The American College of Rheumatology (ACR)'s previous position on biosimilars was one of caution during the initial development, evaluation, and approval of these drugs, but, writes the organization, “Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and as the [United States] is on the verge of a similar transition, the ACR is poised to reconsider its position.”
The American College of Rheumatology (ACR) has released a long-anticipated white paper, “The Science Behind Biosimilars: Entering a New Era of Biologic Therapy,” that encourages rheumatologists to use biosimilars in clinical practice. ACR’s previous position on biosimilars was one of caution during the initial development, evaluation, and approval of these drugs, but, writes the organization, “Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and as the [United States] is on the verge of a similar transition, the ACR is poised to reconsider its position.”
“The ACR has closely followed the development, evaluation, and approval processes for biosimilar agents, in addition to observing their successful use in other countries,” S. Louis Bridges Jr, MD, PhD, chair of the ACR’s Committee on Research and lead author of the paper, said in a statement. “We are now confident that providers can recommend biosimilars as a safe, effective, and affordable option to patients, where appropriate.”
The white paper outlines the approval pathway for biosimilar products and the FDA’s “totality of the evidence” approach to demonstrating biosimilarity, highlights the fact that product drift and evolution may occur even within originator biologics, underscores the need for post-marketing pharmacovigilance efforts, and describes the scientific basis for the extrapolation of indications in approved biosimilars.
The authors also differentiate important concepts related to using biosimilars in practice, including substitution of a biosimilar for a reference product. Substitution, write the authors, is the FDA-preferred term to describe a change made by someone other than the prescriber, such as a pharmacist, and is regulated by state law for biosimilars declared interchangeable by the FDA.
In contrast, nonmedical substitution (which the white paper also refers to as “payer substitution”) is a change “imposed on a medically stable patient for reasons unrelated to a drug’s efficacy or tolerability in a patient.” The authors point to insurance companies and pharmacy benefit managers (PBMs) as the drivers of nonmedical substitution, saying that such changes, which affect patient insurance coverage, are almost always made on the basis of cost.
The paper also addresses interchangeability, which is provided for under federal law. Under the biosimilar approval pathway, in order achieve an interchangeable designation—which no biosimilar manufacturer has yet sought or received for a biosimilar therapy—a product must be expected to produce the same clinical result as its reference in any given patient, and if administered more than once to a patient, the risk of developing an adverse event or experiencing diminished efficacy with alternating between the reference and the biosimilar must not be greater than the risk of using the reference product without interruption. In its draft guidance on demonstrating interchangeability, the authors note, the FDA proposes to rely on post-marketing pharmacovigilance data and data from at least 1 prospective, controlled switching study with a US-licensed reference drug.
The white paper also discusses “transitioning” or “changing” (referred to in federal law and in many clinical studies as “switching”) to a biosimilar, noting that a change in therapies is typically undertaken to reduce costs.
“We expect that transitioning and non-medical substitution will become as common in the [United States] as it has in Europe and the rest of the world,” write the authors. While ACR encourages thorough post-marketing surveillance of both biosimilars and their reference products, as the US market enters into an era of insurance and PBM-mandated formulary preferences, “Based on clinical trial and ‘real-world’ observational data on transitioning between reference products and biosimilars, and on our understanding of product drift, we do not expect that there will be issues regarding efficacy and safety.”
The white paper makes special note of the fact that biosimilars should bring about cost savings if they are to be used in the United States: “The only anticipated advantage of a biosimilar over its reference product is lower cost, since the 2 drugs should otherwise be therapeutically equivalent,” write the authors, adding that “The degree to which the availability of biosimilars in the [United States] will drive down the cost of biologic therapy, and who will benefit from any cost reductions, remain to be seen.”
ACR notes that the US system of PBM negotiation for formulary placement could actually drive the cost of biologics higher, as reference drug makers increase rebates to earn favorable formulary status. If reference sponsors can successfully bar biosimilars from formulary uptake, “there no longer would be pressure on reference product manufacturers to lower prices, and the cost of treating patients would increase.”
In order to incentivize the use of biosimilars, commercial and government insurance programs should consider harmonizing drug prices with patients’ out-of-pocket costs, says ACR, and CMS should address the lingering challenge of the Medicare Part D coverage gap that maintains, rather than reduces, patient cost-sharing on biosimilar drugs.
Despite these challenges, ACR says that it remains optimistic that the use of biosimilars can improve patient access to biologic agents in the United States, allowing for the continued delivery of high-quality healthcare at a lower cost.