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Novo trials test Rybelsus for Alzheimer's cognitive

decline

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Experts uncertain on GLP-1 impact on Alzheimer's brain

pathology

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Success could boost Novo shares by up to 10%, analysts say

By Deena Beasley and Julie Steenhuysen

Nov 20 (Reuters) - Studies from Novo Nordisk

due early next month will give the strongest indication yet of

whether blockbuster GLP-1 drugs - a class being used by millions

for diabetes and weight loss - can slow progress of Alzheimer's

disease.

Two trials, described by Novo as a "lottery ticket," are

testing its older diabetes pill Rybelsus that has the same

active ingredient - semaglutide - as Ozempic and Wegovy in

thousands of people with mild Alzheimer's. The goal is to

decrease patients' rate of cognitive decline by at least 20%.

Alzheimer's experts say success would usher in a convenient

new treatment to slow progression of the mind-robbing disease

defined by toxic amyloid plaques in the brain that affects 50

million people globally.

Regardless of the results, researchers expect to glean

important clues for future study into how and why these types

of drugs, which include Eli Lilly's ( LLY ) Zepbound and

Mounjaro, may be useful against the disease.

"It really has a chance to be transformational," Alzheimer's

Association Chief Science Officer Maria Carrillo said.

She and other Alzheimer's experts told Reuters it's not

clear how drugs that target the GLP-1 receptor impact the brain.

Most of the evidence going into the trials supported the use

of GLP-1s in patients who have dementia associated with diabetes

and obesity.

The Alzheimer's studies were launched in 2021 based on

animal evidence and analysis of human studies showing a reduced

risk of dementia or Alzheimer's in diabetes patients treated

with GLP-1s, a Novo spokesperson said. A small study of the

company's older injectable GLP-1, liraglutide, found it slowed

the loss of brain volume in people with mild Alzheimer's.

AFFECT ON BRAIN UNCLEAR

About 60% of dementia patients have Alzheimer's, while the

remainder have diseases like vascular dementia, caused by

blocked blood flow to the brain. Many have more than one type of

dementia.

Because the trials required all participants to have

confirmed Alzheimer's disease, it was difficult to recruit

patients who also had vascular dementia - common in people with

diabetes - because their condition was too advanced to qualify,

said Dr. Mary Sano, a Mount Sinai Alzheimer's researcher and

investigator on the studies.

Scientists said it remains unclear how GLP-1s in prior

studies reduced the risk of dementia. The drug may have had a

direct effect in the brain or improvements such as weight loss

or reduced inflammation in the body may protect the brain.

And not all GLP-1s are the same. Studies in mice suggest

liraglutide, sold as Victoza and Saxenda, can enter the brain

more easily than semaglutide, said Dr. Heather Ferris, an

endocrinologist at the University of Virginia.

Ferris is expecting "positive, but paltry positive results"

from the Novo studies.

Dr. David Knopman, a neurologist at the Mayo Clinic in

Rochester, Minnesota, said it is "totally unknown what the link

is between the GLP-1 target in the brain and Alzheimer's

pathology, and that is not a good sign."

There are currently two drugs approved for slowing

Alzheimer's by removing amyloid from the brain, Lilly's Kisunla

and Leqembi from Eisai ( ESALF ) and Biogen. They are

given as infusions or injections and were shown in clinical

trials to slow disease progression by close to 30%.

They also carry the risk of serious side effects and require

regular scans.

RESULTS MAY GUIDE FUTURE TRIALS

Dr. Howard Fillit of the Alzheimer's Drug Discovery

Foundation, which funds Alzheimer's research including the

liraglutide study, said Novo's trials could shed light on the

impact of GLP-1s on age-related changes to brain metabolism that

occur before the formation of amyloid plaques.

The studies would be considered clear successes if Rybelsus

slows cognitive decline by close to 30%, he said.

If not, the results could help guide future trial design,

including potential combinations of GLP-1s with existing

Alzheimer's drugs, Fillit said.

Lilly said it continues "to closely monitor the evolving

science to better understand" the role of GLP-1s in brain

health.

Lilly is currently studying whether Kisunla can prevent

Alzheimer's before symptoms arise. That trial is due to conclude

in 2027. Eisai ( ESALF ) and Biogen are conducting a similar study of

Leqembi. Eisai ( ESALF ) said in a statement that if the Novo trials show

a significant clinical benefit, semaglutide may be complementary

to a drugs like Leqembi.

SUCCESS COULD LIFT NOVO SHARES

If Rybelsus slows cognitive decline in early Alzheimer's, it

would be safer and more convenient than amyloid-lowering drugs,

experts said. Still, Rybelsus can be challenging as it needs to

be taken on an empty stomach, 30 minutes before eating,

drinking, or using any other oral medication.

Clear success could bump up Novo's shares by as much as 10%,

while a failure could cause them to slump by 5%, Wall Street

analysts predicted.

Novo is slated to present its results on December 3 in San

Diego at the Clinical Trials on Alzheimer's Disease meeting,

although it could announce some data before then.

"An oral medication that was safe is a big deal in terms of

marketability. There will be a very low threshold for a drug

like that," Knopman said.