Biosimilar Shows Comparable Safety, Efficacy to Reference Product in Patients With RA

Treatment with biosimilar YLB113 (Nepexto) was found to significantly lower injection site reactions (ISRs) and injection site erythema (ISE) versus the reference etanercept in patients with rheumatoid arthritis (RA), according to a post-hoc analysis of a phase 3 study published in the International Journal of Rheumatic Diseases. The recombinant fusion protein tumor necrosis factor inhibitor (TNFi) demonstrated long-term safety and sustained efficacy through the phase 3, double-blind, randomized, 96-week equivalence study, according to the investigators.

“Management [of RA] requires long-term treatment with a significant cost burden,” the study authors wrote. “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) analyzed the immunogenicity, safety, efficacy, and post-hoc incidence of ISRs and ISE. Patients were administered YLB113 50 mg subcutaneously every 2 weeks for the post-hoc analysis. In the original study, patients were administered either YLB113 50 mg or etanercept, with both trials including a concomitant maintenance dose of methotrexate.

Endpoints were evaluated through ISRs, ISE, adverse events (AEs), physical examination, and anti-drug antibody (ADA) incidence. The study also analyzed 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. Among 201 patients initially enrolled in the study, 184 patients completed the trial.

Treatment-emergent AEs (TEAEs) were observed in 93.5% (n = 188/201) of patients, with 10.4% experiencing severe AEs. Despite this, the discontinuation rate because of AEs was just 2.0% (6 events) and most AEs were rated as very mild or moderate. Severe adverse drug reactions were reported in 7 (3.5%) patients.

In the OLE portion of the trial, 20.0% of patients experienced ISRs, nearly all of which were deemed mild. Two participants reported ADAs that were transient and non-neutralizing, which were similar to what was reported 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 were low through the end of the study period. Post-hoc analysis results showed that YLB113 had a significantly lower incidence of ISRs (n = 10 [3.8%], P < 0.0001) and ISE (n = 5 [1.9%], P < 0.0001) vs etanercept (n = 35 [13.8%], P < 0.0001 and n = 25 [9.8%], P < 0.001, respectively).

The study authors said that the long duration of the trial enabled them to evaluate safety and efficacy data over 3 years, but generalizability may be limited because 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,” the study authors wrote. “The availability of Nepexto can positively impact the lives of patients by offering a safe and effective biosimilar.”

Reference

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