In recent years, the evolving landscape of biosimilars has helped flood the market with a huge amount of information. In dermatology, biosimilars approvals have been pending since 2016 for adalimumab, a tumor necrosis factor inhibitor used to treat moderate to severe plaque psoriasis and hidradenitis suppurativa (HS); however, the former was only recently launched. Adalimumab-atto (Amjevita; Amgen) hit the market on January 31, 2023 and has exclusivity until July 2023. Potentially eight to ten additional biosimilars of adalimumab will be launched between July and December 2023.1
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In March 2010, the Biologics Price Competition and Innovation Act, as part of the Affordable Care Act, included a standardized approval pathway for biologics, biosimilar and interchangeable products. After a 10-year transition period, biosimilar products must now be approved with an organic license application.1 This shortened approval path for biosimilars does not routinely require clinical trials to re-establish efficacy and safety such as the comprehensive new drug applications that were previously required. Instead, the manufacturer must demonstrate that the proposed product is biosimilar to an FDA-approved reference product using comparative tests of safety, purity, and potency.2-5 Adalimumab’s approved biosimilars have consistently demonstrated these qualifications in clinical studies.6
Biosimilars cannot be automatically substituted for a pharmacist-level reference product without prescriber approval, unless the biosimilar has been granted interchangeability status (subject to state laws).7 Switchover studies shall be conducted for interchangeable products to demonstrate that switching from the proposed product to the reference product does not increase the safety risks or decrease efficacy compared to using the reference product without switching. If a product is initially approved as a biosimilar, it may subsequently be approved as an interchangeable subject to a supplemental application that addresses interchangeability standards.8 There is currently 1 interchangeable biosimilar of adalimumab, adalimumab-adbm (Cyltezo; Boehringer Ingelheim), which has been approved in August 2017 and received interchangeability designation in October 2021. Adalimumab-adbm is expected to be launched in July 2023, with market exclusivity of interchangeability maintained for approximately 1 year.9
Following FDA approval, differences in the biosimilar products’ concentration, preservative content, package size, and commercially available device from the reference products are permitted; this is of particular interest for the biosimilars adalimumab. Adalimumab (Humira; AbbVie) is currently available in a high-strength (40 mg/0.4 mL), citrate-free formulation, as well as the original strength (40 mg/0.8 mL), which contains citrate; both are commercially available in a prefilled syringe or an autoinjector. Currently, the majority of adalimumab use is in the high-strength formulation. The biosimilars scheduled to be launched in July 2023 include both highly concentrated and original formulations. The biosimilar adalimumab-act is available as a pre-filled syringe without citrate or an auto-injector, with a strength of 40 mg/0.8 mL, which is the stock strength.10.11 Adalimumab is commonly prescribed and first dispensed in a 3-pack autoinjector starter kit for both plaque psoriasis and HS, whereas adalimumab-atto does not have this option.11.12 For this reason, such differences in packaging can present potential points of confusion for the provider, pharmacy, and patient.
A reference product may have unexpired exclusivity for a particular indication which prevents biosimilar manufacturers from obtaining approval for that indication. Therefore, a biosimilar could be approved with fewer indications than the reference product; this is termed a lean label. In this way, biosimilars do not automatically adopt all previously patented indications when the patents of the reference products expire. Each biosimilar sponsor may submit additional applications to obtain approval for additional indications when the reference product’s patent expires.1.14pm
For example, the orphan drug exclusivity (ODE) patent for adalimumab for HS expired on September 9, 2022. Adalimumab-act and adalimumab-adbm were not initially approved under the HS indication, but this was added as an indication for both products in March 2023. The adolescent HS indication is protected by ODE until October 16, 2025, after which time any biosimilar sponsor can apply for approval.9,11,15
The launch of biosimilars increases competition for the reference product and introduces opportunities for price reductions. The projected market share of adalimumab biosimilars remains unknown, as negotiations between the benefits manager and the pharmaceutical payer continue to delay immediate market impact.16 There is currently no incentive to switch patients from the reference product adalimumab to a biosimilar product. However, in response to anticipated biosimilar launches starting in July 2023, payers may start preferring certain products through a tiered form.
Patient preference and out-of-pocket costs may also become a factor when considering co-pay programs offered by individual biosimilar manufacturers. Adalimumab will likely remain preferred over most formularies in 2023 and a high percentage of formularies in 2024.17
AbbVie has reached licensing and transaction agreements with several biosimilar sponsors; however, it may come under pressure to provide significant discounts to maintain its market share. Ustekinumab (Stelara; Janssen Biotech, Inc) will be the next commonly prescribed biologic drug in dermatology to lose its patent exclusivity, in September 2023, with biosimilars expected to launch between 2023 and 2025.18
Going forward, it is likely that the adoption of biosimilars in clinical practice will remain somewhat dependent on prescriber inertia, tiered formulary adjustments and patient preferences. However, that may gradually begin to blur the status quo as more options become available to the market.
