Breaking Down Barriers: Why Biosimilars Face Resistance in the US Market

Through the recent introduction of 9 US Food and Drug Administration (FDA)-approved adalimumab (Humira) biosimilars, with more in the pipeline, the US is experiencing a biosimilar boom. These drugs represent an opportunity to deliver more treatment options at a potential discount compared with reference biologics.

On average, biosimilars cost about 50% less than the reference brand.¹ This reduction in costs can benefit both the healthcare system and patients, especially those whose out-of-pocket payments are based on a drug's list price.

Biosimilars also play a critical role in healthcare by introducing pre-market competition. Juliana Reed, MS, executive director of the Biosimilars Forum, explained to HCPLive that this is particularly significant when considering biologic medications, without competition, account for 40% of Medicare's drug costs despite only constituting 2% of its prescriptions.

“Now that biosimilars are coming to the market, we should be able to see that 40% of Medicare's cost with competition go down,” she said. “And when those costs go down, Medicare will have more money to spend on other medicines, new innovations, and new treatments for Medicare beneficiaries.”

Increased competition from biosimilars in the market can also potentially decrease overall healthcare system costs, redirecting resources to other healthcare areas.^2,3

Despite this influx, the adoption of biosimilars in the US has been unexpectedly slow. Factors including interchangeability designation, pharmacy benefit managers (PBMs) limiting access to the drugs, and a lack of knowledge and comfortability with biosimilars among providers and patients have made it difficult for biosimilars to flourish in the US market the way they have in many other parts of the world.

Addressing Safety and Efficacy Concerns

Prior to FDA approval, biosimilars must meet strict criteria, ensuring no clinically meaningful differences in safety and efficacy compared with the reference product. These drugs undergo extensive testing, and post-approval monitoring ensures continued safety and effectiveness.⁴

However, clinicians and patients regularly express hesitancy when making the decision to initiate treatment with a biosimilar.

To combat this, Russell D Cohen, MD, gastroenterologist and professor at University of Chicago Medicine, stressed the importance of education to increase the understanding among providers and patients of the scientific rigor behind the development of biosimilars, as well as the benefits of these drugs.

“With my patients, I explain that the potential side effects associated with biosimilars are similar to those associated with the reference biologic, so, generally, patients should not experience any change in dosage or treatment plan,” he said. “I also assure patients that the FDA carefully reviews studies of biosimilars to ensure there are no clinically meaningful differences in safety or effectiveness compared to the original biologic.”

He also stressed healthcare providers should consider the possible financial burden on patients when prescribing treatment. With an influx of lower-priced biosimilar options available, cost can now be a part of the discussion of care. The introduction of more biosimilars also has the potentional, through a redirection of funds, to enhance patient experiences through innovation, such as advancements in usability and pain reduction associated with injection devices. Educating patients about these direct and indirect advantages can aid in informed decision-making.

“FDA approval is the gold standard around the world,” Reed emphasized. “The FDA will not approve a biosimilar unless it is seen as safe and efficacious with the same clinical results in quality as its reference product.”

Challenges and Barriers to Access

Challenges exist in accessing biosimilars within the US healthcare system and providers often follow insurance preferences due to system complexities. Additional barriers arise from formulary restrictions and insurance coverage, making it challenging for HCPs to prescribe specific biosimilars.

Interchangeability

In the US, interchangeability allows pharmacists to substitute biosimilars for the originator without prescriber permission. An interchangeable designation requires additional switching studies, ensuring the same clinical outcomes upon interchange and was initially designed to simplify access and accelerate medication availability.

However, this designation has been under scrutiny, as demonstrated by the recent FDA draft guidance recommending to remove it from the product’s prescribing information.⁵

“Part of the reason for that new recommendation is that we know an interchangeability designation does not mean one biosimilar is better or more biosimilar than another,” Jessica Ooman, PharmD, vice president of Medical Affairs for the US biopharmaceuticals team at Fresenius Kabi told HCPLive. “That's all proven through pharmacokinetics, analytical assessments, and clinical trials. It basically just means a particular company chose to do an additional study that required multiple switches between that particular biosimilar as well as the reference product.”

Understanding this definition is crucial as the biggest concern expressed by providers is the safety of switching between a biologic and biosmiliar, although data and experiences globally support the safety of switching without negative outcomes.Additional issues surrounding branding differences and misconceptions about quality necessitate robust education and support.

“A lack of education and exposure can heighten the nocebo response,” Gasteiger noted. “Confidence from healthcare providers, transparent education, and the continuity of patient support will be critical in these moments.”

The Role of PMBs

Another concerning aspect is the limited market access to biosimilars due to blockades from PBMs. This obstruction prevents cost-saving competition and inhibits patients from accessing lower-cost medicines, causing financial hardship. Such limitations might discourage future investment in biosimilar development, raising questions about the sustainability of the biosimilars market long-term.

“PBMs are making clinical decisions about the access to medicines and to lower cost medicines that should be between the patient and the physician,” Reed explained. “[Adalimumab is] a very expensive medicine and patients, if they had access to the adalimumab biosimilars, could be saving 85%. That's how big the discounts are.”

