Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants

• Published in: Clinical pharmacology in drug development Vol. 14; no. 1; pp. 26 - 35
• Main Authors: el Baghdady, Assem, Lledó‐García, Rocío, Gayfieva, Maryam, Lowcock, Romana, Watanabe, Shikiko, Sidhu, Jagdev, Wilkes, Denisa
• Format: Journal Article
• Language: English
• Published: United States 01.01.2025
• Subjects: bioequivalence; ethnicity; FcRn; pharmacokinetic; rozanolixizumab; FcRn; ethnicity; pharmacokinetic; bioequivalence; rozanolixizumab
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.1484

Rozanolixizumab is an anti‐human neonatal Fc receptor humanized immunoglobulin (Ig) G4 monoclonal antibody that reduces IgG, including pathogenic IgG autoantibodies. Rozanolixizumab safety and tolerability have been assessed in previous clinical studies with predominantly White participants. We assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of rozanolixizumab in healthy Japanese and Chinese participants compared with White participants. This double‐blind, single‐center, UK‐based, Phase 1 study randomized 65 participants to rozanolixizumab 4 mg/kg (Japanese and White participants only), 7  mg/kg, or 10 mg/kg. All treatment‐emergent adverse events (TEAEs) were mild to moderate in severity; no severe TEAEs, serious TEAEs, or TEAEs leading to discontinuation occurred. Incidences of TEAEs in Japanese and Chinese participants were comparable to those in White participants. Japanese and Chinese participants had lower systemic rozanolixizumab exposure relative to Caucasian participants, attributable to lower actual doses administered due to lower body weight in Chinese and Japanese participants, indicating that body weight is not a relevant predictor of rozanolixizumab pharmacokinetics. All 3 ethnicities demonstrated dose‐dependent IgG reductions, with IgG nadir achieved around Day 10 and gradual return to baseline levels by Day 56. These data support the applicability of safety data from previous clinical studies of rozanolixizumab to individuals of Japanese and Chinese ethnicity.