Investigational BAT4406F Performs in Phase 2/3 Study of NMOSD, Leading to Early Enrollment Termination

Xiangjun Chen, MD

(Credit: Fudan University)

In a recent company announcement, Bio-Thera Solutions has decided to close patient enrollment for its pivotal phase 2/3 trial (NCT06044350) of BAT4406F, a fully humanized anti-CD20 monoclonal antibody injection for patients with neuromyelitis optica spectrum disorder (NMOSD), following a positive recommendation from an Independent Data Monitoring Committee (IDMC).¹ The company noted that it will begin preparation to file for regulatory approval from China's National Medical Products Administration for BAT4406F.

Led by Xiangjun Chen, MD, a professor of neurology at Fudan University, the randomized, double-blind, placebo-controlled phase 2/3 trial testing BAT4406F is being conducted across 45 sites in China. After a formal review of interim data, the IDMC concluded that BAT4406F displayed statistically significant efficacy, achieving prespecified superiority end points and maintaining a favorable safety profile.

Based on the agent’s compelling efficacy and ability to meet the predefined superiority criteria, the IDMC recommended early trial termination. Eligible patients for the trial were aged 18 to 65 years and met the 2015 International Panel for NMO Diagnosis criteria for NMOSD, with confirmed AQP4-IgG positivity. Patients either had at least 2 years of documented clinical relapse history or experienced at least 1 clinically confirmed relapse in the year prior to screening. Additionally, all participants had an Expanded Disability Status Scale (EDSS) score of 7 or lower. Despite Bio-Thera closing enrollment ahead of schedule for BAT4406F, the company noted it will still assess the safety and efficacy of the investigational therapy in other indications.

BAT4406F is an investigational glycosylation-optimized fully anti-CD20 human mAb of IgG1 subclass with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect. In preclinical research, BAT4406F demonstrated stronger B-cell depletion activity compared with the marketed anti-CD20 monoclonal antibodies, including rituximab. Earlier in the year, January 2025, the company announced the publication of the findings from its phase 1 clinical study (NCT04146285) of BAT4406F in Chinese patients with NMOSD in CNS Neuroscience & Therapeutics.²

READ MORE: Soluble CD83 Levels Reduced in NMOSD and Relapsing MOGAD, Pointing to Potential Biomarker

The phase 1 study was a first-in-human, open-label, dose-escalation trial to evaluate the tolerability, safety, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary efficacy of BAT4406F injection in among Chinese patients with NMOSD. The study set included 15 patients testing 5 fixed dose groups of BAT4406F, ranging from 20-mg to 750-mg, over a 6-month observation period.

At the studied doses, no participants reported experiencing dose limiting toxicities. Overall, BAT4406F injection displayed a favorable safety profile, with most of the adverse events reported as Grade 1 or 2 in terms of severity, and no Grade at least 3 adverse drug reactions or serious adverse reactions occurred in any patients. With the dose increase of BAT4406F, findings showed that C_max, AUC_0-t and AUC_0-inf had an increasing trend, whereas the CL, l_Z, and V_d had decreasing trend. Notably, the mean elimination half-life (T_1/2) ranged from 9.0-16.4 days and PK profile of BAT4406F was generally nonlinear. Researchers reported that BAT4406F led to a rapid and significant B-cell depletion in all dose groups. Furthermore, the company noted that the single dose of BAT4406F administration-maintained B lymphocyte at a low level, and the duration of B lymphocyte suppression and depletion depended on the dose.

During the observation period, 86.7% of participants (n = 13) remained relapse free, and 13.3% of patients (n = 2) relapsed. On day 180 post dose, researchers reported that 100 mg, 500 mg, and 750 mg participant groups had reduced EDSS scores compared with baseline. Additionally, investigators observed that 3 participants were antidrug antibody (ADA) positive and all were neutralizing antibody (NAb)-negative. No apparent effects of ADA positivity on pharmacokinetics, safety, pharmacodynamics, or efficacy were reported in the trial.

REFERENCES
1. IDMC Provides Positive Recommendation for Bio-Thera Solution’s BAT4406F (ADCC-Enhanced Anti-CD20 mAb) in Neuromyelitis Optica Spectrum Disorder Based on Interim Analysis of Pivotal Phase II/III Trial. News Release. Bio-Thera Solutions. Published July 2, 2025. Accessed September 3, 2025. https://www.bio-thera.com/plus/view.php?aid=1196
2. Bio-Thera Solutions Publishes Phase I Clinical Study Results for BAT4406F, an ADCC-Enhanced Fully Humanized Anti-CD20 Monoclonal Antibody, in Patients with Neuromyelitis Optica Spectrum Disorders. News Release. Bio-Thera Solutions. Published January 14, 2025. Accessed September 3, 2025. https://www.bio-thera.com/plus/view.php?aid=1112