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The etanercept biosimilar, YLB113 (Nepexto), maintained a favorable efficacy, safety, and immunogenicity profile through week 96.
Results of a post-hoc analysis of a phase 3 study revealed patients with rheumatoid arthritis (RA) receiving the etanercept biosimilar, YLB113 (Nepexto) experienced significantly lower injection-site reactions (ISRs) and injection-site erythema (ISE) when compared with the reference product, etanercept. YLB113, a recombinant fusion protein tumor necrosis factor inhibitor (TNFi), showed long-term safety and sustained efficacy through 96 weeks, according to findings published in International Journal of Rheumatic Diseases.1
“Management [of RA] requires long-term treatment with a significant cost burden,” investigators noted. “Although the conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs delay or halt the progression of joint destruction and deformity, they come with an increased financial burden.”
The open-label extension (OLE) single-arm study (YLB113-003) evaluated immunogenicity, safety, and efficacy, as well as post-hoc incidence of ISRs and ISE, the most common side effect of etanercept, in Japanese patients with RA who completed the final visit from the phase 3, double-blind, randomized, 96-week equivalence study. Patients in the OLE received YLB113 50 mg subcutaneously every 2 weeks, whereas in the original study they were treated with either YLB113 50 mg or etanercept. Both trials required a concomitant maintenance dose of methotrexate.
Endpoints were evaluated through ISRs, ISE, adverse events (AEs), physical examination, and anti-drug antibody (ADA) incidence. Disease Activity Sore 28-joint count (DAS28) assessments were conducted at week 0 (baseline), 12, 24, 48, 72, and 96, and any changes from baseline were evaluated.
Of the 201 patients initially included, 184 patients completed the study. Treatment-emergent AEs (TEAEs) were reported in 93.5% (n = 188/201) of patients, with 10.4% experiencing severe AEs. However, the discontinuation rate due to AEs was only 2.0% (6 events) and most AEs were rated as very mild or moderate. Severe adverse drug reactions were observed in 7 (3.5%) patients.
During the open-label extension portion of the study, 20.0% of patients reported ISRs, with nearly all of which rated as mild. Two participants developed ADAs, which were transient and non-neutralizing. Results were similar to those observed in the phase 3 trial. DAS28 change was 2.22 ± 0.95 at the transition baseline, 2.10 ± 0.91 at week 72, and 2.06 ± 0.89 at week 96. Scores remained low through the end of the study period.
Post-hoc analysis results showed that YLB113 demonstrated a significantly lower incidence of ISRs (n = 10 [3.8%], P < 0.0001) and ISE (n = 5 [1.9%], P < 0.0001) when compared with etanercept (n = 35 [13.8%], P < 0.0001 and n = 25 [9.8%], P < 0.001, respectively).
The long duration of the study enabled investigators to analyze safety and efficacy data over 3 years. However, generalizability may be limited as the trial was conducted in Japan and only included Japanese patients.
“This evidence demonstrates that YLB113 maintained a favorable safety, efficacy, and immunogenicity profile throughout 3 years,” investigators concluded. “The availability of Nepexto can positively impact the lives of patients by offering a safe and effective biosimilar.”
Yamanaka H, Tanaka Y, Hibino T, et al. Lower injection-site reactions and long-term safety, immunogenicity, and efficacy of etanercept biosimilar YLB113: Results from a post-hoc analysis of a double-blind, randomized, phase III comparative study and its open-label extension in patients with rheumatoid arthritis. Int J Rheum Dis. 2023;26(1):108-115. doi:10.1111/1756-185X.14462