UCB Shares Promising Phase 2a Results for Bepranemab in Early Alzheimer's at CTAD 2024

BRUSSELS, Belgium, October 31, 2024 - UCB has announced the Phase 2a results from the TOGETHER (AH0003) study concerning bepranemab, an investigational anti-tau antibody aimed at the mid-region of the tau protein, in patients with prodromal to mild Alzheimer’s disease. The findings were disclosed at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) meeting held in Madrid, Spain, from October 29 to November 1, 2024.

Alistair Henry, Chief Scientific Officer at UCB, expressed optimism about the proof-of-concept data for bepranemab, which suggests its potential in altering the progression of early Alzheimer’s disease. "This reinforces our confidence in targeting the mid-region of tau as a crucial approach in changing the disease’s course," Henry noted. He also extended gratitude to the patients, their families, and the clinical trial teams for their invaluable support in the research.

In the overall study population, bepranemab, administered at both low and high doses, did not exhibit a significant advantage over placebo in the primary endpoint, which was the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score at Week 80. This scale assesses both cognition and function. However, at Week 80, bepranemab showed positive effects on key secondary endpoints at dosages of 45mg/kg and 90mg/kg.

The study further identified consistent treatment benefits in two predefined subgroups: individuals with low tau burden at Baseline and those who are APOε4 non-carriers. In these groups, high-dose bepranemab (90mg/kg) demonstrated advantages across multiple outcome measures. A post-hoc subgroup analysis, involving participants with low baseline tau or those who are APOε4 non-carriers (about half of the total study population), also showed that high-dose bepranemab had favorable outcomes.

Conversely, in the subgroup with high tau levels at Baseline who were also APOε4 carriers, high-dose bepranemab did not present benefits across almost all clinical endpoints. In these participants, the results on CDR-SB, A-iADL-Q, and ADCS-ADL scores favored the placebo.

Regarding safety, bepranemab had an acceptable profile and was generally well tolerated. Brain hemorrhagic and inflammatory changes were comparable between the placebo and bepranemab treatment arms. The incidence of Treatment Emergent Adverse Events (TEAEs), drug-related TEAEs, and TEAEs leading to dropout were similar across the different treatment groups. The most frequently reported TEAEs were infections and infestations (placebo 50.3% / bepranemab 50.2%), nervous system disorders (placebo 40.1% / bepranemab 35.2%), and musculoskeletal disorders (placebo 26.8% / bepranemab 28.3%).

The TOGETHER study is a Phase 2a double-blind, placebo-controlled trial with three arms, randomizing patients to receive either placebo, low-dose, or high-dose bepranemab. A total of 466 patients were enrolled and received treatment in the double-blind phase for 80 weeks. The majority of participants have now transitioned to a 48-week open-label extension (OLE), receiving bepranemab for 44 weeks, followed by a safety follow-up visit 20 weeks after the last infusion.

Bepranemab is a monoclonal antibody (mAb) that specifically targets a mid-region epitope of human tau. In pathological conditions, this mid-region is believed to be crucial for tau aggregation and is a key driver of neurodegeneration in Alzheimer’s disease.