Etanercept Biosimilar Demonstrates Bioequivalence in Phase 3 Study

Valentyna Pekhenko, MD, PhD

Credit: Bogomolets National Medical University

Among a cohort of patients with moderate to severe rheumatoid arthritis (RA), an etanercept biosimilar showed bioequivalence to the reference drug regarding safety, efficacy, and immunogenicity, according to findings from a phase 3 clinical randomized trial published in Medicine.¹

Tumor necrosis factor (TNF) inhibitors, such as etanercept, are commonly used to treat RA as TNF leads to increased pathogenetic gene expression and upregulated production of inflammatory cytokines. In fact, the first biological agent used to treat RA was an anti-TNF-α monoclonal antibody introduced to market more than 2 decades ago. Since then, several TNF inhibitors have been approved and are widely used in clinical practice.²

“Etanercept is effective in improving the symptoms and pain levels in people with RA, but long-term monitoring is needed,” wrote a team of investigators led by Valentyna Pekhenko, MD, PhD, associated with the Department of General Practice at Bogomolets National Medical University, Medical Center, in Kyiv, Ukraine. “According to analytical comparisons and studies, the etanercept biosimilar and its reference biologic shown similar therapeutic outcomes. However, there are still relatively few reports on bio-etanercept for the treatment of RA.”

To evaluate the therapeutic equivalence of the etanercept biosimilar and the original etanercept among patients with RA, investigators randomized patients 1:1 to receive 25 mg of either drug twice weekly for 24 weeks. The primary endpoint was the number of patients who achieved an American College of Rheumatology 20% improvement (ACR20) response at the end of the trial. Immunogenicity and safety, as determined by adverse reactions and adverse events, were also evaluated.

A total of 79 patients were placed in the biosimilars cohort and 77 received the reference drug. At the 4-week follow-up period, 82.3% (n = 65) of patients in the biosimilars group and 90.9% (n = 70) in the reference drug group achieved an ACR20 response. No significant difference across treatment arms were observed (P = .16) and no significant differences in adverse reactions or adverse events were reported, regardless of severity. Antibody development was observed in 5.1% (n = 4) of patients at visit 6, 5.0% (n = 4) at visit 9, and 3.8% (n = 3) at visit 11. Results were similar in the reference drug cohort, with 6.4% (n = 5) developing antibodies at visit 6, 6.5% (n = 5) at visit 9, and 4.1% (n = 3) at visit 11. These differences were not significant (P > .99).

Investigators mentioned limitations of the study including the nonblinded study design, which may have impacted findings. As the reference drug has been on the market for a number of years, its safety and efficacy has been fully validated in premarketing clinical trials using a large body of post-marketing clinical data. The current trial has been designed to meet the objectives of the study, accounting for the clinical needs of patients and the clinical safety of the bio-originator. The generalizability of the findings to other diseases may be limited due to only including patients with RA. The small sample size, the time, and the location of the study may have further hindered representativeness.

“The results of this study add to the current knowledge and understanding of the efficacy, safety, and potential immunogenicity of etanercept in the treatment of RA,” investigators concluded. “The studies demonstrate the high similarity in safety, efficacy and immunogenicity between biosimilar etanercept and [original] etanercept.”

References

1. ^{Pekhenko V, Udovitskiy V, Barbukho O. Efficacy, safety and immunogenicity of the biosimilar etanercept compared to the reference formulation original etanercept in patients with rheumatoid arthritis: An open-label, randomized, comparative, multicenter study. Medicine (Baltimore). 2024;103(30):e39060. doi:10.1097/MD.0000000000039060}
2. ^{Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320:1360–72}