Tocilizumab Biosimilar MSB11456 Demonstrates Comparable Safety, Efficacy

Anna Zubrzycka-Sienkiewicz, MD, PhD

Credit: ZnanyLekarz.pl

Safety, efficacy, and immunogenicity equivalence was demonstrated between the European Union (EU)-approved tocilizumab reference drug and proposed biosimilar, MSB11456, according to research published in Rheumatic and Musculoskeletal Diseases.¹

To be considered a biosimilar, a drug must exhibit no clinically meaningful differences regarding pharmacokinetics, pharmacodynamics, immunogenicity, purity, structure, safety, and efficacy.²

“The proposed tocilizumab biosimilar MSB11456 has the potential to expand access to interleukin-6 inhibitors for patients with moderate to severe rheumatoid arthritis (RA),” wrote lead investigator Anna Zubrzycka-Sienkiewicz, MD, PhD, associated with the Reumatika Center for Rheumatology in Warsaw, Poland, and colleagues.

The multicenter, randomized, double-blind, multinational, parallel-group study evaluated the safety, efficacy, and immunogenicity of MSB11456 compared with the reference drug. Eligible patients, recruited from 81 European sites, had moderate to severe active RA and an inadequate clinical response to ≥1 disease-modifying antirheumatic drug (DMARD), either synthetic or biologic, treated with methotrexate. Moderate to severe active RA was determined using swollen joint count (≥ 6) and tender joint count (≥ 6), a C-reactive protein ≥ 10mg/L and/or or erythrocyte sedimentation rate ≥ 28 mm/hour at screening, and radiographic evidence within the past 6 months of ≥ 1 joint exhibiting erosion caused by RA at screening.

Patients were randomized to receive 24 weekly injections of either subcutaneous MSB11456 or tocilizumab (162 mg). The study was comprised of a screening period of up to 28 days, a double-blind 24-week treatment period, an extended 28-week double-blind treatment program during which participants in the reference drug cohort were randomized to either continue treatment or switch to the biosimilar group, and a 12-week safety evaluation period.

The primary objective was the equivalent efficacy at 24 weeks between the proposed biosimilar and the reference drug, while the key secondary endpoint was a 20% improvement according to American College of Rheumatology (ACR) criteria (ACR20). Additional endpoints included early efficacy, defined as change from baseline in Disease Activity Score-28 Joint Count with erythrocyte sedimentation rate (DAS28-ESR) at week 12, achievement of ACR50/70, change in DAS28-CRP from baseline, and changes in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) throughout the study period.

Equivalence was determined using the mean change from baseline to week 24 in DAS28-ESR between treatments. Safety and immunogenicity were also analyzed to week 55.

The study enrolled and randomized 604 subjects, with 302 placed in the biosimilar group and 302 placed in the reference product.

Clinical equivalence was demonstrated for the primary and key secondary endpoints. At week 24, the least squares mean differences in the change from baseline in DAS28-ESR among treatment groups was .01 (95% confidence interval [CI] −0.19 — .22). ACR20 response rates were > 80% at week 24 among both cohorts and the early efficacy endpoint results confirmed comparability. Similarity was also observed for immunogenicity, safety, and efficacy, including patients who switched from tocilizumab to the biosimilar at week 28. Most treatment-emergent adverse events were comparable among patients receiving MSB11456 and tocilizumab and categorized as grade 1 or 2 in severity.

As investigators needed to ensure homogeneity between patients to maximize the sensitivity, subjects were all White, from Eastern Europe, a body weight of <100kg, predominantly biologic-naïve, and had long-standing RA. However, this homogeneity may have hindered findings by limiting generalizability.

“This study adds to the increasing body of evidence that the clinical effects of the proposed biosimilar MSB11456 are similar to those of the EU-approved tocilizumab,” investigators concluded.

References

1. ^{Zubrzycka-Sienkiewicz A, Klama K, Ullmann M, et al. Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study. RMD Open. 2024;10(1):e003596. Published 2024 Feb 5. doi:10.1136/rmdopen-2023-003596}
2. ^{US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Scientific considerations in demonstrating biosimilarity to a reference product. guidance for industry. 2015a. Available: https://www.fda.gov/media/82647/download}