Biosimilars Offer Opportunities to Improve Access and Outcomes for Patients With IMIDs

According to Jonathan Kay, MD, the US Food and Drug Administration (FDA) defines biosimilars as “highly similar to the reference product” with only “minor differences in clinically inactive components.” These therapeutics demonstrate “no clinical meaningful differences in safety, purity, and potency” to the originator products.

His own study of drug regulations in the US and aboard have led him to define a biosimilar drug as “a legitimate copy of a biopharmaceutical that is no longer protected by patent, which has undergone rigorous analytical and clinical assessment in comparison to the reference product and been approved by a regulatory agency in a highly regulated area according to a specific pathway.”

Dr Kay holds the Timothy S. and Elaine L. Peterson Chair in Rheumatology and is a professor of Medicine and Population and Quantitative Health Sciences at the UMass Chan Medical School in Worcester, Massachusetts.

Biologic therapies now account for almost half of the spending on medications globally, he said. “In 2019, the US spent $493 billion on medicines at manufacturer invoice prices, including $211 billion on biologics, which comprised 43% of total medicine spending,” Dr Kay explained. “Manufacturer net revenues for medicines, after discounts and rebates, totaled $356 billion, of which 48% were from sales of biologics.” Overall spending on biologics has grown significantly since 2014 at a compound annual growth rate of 14.6%, far outpacing the growth rate of 1.6% for small molecules.

Globally, the impact of biosimilars on the growth of spending could be substantial, he said, slowing the rate to 3% to 6% through 2027. Dr Kay commented that the savings realized could help make treatment accessible to patients from whom it has been out of reach financially and could also help facilitate the development of new drugs for unmet needs.

However, a number of misconceptions about biosimilars must be addressed with both clinicians and patients, to realize this potential, including that all commercial lots of biologic originator drugs are identical. This is not the case, Dr Kay explained. “All biologics are subject to variability; proven acceptable ranges (PARs) of variation are established during drug development and products are monitored to assure variation is within PARs.” Such changes may result from small modifications in the manufacturing process, or to the application of new technologies. “This does not pose safety or efficacy risk to patients,” he stressed.

In fact, Dr Kay said, switching from a reference product to a biosimilar is much the same as using a new batch or lot of an originator biologic, so such a switch should not result in a significant loss of efficacy or lead to increased adverse events or immunogenicity—another major misconception that can be countered by understanding the approval process for biosimilars. “Biosimilars have been shown to be highly similar to the reference product in extensive comparative analytical studies.”

FDA approves biosimilars through “a risk-based, totality-of-the-evidence approach to evaluate all available data and information submitted in support of the biosimilarity of the proposed product.” The agency determines the need for additional studies at each step in this progressive approach according to “the degree of residual uncertainty that remains at each step regarding the similarity of the products,” Dr Kay stated.

To date, he said, most if not all biosimilars have gone through the entire process from structural and functional characterization through nonclinical evaluation, human pharmacokinetic, pharmacodynamic, and immunogenicity studies, and additional trials. “No differences in safety or efficacy are expected between an approved biosimilar and its reference product,” Dr Kay stated.

Biosimilar approvals allow for extrapolation of indications: a trial in one disease may be used to support approval for other indications, he explained. Because clinical efficacy and safety have already been demonstrated by reference product, “there is no need to demonstrate efficacy of biosimilar in all indications.”

Legislation on substitution of biosimilars for reference products varies to some degree state by state, but any biosimilar product must be approved by the FDA first as a biosimilar and second as “interchangeable.” Some states require patient consent; in most cases the pharmacy must communicate with the prescriber about allowable substitution.

FDA guidance on demonstrating interchangeability states that biosimilars must conduct a prospective controlled switching study in which 2 groups of patients are treated first with the reference produce. Then the patients are randomized to 2 groups: one group is switched to the biosimilar while the other continues with the reference product. The switched group is then switched back to the originator and back again to the biosimilar, always ending with the biosimilar product. The groups’ responses are then compared according to specified endpoints.

Biosimilars have potential advantages to payers, providers, and patients, Dr Kay said. As more biosimilars are produced, the wider availability should decrease the cost of treating patients and introduce market competition, he said, causing manufacturers to offer discounts and rebates for the reference drug and driving the cost of the biosimilars down, as well. He noted that the average sales prices of originator infliximab has dropped 59% and that of the first biosimilar has gone down 74% since this biosimilar was introduced.

For providers, the lower costs should make these therapies more readily available to patients for whom the originator was inaccessible. In addition, Dr Kay said, “Biosimilars could receive preferred formulary status that could lessen burden of obtaining prior authorizations,” and these circumstances may allow for earlier access to biologics.

Dr Kay stressed, “Patients should also share in the direct savings that payers achieve” through the use of biosimilars.

To date the FDA has approved 40 biosimilar drugs, of which 29 are marketed. Seven adalimumab biosimilars and 2 for ustekinumab are expected to be on the market this year. “The incremental savings from biosimilars is projected to be $383 billion from this year through 2027.”

In working with patients, Dr Kay said, “I tell them that biosimilars are FDA approved and have been compared extensively to reference products and shown to be equal in efficacy and safety. I make the point that using these drugs is much using a different batch of reference product. I point out, as well, that the use of biosimilars benefits others by allowing more access to treatment due to lower costs, and that the savings may be redirected to pay for novel therapies for unmet needs.”

—Rebecca Mashaw

Reference:

Kay J. Biosimilars in the management of IMIDs: Opportunities to improve treatment access and outcomes. Presented at: Interdisciplinary Autoimmune Summit. April 26-28, 2023. Virtual.