Pharmacokinetic and Pharmacodynamic Bio‐Similarity of ADL‐018 to Innovator Omalizumab: A Randomized Study in Healthy Adults

Vollständiger Abstract

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Abstract Bioequivalence and safety of ADL‐018, an omalizumab biosimilar, were compared with United States‐licensed omalizumab (US‐OMA) and European Union‐approved omalizumab (EU‐OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL‐018, US‐OMA, or EU‐OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC (0–last) , AUC (0–∞) , and C max , were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80–1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL‐018 vs US‐OMA: AUC (0–last) —1.08, AUC (0–∞) —1.07, C max —1.05; GMRs of ADL‐018 vs EU‐OMA: AUC (0–last) —1.06, AUC (0–∞) —1.06, C max – 1.05; and GMRs of US‐OMA vs EU‐OMA: AUC (0–last) —0.99, AUC (0–∞) —0.99, C max —1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment‐emergent adverse events: ADL‐018, n = 6; US‐OMA, n = 5; EU‐OMA, n = 4) was observed. ADL‐018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.