Novo Nordisk Launches Phase 3 Clinical Trial of Oral Semaglutide for Early Alzheimer's Disease in China, Aiming to Enroll Nearly 2,000 Patients Globally

Source: Medicinal Landscape

China Drug Clinical Trial Registration and Information Disclosure Platform recently announced that Novo Nordisk has launched a randomized, double-blind, placebo-controlled Phase 3 clinical trial (EVOKE plus) in China to study the efficacy and safety of oral semaglutide in subjects with early Alzheimer's disease.

Screenshot source: Chinadrugtrials

Semaglutide is a glucagon-like peptide-1 (GLP-1) analog that shares 94% homology with the amino acid sequence of natural GLP-1 and acts as a GLP-1 receptor agonist. It is reported that this product involved some innovative optimizations to the human GLP-1 peptide chain during development, mainly including enhanced binding to albumin, which reduces renal clearance and protects it from metabolic degradation—this is also the main mechanism behind the extended half-life of semaglutide. Additionally, through peptide chain optimization, semaglutide can resist degradation by the DPP-4 enzyme, maintaining its stability.

In April 2021, the semaglutide injection was approved in China for the treatment of type 2 diabetes. In the United States, the product has also been approved by the FDA to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease, as well as for the management of common obesity or overweight. Additionally, the product is currently undergoing a phase 3 international multicenter clinical trial for non-cirrhotic nonalcoholic steatohepatitis (NASH).

Novo Nordisk has launched a trial study in China, the EVOKE plus, to investigate the use of semaglutide in patients with early Alzheimer's disease. The aim is to confirm the superiority of oral semaglutide compared to placebo in terms of cognitive and functional changes in subjects with mild cognitive impairment (MCI) or mild dementia caused by Alzheimer's disease.

According to the information disclosed on the Chinadrugtrials website, this international multicenter Phase 3 clinical trial will be conducted across 436 institutions globally, with plans to enroll 115 participants in China and 1,840 participants internationally. In China, the principal investigator of this study is Professor Jia Jianping, Director Physician at Xuanwu Hospital, Capital Medical University.

Outside of China, Novo Nordisk announced in late 2020 the advancement of 14mg oral semaglutide into Phase 3 clinical trials for Alzheimer's disease. This decision was made following an evaluation of GLP-1 data from preclinical models, real-world evidence studies, post-hoc analyses of large cardiovascular outcome trial data, and discussions with regulatory authorities.

According to an earlier press release by Novo Nordisk, animal studies have highlighted the critical role of GLP-1 in relation to Alzheimer's disease, including improvements in memory function and reductions in phosphorylated tau protein accumulation. In particular, semaglutide has been shown to reduce neuroinflammation, which may impact cognition and function. Additionally, real-world evidence suggests a potential association between GLP-1 treatment and a reduced risk of dementia.

In a post-hoc analysis of data from three large cardiovascular outcome trials conducted on Novo Nordisk (LEADER, SUSTAIN 6, and PIONEER 6), which included 15,820 patients with type 2 diabetes with a median follow-up of 3.6 years, a total of 47 cases of dementia were identified, including 32 in the placebo group and 15 in the GLP-1 (liraglutide or semaglutide) group. The results showed that the incidence of dementia was statistically significantly reduced by 53% in patients taking GLP-1.

Note: The original text has been abridged.

References:

[1] Drug Clinical Trial Registration and Information Disclosure Platform. Retrieved Nov 2, 2021, from http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml

[2]Novo Nordisk to enter phase 3 development in Alzheimer’s disease with oral semaglutide . Retrieved Dec. 16，2020, from https://www.sec.gov/Archives/edgar/data/0000353278/000117184320008566/f6k_121620.htm

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