Despite recent steps taken by the FDA to streamline approvals and increase availability for biosimilars, biosimilar adoption has been slow and primarily driven by payers in the United States, signaling that more needs to be done to encourage adoption, according to experts at a virtual workshop hosted by the FDA and the University of Maryland.
In April, the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) and the FDA jointly hosted a virtual workshop called “Biosimilars: A Decade of Experience and Future Directions – Strategies for Improving Biosimilar Adoption and the Potential Role of Clinical Pharmacology.” A summary was recently published in Clinical Pharmacology & Therapeutics, and the authors discussed the perspectives of academic clinicians who presented during the workshop on how to increase biosimilar adoption.
Despite recent steps taken by the FDA to streamline biosimilar approval and increase biosimilar availability, “biosimilar adoption in the United States has been slow and gradual, largely driven by payers rather than clinicians,” the authors wrote, adding that although biologics make up only 2% of prescriptions in the US, they represent 43% of invoice-level medicine spending.
Biosimilar Uptake by Therapeutic Area
The authors noted that biosimilar market share “varies widely” based on time on the market and the number of biosimilars in the product class, with market share ranging from 3% for insulin glargine to 89% for filgrastim as of September 2021.
Of the 35 biosimilars approved by the FDA at the time of the workshop, 19 were approved for oncology indications, including 11 cancer therapeutics (bevacizumab, rituximab, and trastuzumab) and 8 supportive care products (epoetin alfa, filgrastim, and pegfilgrastim). Biosimilar market share ranges between 38% and 89% for these products.
For rheumatology indications, adalimumab, etanercept, infliximab, and rituximab biosimilars have been approved by the FDA. However, the authors said “only a fraction” of these products are commercially available, and no adalimumab and etanercept biosimilars are available yet. Although “rheumatologists have been slow to prescribe biosimilars” referencing infliximab and rituximab, the authors said market share in rheumatology for these products has grown to approximately 32%.
For inflammatory bowel disease (IBD; Crohn disease and ulcerative colitis), biosimilars to the tumor necrosis factor alpha inhibitors infliximab and adalimumab have been approved. “However, all FDA-approved adalimumab biosimilars and one FDA-approved infliximab biosimilar have yet to launch,” the authors wrote, and similar to the situation in rheumatology, there has been “slow uptake” of infliximab biosimilars for treating IBD.
Insulin products were only recently transitioned to the regulatory pathway for biologics. Semglee, which received an interchangeability designation in July 2021, had 3% share of the insulin glargine market as of September 2021. Basaglar, approved in 2015 as a follow-on biologic, represents 44% of insulin glargine purchased under Medicaid.
Challenges to Biosimilar Adoption
The patent dance
One challenge identified by the academic clinicians presenting at the workshop was “the patent dance,” referring to patent infringement litigation initiated by the manufacturer of the reference product to delay the marketing of a recently approved biosimilar. Of the 35 biosimilars approved by the FDA, marketing of 10 was delayed by patent litigation.
Biosimilars for rheumatology indications have been “particularly affected” by these delays. For example, although adalimumab biosimilars have been available in most countries in Europe since 2018, the year the European patent for the reference product expired, in the United States where the primary patent expired in 2016, “the launch of adalimumab biosimilars is scheduled for 2023 due to a prolonged patent dance involving formulation and dosage patents.”
Prescribers’ concerns and unfamiliarity with the biosimilar paradigm
Workshop presentations cited “numerous surveys” that have documented the concerns of healthcare providers regarding biosimilars, “exposing the fact that physician and patient understanding of biosimilars remains insufficient,” the authors wrote.
Unlike originator biologics, biosimilars’ approval relies less on clinical data. According to the authors, concerns about the lack of clinical data “are likely impacting the uptake of the more recently approved cancer treatment biosimilars, which are not being adopted as rapidly and robustly as have been supportive care biosimilars,” especially among clinicians less familiar with the biosimilar paradigm and regulatory approval process. Similarly, many oncologists and gastroenterologists are reluctant to prescribe biosimilars that have been approved based on extrapolation from another indication.
Prescribers may also have concerns about drift. Unlike small molecule drugs, biosimilars may undergo multiple changes to their manufacturing process after initial approval, which could result in “drift,” changes in product quality attributes. Although proposed changes are reviewed by regulatory authorities for their potential impact on safety and efficacy, and manufacturers are expected to ensure batch-to-batch consistency, evidence of drift in the trastuzumab reference product caused concerns for oncologists, the authors said, and “biologics need to be closely monitored for potential drift.”
The prescribers presenting at the workshop also noted administrative hurdles to biosimilar adoption. The authors wrote, “many commercial payers list a preferred originator or biosimilar biologic product and require additional prior authorization steps for reimbursement of non-preferred formulary products.” Those extra steps create administrative burdens associated with using a non-preferred biosimilar product. They added that biosimilars are “more susceptible” to changes in formulary status than their originators.
Interchangeability and pharmacy-level substitution
According to the authors, some clinicians perceive the interchangeability designation for biosimilars as “an infringement upon the decision-making power of the provider.” However, these concerns “need to be nuanced by the fact that substitution at the pharmacy level for FDA-designated interchangeable products is regulated by state legislation in most of the United States.” They said that state laws “almost uniformly” require the pharmacist to notify both the provider and patient that a substitution has been made.
Lack of pricing incentive to prescribe biosimilars
Although biosimilars cost less for insurance providers, the authors said, those cost savings may not be passed down to patients. “Innovator companies negotiate substantial rebates with pharmacy benefit managers that often offset the difference between the listed prices of a biosimilar and its innovator counterpart.” They said this is particularly significant for biosimilar insulins and biosimilars for rheumatology indications.
Nocebo effect and lack of patient awareness
Unfamiliarity with biosimilars may cause negative expectations among patients about to switch from a reference product to a biosimilar, leading to poor clinical outcomes or adverse events due to the nocebo effect, followed by discontinuation of the biosimilar. Surveys have reported “low patient awareness and unfavorable perceptions of biosimilars,” the authors said, highlighting the need for patient education to improve biosimilar adoption.
Education, Integration of Biosimilars into Clinical Practice Guidelines, More Real-world Data Could Drive Biosimilar Adoption
The authors cited a 2018 survey of managed care and specialty pharmacy professionals asked to identify barriers to biosimilar adoption. The survey responses indicated that “many of the barriers identified as difficult to overcome could be addressed by education, including prescriber and patient concerns about biosimilar safety and efficacy.” The highest rated strategies to overcome these barriers were prescriber education about evidence from switching studies and FDA guidance on pharmacy-level substitution of originators with biosimilars. “These survey results suggest that education efforts undertaken by the FDA and clinical societies are impactful and should be continued,” the authors wrote.
They added that provider-driven patient education could also help to increase biosimilar adoption, as well as integration of biosimilars into practice guidelines from clinical societies. They noted that American Society of Clinical Oncology has incorporated biosimilars into their supportive care guidelines, and “integration of biosimilars into cancer treatment guidelines is underway.” Similarly, the American College of Rheumatology released a position statement encouraging clinicians to incorporate biosimilars into their practice.
Finally, they said, accumulation and increased availability of post-marketing surveillance and real-world data will help address prescriber concerns over extrapolation and switching.
Shubow S, Sun Q, Nguyen Phan AL, et al. Prescriber perspectives on biosimilar adoption and potential role of clinical pharmacology: a workshop summary. Clin Pharmacol Ther. October 17, 2022. Accessed December 14, 2022. doi:10.1002/cpt.2765