The Biosimilar Void: 90% of Biologics Coming Off Patent Will Lack Biosimilars

A massive opportunity for cost savings remains untapped, as 90% of the 118 biologics losing exclusivity in the next decade—valued at $234 billion overall—currently have no biosimilars in development, according to a report from the IQVIA Institute for Human Data Science.¹

The report assessed patent expiries for all biologics in the US from 2025 to 2034 and examines factors that may hinder biosimilar development, including sales potential, patent timing, therapeutic area, orphan status, and molecular complexity.

Biosimilars have saved the US health care system $36 billion at invoice prices since the first biosimilar (Zarxio; filgrastim-sndz) launched in 2015. | Image credit: Luluraschi - stock.adobe.com

“Biosimilar competition provides cost savings and plays a vital role in the overall sustainability of the U.S. healthcare system. Understanding and addressing the biosimilar void is critical to realize the benefits these medicines bring,” wrote Murray Aitken, executive director of the IQVIA Institute for Human Data Science, in the report’s introduction.

In addition to the biologics preparing to lose exclusivity, of the 62 biologics currently not protected by patents, only 14 have biosimilars at the end of 2024, further limiting the potential biosimilars can save health institutions.

According to the past IQVIA data, biosimilars have already saved the US health care system $36 billion at invoice prices since the first biosimilar (Zarxio; filgrastim-sndz) launched in 2015.^2,3 Additionally, the US spent $324 billion on biologics in 2023, representing a whopping 45% of the US’ total drug expenditure.⁴ Between 2018 and 2023, invoice spending and volume for biologics increased by 15.3% and 8.5%, respectively, on average annually.

The authors emphasized the major opportunity that the next decade presents for biosimilars. On average, 12 biologics will lose exclusivity each year, exposing $23 billion in annual sales—more than double the rate of the past decade. Major expiries will occur in immunology and oncology, including multiple PD-1 inhibitors, which are key drivers of spending.

The Biosimilar Void

The report includes several references to “the biosimilar void,” referring to the 106 markets coming off patent by 2034 that do not currently have biosimilars in development.

To break down this gap further, of the biologics scheduled to lose exclusivity by 2034, 41% (n = 48) were considered to have high pre-expiry sales (generate at least $500 million in sales annually), of which only 23% have biosimilars in the pipeline. Similarly, nearly 60% of biologics set to lose exclusivity were considered lower-sales medicines (generate less than $500 million in sales annually), yet only 1 biologic from this category has a biosimilar in development (ramucirumab; Cyramza). Also, there is only 1 biosimilar candidate in development, for which the developer has not shared any clinical trial updates since 2022, suggesting the program may not continue.

“This lack of development in low-sales biologics represents a missed opportunity of nearly $9Bn in pre-expiry originator sales and over $156Bn including high-sales biologics with no biosimilar development. When taking a deeper look, biosimilar development is primarily targeting medicines expected to have greater than $1Bn in annual sales,” the authors explained.

Biosimilar development remains unlikely for low-sales biologics largely because of high development costs and a projected low return on investment, particularly for biologics used to treat rare disease with small patient populations, which represent 61% of the expiries through 2034. Even among high-sales biologics, 13 with near-term expiries have no biosimilars in development, suggesting additional factors influence manufacturer decisions.

Other Factors Affecting Development

Of the biologics with biosimilars in development, 92% of them are used in immunology and oncology. Although these markets also have the highest potential sales, other therapeutic areas, such as diabetes, neurology, and hematology, are left with limited biosimilar competition. Expanding biosimilar use in these areas may require additional education and support for specialists unfamiliar with biosimilars, which could further deter development.

