Novo Nordisk to enter phase III development in Alzheimer’s disease with oral semaglutide.

Novo Nordisk announced the decision to enter phase III development in Alzheimer’s disease with 14 mg oral semaglutide, a once-daily oral formulation of the long-acting GLP-1 analogue semaglutide. The decision follows evaluation of GLP-1 data from preclinical models, real-world evidence studies, post-hoc analysis of data from large cardiovascular outcomes trials, as well as discussions with regulatory authorities. Novo Nordisk intends to initiate a pivotal phase IIIa programme with approximately 3,700 people with early Alzheimer’s disease. The programme is planned for initiation in the first half of 2021 and will investigate the efficacy and safety of once-daily oral semaglutide, compared to placebo. The expected main treatment period in the trials is around two years. About data from preclinical models, real-world evidence studies and the post-hoc analysis : Animal studies highlight the key effects of GLP-1 relevant for Alzheimer’s disease including improved memory function and reduced phospho-tau accumulation. Semaglutide has specifically been shown to reduce measures of neuro-inflammation which may affect cognition and function. Further, real-world evidence from two Danish nationwide registries, the US Truven claims database and the FDA FAERS database support a potential association between lower risk of dementia following treatment with GLP-1. Finally, in a post-hoc analysis of data from three large cardiovascular outcomes trials conducted by Novo Nordisk (LEADER, SUSTAIN 6 and PIONEER 6), which included 15,820 patients with type 2 diabetes with median follow-up of 3.6 years, a total number of 47 people were identified with development of dementia, of which 32 were on placebo and 15 on GLP-1 (liraglutide or semaglutide). The rate of developing dementia was statistically significantly reduced by 53% in favour of GLP-1.