A Randomized Pharmacokinetic Study in Healthy Male Subjects Comparing a High-concentration, Citrate-free SB5 Formulation (40 mg/0.4 ml) and Prior SB5 (Adalimumab Biosimilar)

• Published in: Rheumatology and therapy. Vol. 9; no. 4; pp. 1157 - 1169
• Main Authors: Ahn, So-shin, Lee, Minkyung, Baek, Yumin, Lee, Sukho
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.08.2022; Springer Nature B.V
• Subjects: Bioequivalence; Biological products; Family Medicine; General Practice; Internal Medicine; Medicine; Medicine & Public Health; Monoclonal antibodies; NCT; NCT04514796; Original Research; Orthopedics; Quality of Life Research; Rheumatology; Tumor necrosis factor-TNF; Bioequivalence; Pharmacokinetics; TNF inhibitor; Biosimilar; SB5
• ISSN: 2198-6576; 2198-6584
• DOI: 10.1007/s40744-022-00471-8

Introduction SB5 is an approved biosimilar of adalimumab, a monoclonal anti-tumor necrosis factor (anti-TNF) antibody. This study compared pharmacokinetics (PK), safety, tolerability, and immunogenicity between a new high-concentration, low-volume, and citrate-free formulation (40 mg/0.4 ml, SB5-HC) and the current low-concentration formulation with higher volume (40 mg/0.8 ml, SB5-LC) to evaluate the bioequivalence of the two formulations. Methods This study was a randomized, single-blind, two-arm, parallel-group, single-dose study in healthy male subjects. Subjects were randomized to receive either SB5-HC or SB5-LC via subcutaneous injection using a pre-filled syringe. Primary endpoints were the area under the curve of the concentration–time curve from zero to infinity (AUC inf ) and maximum serum concentration (C max ). Bioequivalence was achieved if the 90% confidence intervals (CIs) for the ratios of the geometric least squares mean (LSMean) of primary endpoints were within the pre-defined bioequivalence margins of 0.80–1.25. Secondary endpoints included safety, tolerability, and immunogenicity. Results Subjects ( n  = 188) were randomized to SB5-HC ( n  = 94) or SB5-LC ( n  = 94). Baseline characteristics were comparable between the two treatment groups. The mean values for AUC inf and C max were similar between the SB5-HC and SB5-LC groups. For the primary endpoints, the geometric LSMean ratios (90% CI) for AUC inf and C max were 0.920 (0.8262–1.0239) and 0.984 (0.9126–1.0604), respectively, placing the corresponding 90% CIs well within the pre-defined bioequivalence margin of 0.80–1.25. All treatment-emergent adverse events (TEAEs) were considered mild to moderate and were reported for 44.7% and 51.1% of subjects in the SB5-HC and SB5-LC groups, respectively. Immunogenicity assessed by frequency of occurrence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) was comparable between groups. Conclusions This bridging study demonstrated PK equivalence and comparable safety and tolerability of subcutaneous injection of SB5 via SB5-HC or SB5-LC. Clinicaltrials.gov identifier https://clinicaltrials.gov/ct2/show/NCT04514796 .