After weight loss, heart disease, and liver disease, can Sima still "resist dementia"? Novo Nordisk has "high hopes"

Since the launch of semaglutide seven years ago, Novo Nordisk's GLP-1 drug has expanded its applications from obesity and diabetes to heart disease and liver disease. Currently, Novo Nordisk is testing its efficacy for Alzheimer's disease.

This fall, Novo Nordisk will announce the clinical trial results of its GLP-1 drug semaglutide for the treatment of Alzheimer's disease. If the trial is successful, GLP-1 drugs could fundamentally change the treatment of Alzheimer's disease.

The research originated from an unexpected finding in Danish health registry data. Diabetic patients using Novo Nordisk's previous generation GLP-1 drug Victoza or similar medications had about a 20% lower risk of developing dementia compared to other treatment methods. This finding prompted Novo Nordisk to initiate a large-scale clinical trial targeting Alzheimer's disease.

UBS analysts estimate that the probability of Novo Nordisk succeeding in the Alzheimer's treatment field is only one in ten, but if successful, the company could gain an additional $15 billion in annual sales. Novo Nordisk's Chief Scientific Officer Martin Holst Lange stated:

We are excited about this, but we also believe it is a very, very high-risk project.

For Novo Nordisk, which is facing pressure from slowing growth, the success or failure of this investment is crucial. The company has downgraded its growth expectations twice this year, facing competition from compounding pharmacies selling cheaper similar drugs and from Eli Lilly's stronger products launched in the GLP-1 market.

Novo Nordisk's stock price has fallen over 58% in the past 12 months, far exceeding Eli Lilly's 23% decline. However, analysts believe that even if Novo Nordisk's research fails, academic research on GLP-1 drugs in the field of Alzheimer's disease will continue.

(Novo Nordisk's U.S. stock price has fallen over 58% in the past 12 months)

Disrupting Traditional Treatment Mechanisms

Currently approved Alzheimer's disease drugs primarily work by combating amyloid proteins, which are toxic misfolded proteins that accumulate in the brains of Alzheimer's patients.

The treatment concept of semaglutide is entirely different; it mimics an intestinal hormone called GLP-1, and researchers believe the drug may work by reducing inflammation and altering brain glucose metabolism.

Multiple studies have shown that diabetic patients are more likely to develop dementia, providing a reasonable explanation for the association between the two. Howard Fillit, co-founder and Chief Scientific Officer of the Alzheimer's Drug Discovery Foundation, stated that if the trial is successful, semaglutide will "become one of the first anti-aging drugs."

Michal Schnaider Beeri, director of the Alzheimer's Disease Research Center at Rutgers University, stated:

If they can prove something, that would be amazing. I am very hopeful.

Real-World Challenges in Trial Design

Despite the promising outlook, Alzheimer's disease is recognized as a "no-go zone" in drug development, with hundreds of hopeful studies ultimately ending in failure.

The design of this trial itself also presents challenges. Jared Holz, a healthcare industry strategist at Mizuho Securities, pointed out that conducting preventive trials in healthy volunteers is "costly and operationally complex."

Therefore, Novo Nordisk chose to test whether the drug can delay the progression of the disease in mild patients who have already been detected with amyloid proteins in the brain. Holz added:

Many of the challenges in Alzheimer's clinical trials stem from the fact that by the time treatment begins, the patient's condition may have already progressed to a relatively late stage.

However, he added that even if the research results show only slight benefits, some individuals may begin to take semaglutide as a preventive measure.

Currently approved Alzheimer's drugs, such as those from Eisai and Eli Lilly, primarily slow the progression of the disease by clearing toxic β-amyloid plaques from the brain, but their effects are limited and come with risks of serious side effects such as brain hemorrhage