Bio-Thera Solutions has announced the publication of Phase I clinical study results for BAT4406F, an ADCC-enhanced fully humanized anti-CD20 monoclonal antibody, in Chinese patients with neuromyelitis optica spectrum disorders (NMOSD). The study, published in CNS Neuroscience & Therapeutics, assessed the tolerability, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of BAT4406F in NMOSD patients.
NMOSD is a rare immune-mediated central nervous system inflammatory demyelinating disease characterized by severe optic neuritis and longitudinally extensive transverse myelitis. B-cell depletion therapy using anti-CD20 monoclonal antibodies has shown significant therapeutic effects in reducing NMOSD recurrence and slowing neurological dysfunction progression.
BAT4406F: An Enhanced Anti-CD20 Antibody
BAT4406F, a Class 1 innovative drug developed by Bio-Thera, is a glycosylation-optimized fully human anti-CD20 mAb of the IgG1 subclass with an enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect. Preclinical studies indicated that BAT4406F exhibits stronger B-cell depletion activity compared to marketed anti-CD20 monoclonal antibodies, including rituximab.
The Phase I study (NCT04146285) was a first-in-human, open-label, dose-escalation trial involving fifteen eligible Chinese NMOSD patients. Participants were administered a single intravenous infusion of BAT4406F across five fixed-dose groups (20 mg to 750 mg) followed by a 6-month observation period.
Safety and Efficacy Results
The study reported that no subjects experienced dose-limiting toxicities (DLT) at the studied doses. BAT4406F injection demonstrated a favorable safety profile, with most adverse events being CTCAE Grade 1 or 2 in severity. No Grade ≥3 adverse drug reactions (ADR) or serious adverse reactions occurred.
Pharmacokinetic (PK) analysis showed that Cmax, AUC0-t, and AUC0-inf increased with increasing BAT4406F doses, while CL, lZ, and Vd decreased. The mean elimination half-life (T1/2) ranged from 9.0 to 16.4 days. The PK profile of BAT4406F was generally nonlinear. BAT4406F induced rapid and significant B-cell depletion across all dose groups, maintaining B lymphocyte levels at a low level. The duration of B lymphocyte suppression and depletion was dose-dependent. During the observation period, 13 (86.7%) subjects remained relapse-free, and 2 (13.3%) subjects relapsed. On day 180 post-dose, the 100 mg, 500 mg, and 750 mg groups showed decreased expanded disability status scale (EDSS) scores compared to baseline.
Three subjects tested positive for anti-drug antibodies (ADA), but all were neutralizing antibody (NAb)-negative. No significant effects of ADA positivity on PK, safety, pharmacodynamics, or efficacy were observed.
Ongoing Phase II/III Trial
The Phase I study concluded that BAT4406F was well-tolerated and exhibited the expected pharmacodynamic effect of significant and long-term depletion of CD19+ B lymphocytes. BAT4406F also demonstrated preliminary evidence of activity as a NMOSD maintenance treatment. Based on these findings, a Phase II/III multicenter, randomized, double-blind, placebo-controlled trial of BAT4406F in Chinese NMOSD patients is currently underway (NCT06044350).
