New data from the Phase 2a TOGETHER study indicates that bepranemab, an investigational anti-tau antibody, may slow tau accumulation in patients with prodromal to mild Alzheimer's disease. The study, a double-blind, placebo-controlled trial, assessed the efficacy, safety, and tolerability of bepranemab over 80 weeks. While the primary endpoint, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score, did not show a statistically significant difference compared to placebo, the trial revealed notable improvements in a key secondary endpoint. These findings were presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain.
The TOGETHER study (NCT04867616) involved 466 participants with prodromal to mild Alzheimer's disease. Patients were randomized to one of three arms and treated for 80 weeks, with many transitioning to a 48-week open-label extension phase. Bepranemab targets the mid-region of the tau protein, a key component in the neurodegenerative processes of Alzheimer's disease.
Cognitive and Clinical Outcomes
Despite not meeting its primary endpoint, bepranemab demonstrated a statistically significant improvement in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score at week 80. This suggests a potential cognitive benefit associated with the treatment. According to Matthew Barton, PhD, clinical program lead for the bepranemab Alzheimer's program at UCB, “This is the first clinical trial reporting evidence of slowing tau accumulation with an anti-tau antibody, particularly one targeted to the tau mid-region, showing promising cognitive outcomes.”
Implications and Future Directions
These findings warrant further investigation in larger, more diverse patient populations to confirm the efficacy and safety of bepranemab. Future research may also focus on identifying patient subgroups that exhibit greater sensitivity to the treatment. The study's results offer a promising avenue for addressing tau pathology in Alzheimer's disease, an area of significant unmet medical need.
