Biosimilar Market Outlook Looks Strong

In recent years, specialty medication spending has significantly increased. Specialty medications accounted for 55% of total prescription medication spending in 2021 in the United States.¹ Most specialty medications are large molecule biologics. In 2019, biologic medications represented 43% of all invoice-level medicine spending in the United States, reaching $211 billion.² Thus, controlling biologic spending is the key to reducing drug costs for the health care industry.

Biosimilars are similar to these high-cost biologics, with no meaningful clinical differences, and they are marketed at a significantly lower price compared with brand-name biologics. Biosimilars contribute to significant savings and have been exceedingly active in recent years. As many as 106 biosimilars are under development, encompassing not only cancer care medications but also new therapeutic classes such as bone health, immunosuppressants, and ophthalmology.³

Cancer curative and supportive biosimilars have been phenomenally successful, so there will naturally be more competition in these therapeutic classes. Three biosimilars to cancer supportive care biologics were approved in 2022, and launches are expected in 2023. These include pegfilgrastim-pbbk (Fylnetra), filgrastim-ayow (Releuko), and pegfilgrastim-fpgk (Stimufend). More biosimilars of pegfilgrastim (Neulasta) and filgrastim (Neupogen) are in the pipeline from multiple manufacturers. Biosimilars to the 3 curative biologics—bevacizumab (Avastin), trastuzumab (Herceptin), and rituximab (Rituxan)—have experienced remarkable success in the past 3 years and will soon face more competition from newer biosimilars in the pipeline from multiple manufacturers. There are more than 4 biosimilars in the pipeline for all 3 molecules: 6 for bevacizumab, 5 for trastuzumab, and 4 for rituximab.

Autoimmune agents have surpassed oncology medications in terms of both the spending and the growth rate. Between 2011 and 2021, spending on autoimmune medications increased 459%, whereas spending on oncology medications increased less than half that rate, at 226%. Total spending onautoimmune agents exceeded $42 billion in the past 5 years in United States.¹ Adalimumab (Humira) is the top-selling autoimmune biologic. Brand-name Humira accounted for $20.7 billion in sales globally in 2021.² Thus, the new adalimumab biosimilars are expected to bring sizable savings.

This year marks the first time that adalimumab biosimilars are reaching patients in the United States. It has been 6 years since the FDA approved the first adalimumab biosimilar in 2016; however, litigation and settlement discussions have delayed the first launch until 2023. Adalimumab-atto (Amjevita; Amgen) is expected to be the first adalimumab biosimilar to come to the US market in January 2023.² Multiple adalimumab biosimilars have been launched in the European Union since 2018.3 However, with 83.7% of the total global purchase of adalimumab coming from the United States, the 2023 biosimilar launch will make the biggest impact on brand-name Humira sales.⁴ As with other reference products that have biosimilars available in the US market, price competition will likely drive down both the biosimilars’ and the brand-name reference products’ prices.

After the December 2022 approval of adalimumab-aacf (Idacio; Fresenius Kabi), there are now 8 adalimumab biosimilars that are approved by the FDA.⁵ These include adalimumab-aqvh (Yusimry; Coherus BioSciences, Inc), approved in December 2021; adalimumab-fkjp (Hulio; Viatris Inc/Fujifilm Kyowa Kirin Biologics Co, Ltd), approved in July 2020; adalimumab-afzb (Abrilada; Pfizer Inc), approved in November 2019; adalimumab-bwwd (Hadlima; Organon/Samsung Bioepis Co, Ltd), approved in July 2019; adalimumab-adaz (Hyrimoz; Sandoz), approved in October 2018; adalimumab-adbm (Cyltezo; Boehringer Ingelheim), approved in August 2017; and adalimumab-atto by Amgen, approved in September 2016.⁴ All are expected to launch in 2023, and 5 more biosimilars are in various stages of development. The market will be the most crowded for biosimilars to date.⁶

Adalimumab biosimilars are unique because they are the first pharmacy benefit noninsulin biosimilars launched in the United States. All noninsulin biosimilars that have been released to the US market thus far are clinically administered and are reimbursed under Medicare Part B. Therefore, large health systems have relative control. They can decide which biosimilars to add to the formulary, negotiate with both reference product and biosimilar manufacturers for best contract terms, and build system-preferred biosimilars in their electronic health record system in ways that guide physicians to prescribe the health system–preferred biosimilars.

However, adalimumab is largely dispensed in retail pharmacies and is reimbursed at the pharmacy level (ie, Medicare Part D), which presents new challenges to formulary and utilization managers in the health systems. The reference product will almost certainly reduce its price and make brand-name Humira more competitive next year. Because each biosimilar is reimbursed based on its own average sales price (ASP), the manufacturers must perform a balancing act. On one hand, they must keep the biosimilars’ ASP high enough for a reasonable reimbursement. On the other hand, they must offer a price that is lower than brand-name Humira and other biosimilars to satisfy health systems and pharmacies. Not all payers will cover 8 adalimumab biosimilars, so each manufacturer would have to consider balancing rebates to attract payers and pharmacybenefit managers.

