Framing the Switch to Biosimilars for Patients and Providers

Preliminary evidence from a meta-analysis of studies that compared biosimilars and their reference anti-tumor necrosis factor (TNF) biologics demonstrated pharmacokinetic equivalence and no consistent adverse events between the groups, said Russell Cohen, MD, during his presentation at the virtual Advances in Inflammatory Bowel Disease (AIBD) regional meeting on August 22.

Dr Cohen is director of the Inflammatory Bowel Disease Center at UChicago Medicine and professor of medicine at the Pritzker School of Medicine.

“Biosimilars are big money,” he stated. In 2017, they represented 37% of drug spending but only 2% of all prescriptions written. In 2018, biologics earned $215 billion—a 50% increase from 2014—and account for 93% of net drug spending over the same 4-year period.

Biologic therapeutics, such as monoclonal antibody medications, are derived from genetically engineered living cells or organisms, Dr Cohen explained, and a biosimilar product must be “highly similar to the reference product with no clinically meaningful difference in terms of safety profile, purity, and potency.” Biosimilar manufacturing does not have access to same cell line but does have access to the genetic code required to produce these very complex, large molecules. The objective in biosimilar manufacturing is to create a therapeutic that is equivalent, but neither inferior nor superior, to the originator drug.

Along with equivalence, extrapolation is an important concept in biosimilars, Dr Cohen said. According to the US Food and Drug Administration (FDA), “A biosimilar may be approved in one or more indications for which the reference product is licensed based on the totality of evidence and with scientific justification.”

Extrapolation is not automatic for biosimilars, Dr Cohen noted. “The FDA requires clinical and scientific justification to extend approval to other indications that were not directly studied with the biosimilar.”

For example, he explained, clinical testing in a particular disease state may be required if there are questions about whether the biosimilar has the same mechanism of action, the same pharmacokinetics and biodistribution, different immunogenicity, or different toxicities. “The first biosimilars for infliximab weren’t approved for all the indications that the originator product was approved for, but recently, the FDA has approved one biosimilar for all those indications.”

The FDA has not yet allowed for interchangeability between originator compounds and biosimilars, Dr Cohen said, which means that the biosimilar may not be substituted for the reference product without the intervention of the healthcare provider prescribed the therapeutic.

The primary motivation to use biosimilars is cost savings, he said. “So far, efficacy and safety seem similar between originator drugs and biosimilars, and the cost savings substantial, in the range of 19% to 36%.”

The NOR-SWITCH study is perhaps the best-known trial involving changing patients with inflammatory bowel disease (IBD) from the originator compound—infliximab—to a biosimilar product. Dr Cohen explained that in this double-blinded study, adults who were stable on infliximab for 6 months were randomly assigned to be switched to a biosimilar or remain on the originator, and then followed for one year. Approximately 51% of the participants had IBD, he noted. Overall, the biosimilar, infliximab-dyyb, was shown to be noninferior to its originator in efficacy, trough drug levels, antibody rates, fecal calprotectin and c-reactive protein levels, and safety.

Additional studies are ongoing, including those involving multiple switches from originator to biosimilar and back to the originator. Dr Cohen referenced a study that showed that participants who underwent multiple switches over 3 years showed no differences in immunogenicity.

He emphasized, “Antidrug antibodies have been shown to cross-react between the originator biologic and the biosimilar, so the current paradigms for antidrug antibodies should apply—patients who develop neutralizing antibodies to the originator or to the biosimilar should not receive the other agent.”

Many questions remain unanswered, Dr Cohen stated, including one that will concern all gastroenterologists treating patients with IBD with biologics. “Will providers control what patients receive? Probably not, due to cost issues.”

—Rebecca Mashaw

Reference:

Cohen, RD. Framing the switch to biosimilars for patients and providers. Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; August 22, 2020; virtual.