Ninth Adalimumab Biosimilar, Yuflyma, Approved in the US

The FDA has approved a ninth adalimumab (Humira) biosimilar. Yuflyma (adalimumab-aaty) from Celltrion Healthcare already has a launch date in July due to an agreement with AbbVie, the maker of the reference product.

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Yuflyma is a high-concentration (100 mg/mL), citrate-free formulation, which means patients will inject a smaller volume and there will be less injection-site pain. Not all approved adalimumab biosimilars are the high-concentration/citrate-free formulations.

“Currently, more than 80% of patients treated with Humira in the United States rely on a high-concentration and citrate-free formulation of this medication,” Jonathan Kay, MD, professor, UMass Chan Medical School, said in a statement. “The availability of a high-concentration and citrate-free formulation adalimumab biosimilar provides an important treatment option for patients with inflammatory diseases who benefit from this effective therapy.”

The approval of Yuflyma is for 8 conditions: rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa.

Yuflyma will join a crowded field of adalimumab biosimilars, led by Amjevita, which has been on the market since January 31, 2023. There are 7 other adalimumab biosimilars expected to launch in July. The approval of multiple adalimumab biosimilars is expected to help bring down the cost of Humira, which is a top-selling drug and has had patent exclusivity for 20 years.

In February, Reuters reported that AbbVie expects sales of Humira to decline 37% in 2023 due to the competition of less expensive adalimumab biosimilars. Over those 20 years of exclusivity in the United States, Humira has brought in $200 billion in revenue for the company.

In addition to the 9 approved biosimilars, there is another awaiting approval: Alvotech’s AVT02, which has received 2 complete response letters due to deficiencies in the company’s manufacturing facility.

Celltrion is also seeking interchangeability designation for Yuflyma, which the company tentatively expects in the fourth quarter of 2024. Currently, there is only 1 interchangeable adalimumab biosimilar approved—Cyltezo from Boehringer Ingelheim. However, an interchangeability application for Abrilada from Pfizer is under review by the FDA, as is an application for AVT02.

Yuflyma’s approval is based on analytical, preclinical, and clinical studies demonstrating the agent is comparable to the reference product.

Kay was the lead investigator on a safety and efficacy study comparing Yuflyma with the reference product. The results were published in 2021 in Arthritis Research & Therapy.¹ The randomized, double-blind phase 3 study reported on results to week 24. Patients with active rheumatoid arthritis were randomly assigned 1:1 to receive either Yuflyma or European Union–approved adalimumab.

The study found the ACR20 response rate (a 20% improvement in disease) at week 24 was 82.7% in both groups, and additional end points and overall safety were comparable between the groups.

In a switching study, Yuflyma had comparable efficacy, pharmacokinetics, safety, and immunogenicity compared with the reference product after 1 year of treatment that included switching from the reference to the biosimilar. The results were published in Rheumatology in 2022.²

References

1. Kay J, Jaworski J, Wojciechowski R, et al. Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study. Arthritis Res Ther. 2021;23(1):51. doi:10.1186/s13075-020-02394-7

2. Furst DE, Jaworski J, Wojciechowski R, et al. Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(4):1385-1395. doi:10.1093/rheumatology/keab460