References
1. Bhat S, Patel M, Duly K, Choi D. Adalimumab-adbm: the first interchangeable biosimilar for the treatment of inflammatory diseases. Ann Pharmacother. 2022;56(12):1356-1364. doi:10.1177/10600280221082196
2. Schiestl M, Ranganna G, Watson K, et al. The path to tailored biosimilar clinical development. Biopharmaceuticals. 2020;34(3):297-306. doi:10.1007/s40259-020-00422-1
3. White J, Goldman J. Biosimilar and follow-on insulin: the details, disadvantages, and interchangeability. J Pharma Technol. 2019;35(1):25-35. doi:10.1177/8755122518802268
4. Zhang RM, Puri R, McGill JB. Update on biosimilar insulins: a US perspective. Biopharmaceuticals. 2020;34(4):505-512. doi:10.1007/s40259-020-00431-0
5. Rezk MF, Pieper B. Outcomes of treatment with biosimilars: being aware of the nocebo effect. Rheumatol Ther. 2017;4(2):209-218. doi:10.1007/s40744-017-0085-z
6. Lu X, Hu R, Peng L, Liu M, Sun Z. Efficacy and safety of adalimumab biosimilars: critical current clinical data in rheumatoid arthritis. Front Immunol. 2021;12:638444. doi:10.3389/fimmu.2021.638444
7. Bhat S, Patel M, Duly K, Choi D. Adalimumab-adbm: the first interchangeable biosimilar for the treatment of inflammatory diseases. Ann Pharmacother. 2022;56(12):1356-1364. doi:10.1177/10600280221082196
8. Barbier L, Ebbers HC, Declerck P, Simoens S, Vulto AG, Huys I. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review. Clin PharmacolTher. 2020;108(4):734-755. doi:10.1002/cpt.1836
9. Cyltezo. Information leaflet. Boehringer Ingelheim Pharmaceuticals Inc; 2023. Accessed May 26, 2023. https://content.boehringer-ingelheim.com/DAM/53ff8c4d-b71e-4879-9145-afac01099275/cyltezo-us-ifu.pdf
10. A closer look at FDA interchangeable biosimilar approvals. National Association of Pharmacy Councils. February 11, 2022. Accessed May 26, 2023. https://nabp.pharmacy/wp-content/uploads/2022/02/Presentation-Handouts-A-Closer-Look-at-FDAs-Interchangeable-Biosimilar-Approvals.pdf
11. Amjevita. Prescribing information. Amgen USA Inc; 2023. Accessed May 26, 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b7178e36-6787-45ab-8fee-be59bc6a4aa4&type=display
12. Umira. Prescribing information. AbbVie Inc; 2021. Accessed May 26, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125057s417lbl.pdf
13. Egilman AC, Van de Wiele VL, Rome BN, et al. Frequency of approval and marketing of “skinny” labeled biosimilars and related Medicare savings. JAMA Trainee Med. 2023;183(1):82-84 . doi:10.1001/jamaininternmed.2022.5419
14. Walsh BS, Bloomfield D, Kesselheim AS. A court decision on thin labeling: Another challenge for cheaper drugs. JAMA. 2021;326(14):13711372. doi:10.1001/jama.2021.0006
15. Orphan drug designations and approvals. FDA. Accessed April 17, 2023. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=446414
16. Yazdany J. Missed Launch: Biosimilars sales continue to decline in the US. Rheumatol arthritis. 2020;72(6):870-873. doi:10.1002/art.41203
17. Insights on the launch of the biosimilar Amjevita and Humira in mid-2023. IPD analysis. February 2023. Accessed March 17, 2023. https://www.ipdanalytics.com/news
18. Insights into the launch of interleukin biosimilars. IPD analysis February 2023. Accessed April 17, 2023. https://www.ipdanalytics.com/news
About the Authors
Stephanie Pilat, PharmD, is a clinical pharmacist at the University of Rochester Specialty Pharmacy in Buffalo, New York.
Viktoriya Avlasevich, PharmD, is an administration and resident PGY-2 specialty pharmacy manager at the University of Rochester Medical Center in New York.
Lisa Cristofaro, PharmD, BS, BCACP, is a market access manager at the University of Rochester Specialty Pharmacy in Pittsford, New York.
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