FDA approvals of these biosimilars started in 2016, but only 1 such product has successfully launched.
In recent years, the evolving landscape of biosimilars has contributed to an overwhelming amount of information flooding the market. In the dermatology space, approvals of biosimilars for adalimumab, a tumor necrosis factor inhibitor used for the treatment of moderate to severe plaque psoriasis and hidradenitis suppurativa (HS), have been occurring since 2016; however, only recently has the first one been launched. Adalimumab-atto (Amjevita; Amgen) hit the market on January 31, 2023, and has exclusivity until July 2023. Eight to 10 additional adalimumab biosimilars will potentially launch between July and December 2023.1
In March 2010, the Biologics Price Competition and Innovation Act, as part of the Affordable Care Act, included a standardized approval pathway for biologic, biosimilar, and interchangeable products. After a 10-year transition period, biosimilar products must now be approved under a biologics license application.1 This abbreviated approval pathway for biosimilars does not routinely require clinical studies to reestablish efficacy and safety like the comprehensive new drug applications that were previously required. Instead, the manufacturer must demonstrate the proposed product is biosimilar to an FDA-approved reference product using comparative testing of safety, purity, and potency.2-5 Approved adalimumab biosimilars have consistently demonstrated these qualifications in clinical trials.6
Biosimilars cannot automatically be substituted for a reference product at the pharmacist level without prescriber permission unless the biosimilar has been granted interchangeable status (subject to state laws).7 Switching studies must be conducted for interchangeable products to demonstrate that switching between the proposed product and reference product does not increase safety risks or decrease efficacy compared with using the reference product without switching. If a product is initially approved as a biosimilar, it can later be approved as interchange-able upon submission of a supplemental application addressing interchangeability standards.8 There is currently 1 inter-changeable biosimilar of adalimumab, adalimumab-adbm (Cyltezo; Boehringer Ingelheim), which was approved in August 2017 and granted interchangeability desig-nation in October 2021. Adalimumab-adbm is expected to launch in July 2023, with interchangeability market exclusivity held for approximately 1 year.9
Following FDA approval, any differences in the biosimilar product’s concentration, preservative content, package size, and the commercially available device in comparison to the reference product’s are permissible; this is of particular interest for adalimumab biosimilars. Adalimumab (Humira; AbbVie) is currently available in a high-concentration (40 mg/0.4 mL), citrate-free formulation, as well as in the original concentration (40 mg/0.8 mL), which contains citrate; both are commercially available in a prefilled syringe or autoinjector. Currently, most adalimumab use consists of the high-concentration formulation. Biosimilars anticipated to launch in July 2023 include both high and original concentration formulations. Biosimilar adalimumab-atto is available as a citrate-free prefilled syringe or autoinjector, with a concentration of 40 mg/0.8 mL, which is the original concentration.10,11 Adalimumab is commonly first prescribed and 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 may present potential points of confusion for the provider, pharmacy, and patient.
A reference product may have unexpired exclusivity for a particular indication that 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 skinny label. In this way, biosimilars do not automatically adopt all previously patent-protected indications upon expiration of the reference product’s patents. Each biosimilar sponsor can file supplemental applications to seek approval for additional indications upon reference product patent expiration.13,14
For example, the orphan drug exclusivity (ODE) patent for adalimumab for HS expired on September 9, 2022. Adalimumab-atto and adalimumab-adbm were not initially approved with the HS indication, but this was added as an indication for both products in March 2023. The indication of adolescent HS is protected by ODE until October 16, 2025, after which point each biosimilar sponsor can seek approval.9,11,15
The launching of biosimilars increases competition for the reference product and introduces opportunity for price reductions. The anticipated market share of adalimumab biosimilars remains unknown, as pharmacy benefit manager and payer negotiations 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 the expected biosimilar launches beginning in July 2023, payers may begin to prefer certain products through a tiered formulary.
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 on most formularies in 2023 and on a high percentage of formularies in 2024.17
AbbVie reached licensing and settlement agreements with several biosimilar sponsors; however, it may be pressured to provide significant rebates to maintain its market share. Ustekinumab (Stelara; Janssen Biotech, Inc) will be the next biologic commonly prescribed in the dermatology space to lose 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 into clinical practice will remain somewhat dependent on prescriber inertia, tiered formulary adjustments, and patient preferences. However, this may gradually begin to cloud the status quo as further options become available on the market.
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 towards a tailored clinical biosimilar development. BioDrugs. 2020;34(3):297-306. doi:10.1007/s40259-020-00422-1
3. White J, Goldman J. Biosimilar and follow-on insulin: the ins, outs, and interchangeability. J Pharm Technol. 2019;35(1):25-35. doi:10.1177/8755122518802268
4. Zhang RM, Puri R, McGill JB. Update on biosimilar insulins: a US perspective. BioDrugs. 2020;34(4):505-512. doi:10.1007/s40259-020-00431-0
5. Rezk MF, Pieper B. Treatment outcomes with biosimilars: be 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: current critical 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 Pharmacol Ther. 2020;108(4):734-755. doi:10.1002/cpt.1836
9. Cyltezo. Package insert. 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’s interchangeable biosimilar approvals. National Association of Boards of Pharmacy. 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. Humira. 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 biosimilars with a skinny label and associated Medicare savings. JAMA Intern Med. 2023;183(1):82-84. doi:10.1001/jamainternmed.2022.5419
14. Walsh BS, Bloomfield D, Kesselheim AS. A court decision on “skinny labeling”: another challenge for less expensive 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. Failure to launch: biosimilar sales continue to fall flat in the United States. Arthritis Rheumatol. 2020;72(6):870-873. doi:10.1002/art.41203
17. Amjevita and mid-2023 Humira biosimilar launch insights. IPD Analytics. February 2023. Accessed March 17, 2023. https://www.ipdanalytics.com/news
18. Interleukin biosimilar launch insights. IPD Analytics 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 a PGY-2 specialty pharmacy administration and leadership resident at University of Rochester Medical Center in New York.
Lisa Cristofaro, PharmD, BS, BCACP, is a manager of market access at University of Rochester Specialty Pharmacy in Pittsford,New York.