Efficacy and safety of rademikibart (CBP-201), a next-generation monoclonal antibody targeting IL-4Rα, in adults with moderate-to-severe atopic dermatitis: a phase 2 randomized trial (CBP-201-WW001)

Background Rademikibart (CBP-201) is a next-generation IL-4Rα-targeting antibody. Objective To evaluate rademikibart in adults with moderate-to-severe atopic dermatitis. Methods 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg Q4W; plus 600-mg loading dose) or placebo. Randomization began July 2020. The trial completed October 2021. Results The WW001 phase 2 trial achieved its primary endpoint: significant percent reduction from baseline in least squares (LS) mean Eczema Area Severity Index (EASI) to Week 16 with rademikibart 300 mg Q2W (-63.0%; p=0.0007), 150 mg Q2W (-57.6%; p=0.0067), 300 mg Q4W (-63.5%; p=0.0004) versus placebo (-39.7%). EASI decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (Week 2), with no evidence of plateauing by Week 16. Significant improvements were also observed in secondary endpoints, including pruritus. Across the primary and secondary endpoints, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to COVID-19, pandemic-related restrictions likely impacted trial conduct. Conclusion Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies.