Sophia Z. Humphreys, PharmD, MHA, BCBBS, of Sutter Health in Sacramento, California, details the regulatory decisions from 2022, what's to come in 2023, and how the US biosimilars market is expected to shift over the next 5 years.
In recent years, specialty medication spending has increased significantly. For the United States, in 2021, specialty medications accounted for 55% of the total spending for prescription medications.1 Most of these specialty medications are large molecule biologics. In 2019, these large molecule biologic medications represented 43% of all invoice-level medication spending in the United States, reaching $211 billion.
Thus, control of biologic spending is an important key to reducing drug costs. This can be accomplished through greater utilization of biosimilars. Biosimilars are highly similar to high-cost biologics, with no meaningful clinical differences. They are marketed at a significantly lower price and, therefore, can contribute to significant savings. In 2021, the savings achieved by using biosimilars exceeded $10 Billion in United States.1
Biosimilar research and development have been exceedingly active in recent years. As a result, as many as 106 biosimilars are currently under development. Biosimilar development is expanding outside of cancer care medications into new therapeutic classes such as ophthalmology, bone health and immunosuppressants.
Cancer curative and supportive biosimilars have been very successful. There will be even more competition in these therapeutic classes in the new year. Three biosimilars to cancer supportive care biologics were approved by the FDA in 2022, and their US launches are expected in 2023. They are Releuko (filgrastim-ayow), Fylnetra (pegfilgrastim-pbbk), and Stimufend (pegfilgrastim-fpgk).
More biosimilars to Neupogen (filgrastim) and Neulasta (pegfilgrastim) are in the pipeline from multiple manufacturers in 2023 and beyond. Biosimilars to the 3 curative biologics, Avastin (bevacizumab), Herceptin (trastuzumab), and Rituxan (rituximab) have experienced great success in the past 3 years. They will face more competition from newer biosimilars in the pipeline from multiple manufacturers soon. There are more than 4 biosimilars in the pipeline for all 3 molecules (6 for Avastin, 5 for Herceptin, and 4 for Rituxan).
Autoimmune agents have surpassed oncology medications in spend and growth rate. From 2011 to 2021, the spending on autoimmune medications increased 459%, while spending on oncology medications increased 226%. Total spend of autoimmune agents exceeded $42 billion dollars in the past 5 years in United States.1 Humira (adalimumab) is the top-selling autoimmune biologic. Humira accounted for $20.7 billion in sales globally in 2021. Thus, the new biosimilars to Humira are expected to bring sizable savings to health care systems.2023 marks the first year that biosimilars of Humira are finally reaching the US market.
It has been 6 years since the first biosimilar to Humira was approved by the FDA in 2016. However, litigations and settlement discussions have delayed the product launch until this year. Amgen’s Amjevita (adalimumab-atto) is expected to be available in the United States as early as January 2023. Multiple biosimilars to Humira have been launched in the European Union since 2018, but with 83.7% of the total global purchase of Humira coming from the United States, the 2023 US biosimilar launch will have the highest impact on Humira sale.2 As with all other reference products with biosimilars available, we anticipate price competition to drive down both the prices for biosimilars and the reference product.
After the December 2022 approval of Idacio (adalimumab-aacf) by Fresenius Kabi, there are now a total of 8 biosimilars to Humira in the United States. They are: Yusimry (adalimumab-aqvh) by Coherus BioSciences, approved in December 2021; Hulio (adalimumab-fkjp) by Viatris/Fujifilm Kyowa Kirin, approved in July 2020; Abrilada (adalimumab-afzb) by Pfizer, approved in November 2019; Hadlima (adalimumab-bwwd) by Organon/Samsung Bioepis, approved in July 2019; Hyrimoz (adalimumab-adaz) by Sandoz, approved in October 2018; Cyltezo (adalimumab-adbm) by Boehringer Ingelheim, approved in August 2017 and Amjevita, approved in September 2016. All are expected to launch in 2023. Five more are in various stages of development. The biosimilar market for Humira is going to be more competitive than all previous biosimilar launches.3
Humira biosimilars are unique because they are the first pharmacy benefit non-insulin biosimilars launched in the United States. All non-insulin biosimilars that have been released to the US market thus far are clinic administered and reimbursed under medical benefit. Therefore, large health systems have relative control. They can decide which biosimilars to add to their formulary, negotiate with both reference product and biosimilar manufactures for best contract terms, and build system preferred biosimilars in their Electronic Health Recordsystem in ways which encourage the physicians to prescribe the health system preferred biosimilars.4
