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)

Abstract

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 highconcentration, 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, singleblind, 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.

Review of Adalimumab Biosimilar SB5 in Immune-Mediated Inflammatory Diseases

“… A randomized, single-blind, two-arm, parallel-group, single-dose, PK, clinical equivalence study in healthy male subjects comparing the SB5-LC and SB5-HC formulations. A total of 188 healthy subjects were randomized (94 subjects in each group) [ 20 ]. …”

“…Furthermore, the SB5-HC citrate-free formulation (40 mg/0.4 mL) showed equivalent PK compared to the initially used SB5-LC citrate-containing formulation (40 mg/0.8 mL) in the dedicated PK clinical equivalence study. The LSMean ratios for AUC inf and C max were 0.920 and 0.984, respectively, with the corresponding 90% CIs well within the predefined bioequivalence margins of 0.80–1.25 [ 20 ].…”

“…The clinical equivalence study dedicated to the comparison of the SB5-LC and SB5-HC formulations revealed comparable safety profiles for the two different formulations. All TEAEs were mild or moderate in intensity and no patient withdrew from the study because of a TEAE [ 20 ]. Overall, the combined safety data from all the studies in the SB5 clinical development program were comparable for SB5 and ADL and for the two different SB5 formulations.…”

“…In the single-dose clinical equivalence study in healthy subjects using the SB5-LC formulation, the overall incidence of ADAs to adalimumab after dosing was 98.4%, 95.2%, and 100.0% in subjects treated with SB5, EU-ADL, and US-ADL, respectively [ 15 ]. In the clinical equivalence study comparing single doses of the two different formulations of SB5 in healthy male subjects, the overall incidence of post-dose ADAs was similar for both formulations, with 93.6% of subjects in the SB5-HC group and 94.7% of subjects in the SB5-LC group having detectable ADAs post dose [ 20 ].…”

“…The observational studies described in this review were conducted with SB5-LC which contains citrate. In a clinical equivalence study that compared the SB5-LC and SB5-HC formulations, the incidence of injection site reactions in the SB5-HC group was lower than that in the SB5-LC group (4 subjects [4.3%] vs. 10 subjects [10.6%]) [ 20 ].…”