P012 Therapeutic equivalence of an omalizumab biosimilar (ADL-018) to the European Union-approved reference omalizumab in chronic spontaneous urticaria

Abstract

This study evaluated the therapeutic equivalence of ADL-018 to the European Union-approved reference omalizumab (EU-OMA) in patients with chronic spontaneous urticaria unresponsive to H1-antihistamines. This randomized, double-blind, four-arm, parallel-group, active-controlled phase III trial (NCT05774639) included two 12-week treatment periods. In treatment period 1, participants were randomized (2 : 2 : 1 : 1) to ADL-018 or EU-OMA (300 mg or 150 mg) administered subcutaneously at weeks 0, 4 and 8. Treatment period 2 was the single transition period. Here we report results from treatment period 1, comparing ADL-018 (300 mg) to EU-OMA (300 mg). The primary endpoint was the change in Itch Severity Score (ISS7) from baseline to week 12. Secondary endpoints, immunogenicity and safety were also assessed. Overall, 600 patients were randomized: 200 to ADL-018 (300 mg), 100 to ADL-018 (150 mg), 200 to EU-OMA (300 mg) and 100 to EU-OMA (150 mg). Therapeutic equivalence was demonstrated between ADL-018, 300 mg and EU-OMA, 300 mg. The mean change from baseline of ISS7 by week 12 was −9.98 for ADL-018, 300 mg and −9.82 for EU-OMA, 300 mg. The least square mean (LSM) difference was −0.16 (90% confidence interval −0.66 to 0.34), with the confidence interval between predefined equivalence margins of −2.5 and +2.0. Secondary endpoints showed significant improvement and were comparable after 4, 8 and 12 weeks. The greatest Dermatology Life Quality Index improvements were observed by week 12, with a LSM change from baseline of −7.50 for ADL-018, 300 mg and −7.64 for EU-OMA, 300 mg. All treatment arms showed clinically meaningful reductions in Urticaria Activity Score through week 12: − 21.3 for ADL-018, 300 mg and −20.7 for EU-OMA, 300 mg. By week 12, the mean change from baseline ranged from −8.65 to −11.2, with ADL-018, 300 mg showing the greatest reduction in Hives Severity Score. Immunogenicity findings indicated that 27% of patients receiving ADL-018, 300 mg were positive for antidrug antibodies, compared with 21.5% for EU-OMA, 300 mg. No serious adverse events occurred. Treatment-emergent adverse events occurred in 7.7% of patients, with the highest rate (12.9%) noted in the EU-OMA, 300 mg group switched to ADL-018, 300 mg. The safety profiles, including injection-site reactions, were comparable between these two groups. In conclusions, the results demonstrate that AD-018, 300 mg is therapeutically equivalent to EU-OMA, 300 mg.