Bioequivalence of a Novel Omalizumab Solution for Injection Compared with the Standard Lyophilized Powder Formulation

Abstract

Aim: To determine the pharmacokinetic (PK) and pharmacodynamic (PD) comparability of a novel solution for injection (solution) and the reference lyophilized powder formulation (powder) of omalizumab. Methods: In this open-label, parallel-group study, adult atopic subjects (serum immunoglobulin [Ig] E 30−300 IU/ ml; body weight, 40−90 kg) received a single subcutaneous dose (150 or 300 mg) of solution or powder omalizumab. Serum concentrations of total omalizumab, free and total IgE and safety were determined up to 84 days post dose. Bioequivalence was examined for dose-normalized parameters of omalizumab in serum: maximum concentration (C max ), area under the concentration-time curve up to the last quantifiable concentration (AUC 0-tlast ) and up to infinity (AUC 0-inf ). Bioequivalence was concluded if the 90% confidence interval (CI) of the ratio of solution vs. powder geometric means was entirely contained within 0.8–1.25. Results: 155 subjects were randomized and dosed (62.6% female; mean age, 34.7 years). Systemic exposure to omalizumab was similar for the two formulations at both doses. PK bioequivalence was demonstrated (n = 153): C max , ratio of geometric means: 1.01 (90% CI: 0.95–1.08); AUC 0-tlast , 0.98 (0.92–1.05); AUC 0-inf , 0.98 (0.91–1.05). Omalizumab mean elimination half-life: 22.1 days for solution; 22.9 days for powder. PD parameters (n = 154) of free and total IgE in serum were comparable between formulations; each produced a 95% reduction from screening in free IgE. Most common adverse events (AEs): headache (23.9%), sinus congestion (8.4%). No serious AEs were reported. Conculsions: The novel, ready-to-use omalizumab solution formulation is bioequivalent to the reference lyophilized powder formulation.