The authors pointed to 5 main development challenges:

1. Regulatory Barriers: The US biosimilar approval pathway requires extensive studies to prove biosimilarity and interchangeability, adding cost and complexity. Also, US policies on interchangeability vary by state, unlike Europe’s uniform approach.
2. Market Acceptance: Uptake remains low due to originator strategies, payer controls, and provider preferences. Misconceptions about biosimilar safety and efficacy slow adoption.
3. High Investment Costs: Development costs range from $100 million to $250 million, making market entry risky. Companies have to recover expenses for clinical trials, manufacturing, and marketing.
4. Reimbursement Challenges: Pharmacy benefit managers and payers often favor originators due to rebate incentives. Limited formulary access can increase patient costs and discourage provider adoption.
5. Market Uncertainty: Biosimilar development takes years, during which new formulations or competing therapies may reduce demand. The Inflation Reduction Act’s Medicare price negotiations add further unpredictability, with 2 medications slated to face biosimilar competition within the decade being among the first chosen for price negotiations.⁵

There is particular concern for the rare disease space. Of the 118 biologics set to lose patent protection, 64% have orphan indications. However, only 1 biologic with only orphan indications, eculizumab, has biosimilars in development, and 88% of all expiring biologics with at least 1 orphan indication do not have biosimilars in the pipeline, creating difficulties in conducting clinical trials and recovering development costs, discouraging biosimilar manufacturers.

Complex biologics, such as antibody-drug conjugates, bispecific antibodies, cell therapies, and gene therapies, face even greater barriers to biosimilar competition. These therapies require high manufacturing investments, intricate logistics, and rigorous clinical testing. From 2025 to 2034, 16 complex biologics will lose patent protection, yet none currently have biosimilars in development. Despite their high costs, the limited market size and development challenges deter competition.

The authors warned, “As these complex biologics continue to represent an increasing share of biologic medicines, absent measures to overcome or offset the inherent challenges of bringing complex biosimilars to market will further limit the sustainability of the biosimilar market.

Addressing Ongoing Development Challenges

The report presented 3 potential solutions to better encourage biosimilar development in these underrepresented markets:

1. Regulatory streamlining
2. Collaboration
3. Improving market conditions

To create a sustainable biosimilar market, regulatory streamlining could ease development by reassessing clinical trial and interchangeability requirements. Improving market conditions through provider education, patient awareness, and financial incentives—like those in the Oncology Care Model—could boost biosimilar adoption. Addressing reimbursement challenges and fostering collaboration among stakeholders would further enhance access and cost savings. Proactive regulatory and market reforms will also be essential to maximizing biosimilars' impact on affordability and patient access.

The authors wrote, “To ensure the sustainability of the biosimilar market and that the savings and affordability benefits are fully realized by the healthcare system and patients, stakeholders must address the factors contributing to a biosimilar void.”

References

1. Assessing the biosimilar void in the U.S. IQVIA Institute for Human Data Science. February 2025. Accessed February 5, 2025. https://www.iqvia.com/Insights/The-IQVIA-Institute/Reports-and-Publications/Reports/Assessing-the-Biosimilar-Void-in-the-US

2. Jeremias S. Biosimilars account for 23% market share, with wide uptake disparities across molecules. The Center for Biosimilars^®. May 22, 2024. Accessed February 5, 2025. https://www.centerforbiosimilars.com/view/biosimilars-account-for-23-market-share-with-wide-uptake-disparities-across-molecules

3. Sandoz launches Zarxio^™️ (filgrastim-sndz), the first biosimilar in the United States. Press release. Sandoz; September 3, 2015. Accessed February 5, 2025. https://www.novartis.com/news/media-releases/sandoz-launches-zarxiotm-filgrastim-sndz-first-biosimilar-united-states

4. The U.S. generic & biosimilar medicines savings report: September 2024. AAM. September 6, 2024. Accessed February 5, 2025. https://accessiblemeds.org/sites/default/files/2024-09/AAM-2024-Generic-Biosimilar-Medicines-Savings-Report.pdf

5. Jeremias S. Stelara and Enbrel chosen for IRA price negotiation. The Center for Biosimilars. August 29, 2023. Accessed February 5, 2025. https://www.centerforbiosimilars.com/view/stelara-and-enbrel-chosen-for-ira-price-negotiation