Humira, however, is largely dispensed in the retail pharmacies and reimbursed at the pharmacy level. This presents new challenges to formulary managers in the health systems. The reference product will almost certainly reduce its price and make Humira more competitive this year. Since each biosimilar is reimbursed based on its own average sales price (ASP), the biosimilar manufacturers have a balancing act to perform. On one hand, they must keep the biosimilars’ ASP high enough for a reasonable reimbursement. On the other hand, they need to offer a price lower than Humira and other biosimilars to satisfy the pharmacies and health systems. Not all payers will cover all 8 biosimilars, so each manufacturer would have to consider balancing rebates to attract the payers and pharmacy benefit managers.4
The pipeline of tumor necrosis factor inhibitors’ biosimilar development is also active. Stelara (ustekinumab) is the next autoimmune biologic to lose exclusivity in 2023. There is no FDA-approved biosimilar to Stelara yet, but 9 biosimilars are in various stages of development with 2 pending FDA approval in 2023. Following Stelara, Simponi (golimumab) and Cimzia (certolizumab pegol) will both lose their exclusivity in 2024. The development of biosimilars to both molecules are underway. Potential launches are expected in 2024.4
Enbrel’s extended exclusivity pushed biosimilar launch to 2029, even though 2 biosimilars to Enbrel (etanecept) have been approved by the FDA. Erelzi (etanercept-szzs) of Sandoz was approved in 2016, and Eticovo (etanercept-ykro) by Samsung Bioepis was approved in 2019. Lupin and Protheragen are both developing new biosimilars to Enbrel.5
The long awaited biosimilars to Actemra (tocilizumab) are also near launch. Both Fresenius and Bio-Thera/Biogen are expected to seek FDA approval for their biosimilars to Actemra in 2023. Celltrion and Mycenax-Gedeon are expected to seek FDA approval for their biosimilars to Enbrel within the next 3 to 5 years. Xolair (omalizumab) will face biosimilar competition soon after 2024 with both Teva and Celltrion’s biosimilar candidates in phase 3 trials. Tysabri (natalizumab) will not loss exclusivity until 2026, but Sandoz-Polpharma already have a biosimilar pending FDA approval.5
Novolog (insulin aspart) will face biosimilar competition from Mylan, Sanofi, and Amphastar in the next few years. All 3 companies have biosimilars to Novolog in development, and all are seeking interchangeability designation. Long-acting insulin, Lantus (insulin glargine) will also face more biosimilar competition in addition to the 2 biosimilar on the US market now: Semglee (insulin glargine-yfgn) and Rezvoglar (insulin glargine-aglr).3
Ophthalmology agents saw biosimilar competition for the first time in 2022. There are 2 biosimilars to Lucentis (ranibizumab) available in the United States.Byooviz (ranibizumab-nuna) by Biogen was launched in July 2022. The interchangeable biosimilar by Coherus Biosciences, Cimerli (ranibizumab-eqrn), was launched in October 2022.
The interchangeable biosimilar to Lucentis is expected to bring more competition, because many states allow automatic pharmacy level switching from reference product to the interchangeable biosimilars without the authorization of the physician who prescribed the reference product.4 Two more biosimilars to Lucentis are in phase 3 trials and expected to seek approval within the next 2 years. As least 9 biosimilars to Elyea (aflibercept) are in various stages of development. The first approval of Elyea biosimilar is expected in 2023.3
Amgen’s receptor activator of nuclear factor kappa-B ligand inhibitor Prolia/Xgeva (denosumab) is going to lose its exclusivity by February 2025. Nine biosimilars to reference denosumab are in phase 3 trials.5 Soloris (eculizumab) will also loss exclusivity in 2025, and 2 biosimilars are in development when this report was written in January 2023.6
Overall, although the acceptance of biosimilars in the United States is relatively slow compared to the European Union, the pace is increasing. This trend is expected to continue, with a projected savings of up to $133 billion through US biosimilar use by 2025.7 The launch of biosimilars and their utilization in United States health care facilities have reduced biologic medications spend 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.4 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 to enhance health care industry post COVID-19 financial recovery.
Sophia Z. Humphreys, PharmD, MHA, BCBBS, is the director of system pharmacy formulary management & clinical programs at Sutter Health in Sacramento, California. She has nearly 20 years of specialized experience in the pharmaceutical industry and is an expert in pharmacy regulatory compliance, US Pharmacopeia General Chapter <797>/<800> pharmacy regulations, clinical education, long-term care pharmacy service, and pharmaceutical waste management. She has a strong background in strategic planning and project management. Prior to her current position, she served as the director of system pharmacy clinical services at Providence St. Joseph Health.