Bio-Thera Releases Phase I Results for BAT4406F in Neuromyelitis Optica Spectrum Disorders

GUANGZHOU, China I January 14, 2025 I Bio-Thera Solutions, Ltd. has released the results of its Phase I clinical study for BAT4406F, a fully humanized monoclonal antibody enhanced with antibody-dependent cell-mediated cytotoxicity (ADCC). This study, published in CNS Neuroscience & Therapeutics, involved Chinese patients suffering from neuromyelitis optica spectrum disorders (NMOSD).

NMOSD is a rare autoimmune condition targeting the central nervous system, leading to severe inflammation and demyelination. Symptoms primarily include acute optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which can result in significant loss of vision, paralysis, and damage to bladder and rectal functions. Treatments involving monoclonal antibodies against CD20, aimed at depleting B-cells, have shown promise in reducing the recurrence of NMOSD and mitigating neurological decline.

The drug, BAT4406F, represents a significant advancement in NMOSD treatment. As a glycosylation-optimized anti-CD20 monoclonal antibody of the IgG1 subclass, it showcases enhanced ADCC effectiveness. Preclinical evaluations revealed that BAT4406F achieves more potent B-cell depletion than other marketed anti-CD20 antibodies like rituximab.

The Phase I study was designed to evaluate BAT4406F's tolerability, safety, pharmacokinetics, pharmacodynamics, and immunogenicity in NMOSD patients. This open-label, dose-escalation study included 15 participants who received a single infusion of BAT4406F. Doses ranged from 20 mg to 750 mg, followed by a six-month observation period. The study's identifier is NCT04146285.

Throughout the study, no dose-limiting toxicities were reported. BAT4406F demonstrated a favorable safety profile with most adverse events being mild to moderate. Importantly, no severe drug reactions were noted. As doses increased, there was a corresponding rise in maximum concentration and area under the curve, while clearance and volume of distribution decreased. The drug's elimination half-life varied between 9.0 and 16.4 days, and its pharmacokinetic profile was generally nonlinear.

BAT4406F's administration resulted in rapid and sustained B-cell depletion across all dose groups. The extent and duration of B-cell suppression were dose-dependent. During the observation period, 86.7% of the subjects did not experience any relapse, and only 13.3% had relapses. By day 180, patients in the higher dose groups (100 mg, 500 mg, and 750 mg) exhibited improved scores on the expanded disability status scale (EDSS) compared to baseline.

There were no significant effects of anti-drug antibody presence on the pharmacokinetics, safety, or efficacy of BAT4406F, as none of the subjects with detectable antibodies were neutralizing antibody-positive.

The study concluded that BAT4406F was well tolerated and successfully achieved significant long-term B-cell depletion in NMOSD patients. This establishes promising preliminary evidence of its efficacy as a maintenance therapy for NMOSD. Building on these findings, Bio-Thera Solutions is advancing to a Phase II/III multicenter, randomized, double-blind, placebo-controlled trial for BAT4406F in Chinese NMOSD patients, identified as NCT06044350.