The pipeline of tumor necrosis factor inhibitors’ biosimilar development is also active. Ustekinumab (Stelara) is the next autoimmune biologic to lose its exclusivity in 2023. There is no FDA-approved ustekinumab biosimilar yet, but 9 biosimilars are in various stages of development, with 2 pending FDA approvals in 2023. Following ustekinumab, certolizumab pegol (Cimzia) and golimumab (Simponi) will both lose their exclusivity in 2024. The development of biosimilars to both molecules are underway, and potential launches are expected in 2024. Extended exclusivity for etanercept (Enbrel) pushed biosimilar launch to 2029, even though the FDA has approved 2 etanercept biosimilars: etanercept-szzs (Erelzi; Sandoz) was approved in 2016, and etanercept-ykro (Eticovo; Samsung Bioepis Co, Ltd) was approved in 2019. Lupin Limited and Protheragen are both developing etanercept biosimilars.⁷

The long-awaited Actemra (tocilizumab) biosimilars are also nearing launch. Biogen Inc, Bio-Thera Solutions, Ltd, and Fresenius are expected to seek FDA approval for their tocilizumab biosimilars in 2023. Celltrion, Mycenax Biotech Inc, and Gedeon Richter Plc are expected to seek FDA approval for their etanercept biosimilars within the next 3 to 5 years. Xolair (omali-zumab) will face biosimilar competition soon after 2024, with both Celltrion and Teva Pharmaceuticals’ biosimilar candidates in phase 3 trials. Tysabri(natalizumab) will not lose exclusivity until 2027, but Sandoz and Polpharma Biologics already have a biosimilar that is pending FDA approval.

Insulin aspart (Novolog) will face biosimilar competition from Amphastar Pharmaceuticals, Inc, Mylan NV, and Sanofi in the next few years, as all 3 companies have insulin aspart biosimilars in development and are seeking interchangeability designation. Insulin glargine (Lantus) will also face more biosimilar competition in the pipeline in addition to the 2 biosimilars in the US market: insulin glargine-aglr (Rezvoglar) and insulin glargine-yfgn (Semglee).

Ophthalmology agents saw biosimilar competition for the first time in 2022. There are 2 Lucentis (ranibizumab) biosimilars available in the United States: ranibizumab-nuna (Byooviz; Biogen Inc) was launched in July 2022, and the interchangeable biosimilar, ranibizumab-eqrn (Cimerli; Coherus BioSciences, Inc), was launched in October 2022. The interchangeable ranibizumab biosimilar is expected to bring more competition, as many states allow automatic pharmacy-level switching from the reference product (ranibizumab) to the interchangeable biosimilars without the authorization of the physician who prescribed the reference product. Two more ranibizumab biosimilars are in phase 3 trials and are expected to seek approval within the next 2 years. At least 9 Eylea (aflibercept) biosimilars are in various stages of development. The first approval of an aflibercept biosimilar is expected in 2023.

Amgen’s receptor activator of nuclear factor kappa B ligand inhibitor denosumab (Prolia and Xgeva) will lose its exclusivity by February 2025. Nine denosumab biosimilars are in phase 3 trials. Eculizumab (Soliris) will also lose exclusivity in 2025, and 2 biosimilars were in development as of press time.⁸

Overall, though the acceptance of biosimilars in the United States is relatively slow compared with the European Union, the pace is increasing. This trend is expected to continue, with a projected savings of up to $133 billion through biosimilar use in the United States by 2025. The launch of biosimilars and their use in US health care facilities has reduced biologic medications spending and improved overall health system financial sustainability. The resulting cost savings and the increased access to care are expected to help improve overall population health outcome. The financial benefits and treatment accessibility these products offer may play a significant role in optimizing affordable access to critical biologic medications.⁹ Health system pharmacy leaders should develop and implement innovative, multidisciplinary biosimilar utilization programs to improve the adoption of biosimilars to increase financial sustainability and help enhance the health care industry’s financial recovery post COVID-19.

References

1. The use of medicines in the U.S. 2022: usage and spending trends and outlook to 2026. IQVIA. April 21, 2022. Accessed December 28, 2022. https://www.iqvia.com/insights/the-iqvia-institute/reports/the-use-of-medicines-in-the-us-2022

2. 2022 biosimilar trends report. Amgen. Accessed December 28, 2022. https://www.amgenbiosimilars.com/commitment/2022-Biosimilar-Trends-Report

3. Hargreaves B. First wave of Humira biosimilars enters EU market. BioPharma-Reporter.com. October 16, 2018. Accessed December 29, 2022. https://www.biopharma-reporter.com/Article/2018/10/16/First-wave-of-Humira-biosimilars-enters-EU-market?utm_source=copyright&utm_medium=On-Site&utm_campaign=copyright

4. 2021 annual report on Form 10-K. AbbVie. Accessed July 31, 2022. https://investors.abbvie.com/static-files/91cf9d6a-8e6f-4059-9575-eda83b7e4623

5. Biosimilar product information. FDA. December 19, 2022. Accessed January 4, 2022. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information

6. Patel U. The coming wave of biosimilar medications. Evernorth Health Services. June 15, 2021. Accessed January 4, 2022. https://www.evernorth.com/articles/the-coming-wave-of-biosimilar-medications

7. Merrill J. The next big patent cliff is coming, and time is running out to pad the fall. Scrip Pharma Intelligence. April 4, 2022. Accessed December 30, 2022. https://scrip.pharmaintelligence.informa.com/SC146175/The-Next-Big-Patent-Cliff-Is-Coming-And-Time-Is-Running-Out-To-Pad-The-Fall

8. Alexion delays Soliris biosimilar until 2025. Generics and Biosimilars Initiative. August 28, 2020. Accessed January 2, 2023. https://www.gabionline.net/policies-legislation/Alexion-delays-Soliris-biosimilar-until-2025

9. Humphreys SZ. Real-world evidence of a successful biosimilar adoption program. Future Oncol. 2022;18(16):1997-2006. doi:10.2217/fon-2021-1584

About the Author

Sophia Z. Humphreys, PharmD, MHA, BCBBS, is the director of system pharmacy clinical programs and formulary management at Sutter Health in Sacramento, California.