Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating autoimmune disease affecting the central nervous system. A recent first-in-human dose-escalation Phase I clinical study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BAT4406F, an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced fully humanized anti-CD20 monoclonal antibody, in Chinese NMOSD patients.
Fifteen patients were enrolled and received BAT4406F in doses ranging from 20 to 750 mg. The study utilized a "3 + 3" design for dose escalation and followed patients for a 6-month observation period. Key findings included:
- Safety: BAT4406F was well-tolerated, with no dose-limiting toxicities observed. Adverse events were mostly of CTCAE Grade 1 or 2, and no serious adverse drug reactions occurred.
- Pharmacokinetics: The maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) increased with dose, while clearance and volume of distribution decreased. The elimination half-life ranged from 9.0 to 16.4 days.
- Pharmacodynamics: BAT4406F led to rapid and significant B-cell depletion across all dose groups. Doses of 500 mg or 750 mg maintained CD19+ B lymphocyte counts below 10/μL for the entire observation period.
- Efficacy: Preliminary evidence suggested BAT4406F's potential in NMOSD maintenance treatment, with decreased expanded disability status scale (EDSS) scores in several groups and a low relapse rate (13.3%) during the observation period.
In conclusion, BAT4406F demonstrated favorable safety and pharmacodynamic profiles, with significant and long-term depletion of CD19+ B lymphocytes. The study's findings support further investigation into BAT4406F's efficacy and safety in treating NMOSD.
