4 for infliximab, Dr Wong noted. To date, studies of noninferiority and maintenance of remission in Crohn disease for infliximab biosimilars showed no difference in efficacy. The well known NOR-SWITCH study showed that changing from infliximab to a biosimilar and back had no impact on outcomes. A similar study of switches from infliximab to a biosimilar among patients with ulcerative colitis yielded essentially the same results.

One of the primary challenges in transitioning patients to biosimilars is the so-called “nocebo effect,” when a patient experiences new or worsening symptoms due to the patient’s expectation that the biosimilar will not be as effective as the original product. Dr Wong described this as the “evil brother of the placebo effect.” This problem can be addressed with patient education about biosimilars. She explained, “The University of Maryland developed a brochure explaining concept of biosimilar with a concise summary of efficacy and safety,” to help alleviate patient concerns.

Educating nurses and other staff about biosimilars is equally important, Dr Wong said. “This enhances the probability that everyone is sending the same message” when patients ask questions, she said.

Dr Wong cautioned, “Antibodies to reference products WILL cross-react to biosimilars (and vice versa),” so if a patient has developed antidrug antibodies to an anti-TNF, changing to its biosimilar will not be effective. In such cases, another mechanism of action may be required.

Summarizing, she emphasized, “Biosimilars are not generics. Data suggest that biosimilars for anti-TNFs will behave similarly to their reference products.  Dosing is the same as for the reference drug and drug assays are expected to work similarly for biosimilars.”

--Rebecca Mashaw

Wong U. What’s new in biosimilars in 2022? Presented at: Advances in Inflammatory Bowel Diseases. April 2, 2022. Raleigh, North Carolina.