On 31 October, the global biopharmaceutical company UCB presented data from its Phase IIa TOGETHER study, evaluating bepranemab in people with prodromal to mild Alzheimer’s disease (AD). The findings were shared during a late-breaking symposium at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Madrid, Spain.
The TOGETHER study enrolled 466 participants, who were treated with either a low or high dose of bepranemab, or placebo, over a period of 80 weeks. The study aimed to assess the safety, efficacy and tolerability of bepranemab, an investigational anti-tau antibody targeting the mid-region of the tau protein. The majority of participants have now entered the 48-week open-label extension (OLE) period, where they receive bepranemab for 44 weeks, followed by a safety follow-up visit scheduled 20 weeks after the final infusion. Findings demonstrated that the trial did not meet its primary endpoint, showing no beneficial effect of bepranemab compared to placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score at Week 80.
However in key secondary endpoints, bepranemab slowed cognitive decline (ADAS-Cog14) and rate of tau accumulation versus placebo. In a deeper analysis of predefined subgroups, low tau burden at baseline and APOε4 non-carriers, consistent high-dose treatment benefit was shown across multiple primary and secondary outcome measures, including cognition and function. In contrast, in the subgroup comprising participants with high tau at baseline who were also APOε4 carriers, no significant benefit from high-dose bepranemab across almost all clinical endpoints was observed. Bepranemab was generally well tolerated. Both the placebo and bepranemab treatment arms reported similar incidences of brain hemorrhagic events and inflammatory changes.
