Positioning Biosimilars as First-Line or Switch Therapy

Biosimilars of biologic innovator compounds appear to be as effective and safe as the reference drugs on which they are based, said Raymond Cross, MD, at the virtual Advances in Inflammatory Bowel Disease (AIBD) 2020 regional meeting on July 25.

Dr Cross, one of the co-chairs of the AIBD regional meetings for 2020, is director of the Inflammatory Bowel Disease Program at the University of Maryland School of Medicine in Baltimore.

He explained that biosimilars and their reference compounds “are rather like identical twins, who have the same DNA but slightly different fingerprints. You can’t make a precise copy of a biologic, so you can’t make a true generic, but it is possible to create a therapeutic agent that functions in an almost identical fashion.” The US Food and Drug Administration (FDA) defines a biosimilar as “a biological agent highly similar to a reference product,” with “no clinically meaningful differences in terms of safety, purity, and potency.”

However, there remain questions about biosimilars, including whether they are truly interchangeable, whether it is safe to switch a patient who achieved remission on the reference compound, and whether beginning treatment with a biosimilar is safe and effective.

Dr Cross noted that the key advantage of a biosimilar is reduced cost, which in turn makes possible wider access to these therapies worldwide and allows the use of these drugs earlier in the course of IBD, which is associated with better outcomes.

He explained that the innovator biologics account for 1% of prescriptions and 28% of medication spending. Their development required multiple randomized clinical trials to prove their safety and efficacy before they were approved by the FDA. Biosimilars, however, rely much less on clinical trials for approval and more on studies of pharmacokinetics, analytics, and pharmacodynamics, which makes them less expensive to develop and shortens the time for approval. As a result, biosimilars may cost 30% to 40% less than innovator compounds.

Still, he noted, questions remain about who actually benefits from this reduction in cost. “Is this cost savings, or cost shifting?” he asked. Third-party payers, whether governmental or private, will probably reap the greatest benefits, Dr Cross stated.

The FDA has not deemed any biosimilars now available as interchangeable, Dr Cross noted, because this designation requires that the biosimilar be subjected to trials in which the biosimilar and reference drug are switched 3 times with no loss of efficacy. Substitution, however, is allowed; this occurs when a pharmacist dispenses the biosimilar instead of the innovator compound, much as generic drugs are substituted for brand-name medications.

In real-world observational studies, Dr Cross said, the effectiveness and safety of biosimilars in de novo as well as switching has been demonstrated. He referenced the Nor-Switch study, in which Norwegian patients with IBD were switched from infliximab to the biosimilar CT-P13. In this study, researchers assessed the clinical response, remission, and adverse events in patients with active Crohn disease (CD) and ulcerative colitis (UC) treated with the biosimilar and found “high rates of clinical response.” Specifically, 7 observational studies showed 79% response in patients with CD at 8 to 14 weeks and 74% in patients with UC; at 24 to 30 weeks, 75% of patients with CD and 83% with UC showed clinical response, along with low rates of adverse events.

Observational studies of patients switching from infliximab to CT-P13 also showed very positive results, with 75% of patients with CD and 83% with UC maintaining clinical response at 48 to 63 weeks.

The greatest risk in using biosimilars may be the “nocebo effect,” Dr Cross said. “Some call this the evil cousin of the placebo effect; the patient anticipates a negative response from a change in medication and may have an increase in symptoms.” The answer to this nocebo effect, he said, is thorough patient education. At the University of Maryland, he explained, “we developed a brochure explaining the concept of biosimilars with a concise summary about safety and efficacy” for patients and also educated the nursing and ancillary staff about biosimilars, so they can answer patients’ questions. The effort has been very successful at his facility, he said, with only 2 patients refusing to switch and 19 of 20 patients who made the change remaining on biosimilar therapy after 3 to 5 infusions.

He also cautioned that these switches should not be made at “sensitive times,” such as during pregnancy or before travel. “Ideally, all patients should be in steroid-free remission, biologic remission with normal CRP and fecal calprotectin, and healed or minimally inflamed mucosa.”

“Don’t rush the change,” Dr Cross advised. “Emphasize efficacy and safety. At the University of Maryland, we emphasized that the cost savings were being reinvested in programs to offer increased patient support. And allow patients to have the final choice on the switch.”

—Rebecca Mashaw

Reference:

Cross, RK. Biosimilars: positioning in IBD as first line or switch therapy. Presented at: Advances in Inflammatory Bowel Disease 2020 regional, Chicago; July 25, 2020; virtual.