The emphasis remains on pressing PBMs to prioritize lowering costs through competition rather than relying solely on rebates. Collaboration among stakeholders is essential for realizing the potential benefits of biosimilars in the healthcare landscape.

The Clinician and Patient Perspective

Although the adoption of biosimilars has been slower than anticipated in the US, they have long been established internationally. Despite this familiarity, prescriber confidence and knowledge gaps are still present outside the US, leading to uncertainty and misinformation. Brand changes can disrupt patient care, which can lead to discontinuation and nocebo effects.⁶

Chiara Gasteiger, PhD, postdoctoral scholar in the Mind & Body Lab at Stanford University, and her team explored the experiences of 117 rheumatology patients and 164 healthcare providers regarding a mandated nationwide transition adalimumab biosimilar in New Zealand.⁷

“Patients reported low satisfaction with the support and information they received from patient support organizations, a lack of training for the device, and issues with the changes in care supplies and patient support program,” Gasteiger told HCPLive. “Similarly, providers (rheumatologists, rheumatology nurses and pharmacists) experienced an increased workload and were unsatisfied with the training for the biosimilar device and the information they received from government agencies.”

Gasteiger noted similar results from a cross-sectional study conducted in the UK, which examined the perceptions and experiences of patients switching from the biologic to an adalimumab biosimilar. Many patients were unsatisfied post-switch, underscoring the importance of communication, shared decision-making, training with the new device, and educational information to maximize treatment outcomes.⁸

Improving biosimilar acceptance requires an international collaborative approach and enhanced education.

The Future of Biosimilars in the US

The introduction of the adalimumab biosimilars brought attention to the functioning of our healthcare system. Contrary to expectations, the adoption of adalimumab biosimilars in the US market has not been as rapid as anticipated.

This discrepancy has prompted Congress to scrutinize existing policies, with a growing interest in understanding why other countries have successfully transitioned to biosimilars, resulting in significant healthcare cost savings, while the US lags behind. This has prompted policymakers to reassess structures, including formularies, insurer roles, and healthcare delivery mechanisms, aiming to ensure the anticipated cost savings from biosimilars become a reality.

“If stakeholders, including the PBMs, support biosimilar uptake and demand patients have access to competition and lower costs, I think the biosimilars industry could be robust,” Reed said.

As healthcare systems gain experience, Gasteiger believes there will be increased confidence, streamlined regulatory processes, and improved administrative efficiency for healthcare providers, and the biosimilars market will continue to expand.

“A lot of the conditions that these biosimilars treats can cause permanent life changing outcomes or irreversible damage,” Ooman stated. “With biosimilars, the hope is that they can get these medications sooner and it is easier for the healthcare providers to have access to them as well.”

Biosimilars offer a significant opportunity in healthcare by providing life-changing medications to patients in need. Ultimately, the goal is to make biosimilars more accessible to patients and healthcare providers, aligning with their potential to positively impact patients' lives. Continued progress in this direction will allow patients to receive these treatments when needed, reducing the burden of chronic diseases, and improving their quality of life.

References

1. ^{Association for Accessible Medicines. (September 2022). The US Generic & Biosimilar Medicines Savings Report. Accessed December 13, 2023. https://accessiblemeds.org/sites/default/files/2022-09/AAM-2022-Generic-Biosimilar-Medicines-Savings-Report.pdf}
2. ^{Aitken M, Kleinrock M, Pritchett J. Biosimilars in the United States 2023-2027: competition, savings, and sustainability. IQVIA Institute for Human Data Science. January 31, 2023. Accessed December 13, 2023. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2023-2027}
3. ^{Aitken M, Mugele D, Newton M, Rodríguez I, Vázquez M. Spotlight on Biosimilars. IQVIA Institute for Human Data Science. June 2021. Accessed December 13, 2023. https://www.iqvia.com/insights/the-iqvia-institute/reports/spotlight-on-biosimilars}
4. ^{Biosimilar basics for patients. US Food and Drug Administration. March 21, 2023. Accessed December 13, 2023. https://www.fda.gov/drugs/biosimilars/biosimilar-basics-patients}
5. ^{Center for Drug Evaluation and Research. (2023, September 18). Labeling for Biosimilar and Interchangeable Biosimilar Products. US Food and Drug Administration . https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-biosimilar-and-interchangeable-biosimilar-products}
6. ^{Sarnola K, Merikoski M, Jyrkkä J, Hämeen-Anttila K. Physicians' perceptions of the uptake of biosimilars: a systematic review. BMJ Open. 2020;10(5):e034183. Published 2020 May 5. doi:10.1136/bmjopen-2019-034183}
7. ^{Gasteiger C, Lobo M, Stanley R, Wong LS, Murdoch R, Dalbeth N. Rheumatology Patients' Experiences of a Mandatory Nationwide Transition to an Adalimumab Biosimilar. ACR Open Rheumatol. Published online November 23, 2023. doi:10.1002/acr2.11634}
8. ^{Kaneko K, Prieto-Alhambra D, Jacklin C, et al. Influence of information provided prior to switching from Humira to biosimilar adalimumab on UK patients' satisfaction: a cross-sectional survey by patient organisations. BMJ Open. 2022;12(2):e050949. Published 2022 Feb 16. doi:10.1136/bmjopen-2021-050949}