Bio-Thera to file for BAT4406F’s approval for NMOSD in China
Company stops trial enrollment after therapy shows 'significant efficacy'
Bio-Thera Solutions has closed patient enrollment ahead of schedule for a pivotal Phase 2/3 clinical trial in China of its investigational therapy BAT4406F due to the treatment’s “compelling efficacy” for neuromyelitis optica spectrum disorder (NMOSD).
The decision is based on a recommendation from an Independent Data Monitoring Committee (IDMC), which suggested the trial could be stopped early because interim results have shown “statistically significant efficacy,” according to a company press release.
The company is now preparing to file for the medication’s regulatory approval in China.
NMOSD is an autoimmune disease in which the immune system mistakenly attacks and destroys healthy parts of the nervous system. The spinal cord and optic nerves, which transmit signals between the eyes and brain, are mainly affected, leading to symptoms like vision loss, pain, and weakness or paralysis.
Central to these inflammatory attacks are self-reactive antibodies produced by immune B-cells. The most common type of NMOSD-causing antibodies are those that target the nervous system protein aquaporin-4 (AQP4).
BAT4406F designed to attach to CD20 protein on B-cell surfaces
BAT4406F is an antibody that’s designed to attach to the CD20 protein on B-cell surfaces, marking them for destruction by the immune system. This should lower B-cell levels, thereby reducing the production of the self-reactive antibodies that drive disease symptoms.
Rituximab, a therapy that’s commonly used off-label for NMOSD, works in a similar way.
However, according to Bio-Thera, BAT4406F has been found to destroy more B-cells than rituximab or other B-cell-targeted therapies in preclinical studies while remaining well tolerated.
In a previous Phase 1 clinical trial (NCT04146285), BAT4406F, given via a single infusion into the bloodstream, was well tolerated at various doses and led to rapid reductions in circulating B-cells among 15 people with NMOSD who were positive for AQP4 antibodies.
Preliminary signs of efficacy were also observed, including reductions in disability and improvements in signs of disease on MRI scans.
The Phase 2/3 clinical study (NCT06044350) set out to enroll around 162 adults with AQP4-NMOSD across dozens of sites in China. Participants were randomly assigned to receive two infusions of BAT4406F (500 mg) or a placebo, given about six months apart, and were monitored for a year.
Certain participants who did not experience any disease recurrence during the main trial, or who had a disease relapse that could be controlled with rescue therapy, were eligible to enter into an open-label extension period and continue receiving BAT4406F.
The study evaluated changes in circulating B-cell and antibody levels with BAT4406F, as well as other pharmacological properties of the medication. Safety-related measures were secondary goals.
Many clinical trials, including this one, involve periodic reviews from an IDMC, which is composed of experts not affiliated with the trial investigators or drug developer, to ensure the safety of trial participants and the integrity of the study.
Committee found BAT4406F met efficacy criteria
The committee usually looks at interim data to recommend whether or not the trial should continue or if any modifications need to be made for a significant effect to be observed.
Bio-Thera now reports that after a formal interim data review, the IDMC found BAT4406F showed statistically significant efficacy, meeting the pre-defined criteria to be considered superior to the placebo.
Essentially, since the study has already met its goals of demonstrating BAT4406F’s efficacy, that means there is no need to continue enrolling participants.
As such, Bio-Thera will instead focus on advancing the treatment toward regulatory approval for NMOSD in China. The company also plans to start exploring BAT4406F’s potential for other indications.
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