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By Julie Steenhuysen

CHICAGO, April 23 (Reuters) - Nine months into the U.S.

launch of the first drug proven to slow the advance of

Alzheimer's, Eisai ( ESALF ) and Biogen's Leqembi is facing an unexpected

hurdle to widespread use: an entrenched belief among some

doctors that treating the memory-robbing disease is futile.

Alzheimer's experts had anticipated bottlenecks due to

Leqembi's requirements, which include additional diagnostic

tests, twice-monthly infusions and regular brain scans to guard

against potentially lethal side effects.

And those issues have played a role in slow adoption since

the drug was approved by the U.S. Food and Drug Administration,

according to interviews with 20 neurologists and geriatricians

from rural, urban, academic and community practices in 19

states.

In interviews with Reuters, seven doctors treating patients

for Alzheimer's attributed their own reluctance to prescribe

Leqembi to concerns about the drug's efficacy, cost and risks.

"I don't think it's a good Alzheimer's drug. I think that's

the problem," said Dr. James Burke, a neurologist at the Ohio

State University who has been an outspoken critic of Leqembi.

"It's certainly nothing like the home run that we're looking

for."

Another six scientists, all leaders in the field, said

"therapeutic nihilism" - the belief that Alzheimer's is a

hopelessly intractable disease - was playing a bigger role than

anticipated in suppressing demand from primary care doctors,

geriatricians and neurologists who could be sending patients to

memory specialists for treatment.

Dr. Reisa Sperling, a neurologist and Alzheimer's researcher

at Mass General Brigham in Boston, likens some doctors'

skepticism to Leqembi to fatalistic attitudes about cancer

treatment 30 years ago: "You can't really do anything about it,

so why would you even want to get tested?"

Alex Scott, Eisai's ( ESALF ) chief administrative officer,

acknowledged that skepticism has weighed on the launch along

with slower-than-expected adoption by large health systems.

He suggested that some of the doctors' hesitancy could be a

holdover from the decades-long journey to prove that removing

the Alzheimer's protein beta amyloid from the brain could slow

the course of the disease. Before Esai released the promising

results of its Leqembi trial, some thought that area of research

"a fool's errand," Scott said.

"We are beginning to make more and more progress every

single month. So we're still quite encouraged," Scott said.

"This is a new journey, and I think it takes some time for

providers to figure it out."

'SIGNIFICANT RISKS, MARGINAL BENEFIT'

Leqembi was the first amyloid-targeting drug granted full

FDA approval after it slowed the decline in cognition in people

in the early stages of Alzheimer's by 27% in a clinical trial.

Of the 10,000 Americans the companies hoped to treat by the

end of March, Eisai ( ESALF ) announced only a couple thousand had begun

treatment as of the end of January. An Eisai ( ESALF ) spokeswoman

declined to provide updated numbers.

Even for treatments that do not require dramatic changes to

medical practice, adoption of new drugs is notoriously slow.

Several studies have estimated that it can take 17 years on

average for clinical research to be translated into routine

practice.

The disease is estimated to affect more than 6 million

Americans, according to the Alzheimer's Association.

Fewer than half of U.S. neurologists recommend Leqembi to

patients, according to a January survey by life sciences market

researcher Spherix Global Insights.

Dr. Michael Greicius, a professor at Stanford University's

Center for Memory Disorders, said there is little evidence that

Leqembi benefits patients in a meaningful way.

"If we take the trial result at face value, the differences

between placebo and treatment are likely small enough as to be

undetectable by patients and family members or physicians," said

Greicius, who does not recommend Leqembi to patients.

He said the long wait for an Alzheimer's drug has put

doctors in the position of feeling obligated to offer a

treatment "even if the evidence for it is very slim."

Other doctors have raised concerns about the risk of brain

swelling and bleeding associated with Leqembi as well as the

costs associated with the $26,500 annual drug, frequent MRIs and

twice-monthly infusions.

"There are significant risks associated with these drugs,

there are significant costs, and I would say there is marginal

benefit," said Dr. Eric Widera, a geriatrician and professor at

University of California San Francisco, referring to

amyloid-lowering treatments.

In an editorial published in November in the Journal of

Gerontological Nursing, Donna Fick, president of the American

Geriatrics Society, advised doctors that the group recommends

caution in the use of lecanemab, which is sold under the brand

name of Leqembi.

"It is not yet clear whether treatments such as lecanemab

that remove amyloid from the brain produce clinically important

slowing of cognitive decline in Alzheimer's disease."

'YOUR ENEMY IS NIHILISM'

Dr. Jonathan Liss, a neurologist from Columbus, Georgia, who

serves on Eisai's ( ESALF ) scientific advisory board and has tested

Leqembi in clinical trials, said he first warned about nihilism

at a November 2022 conference following a presentation of

Leqembi's breakthrough study.

Eisai ( ESALF ) had asked its scientific advisors how the drug might

fare against future rivals. Liss cautioned that rivals were not

the enemy; "your enemy is nihilism,'" he recalled. "All of the

neurologists around the table started applauding."

Dr. Nathaniel Chin, a geriatrician with the University of

Wisconsin's Alzheimer's Disease Research Center, said he was the

target of negative comments on social media after he urged

geriatricians to embrace such treatments in the Journal of the

American Geriatrics Society.

Geriatricians, geriatric social workers and nurses objected,

arguing that the drug's statistically significant benefit was

not clinically meaningful to patients, especially given the

risks, he said.

"I would ask the question, 'Is it ethical to withhold a

medication that is FDA-approved and covered by insurance from

someone who knows the risk and is willing to take it?'" Chin

said.

Dr. Priya Singhal, executive vice president and head of

development at Biogen, acknowledged some apathy among

physicians about the treatment but said that infrastructure and

lack of access to neurologists have been bigger issues.

Singhal said the companies are working with physician and

patient advocacy groups and developing educational programs and

materials aimed at diagnosing early-stage patients, managing

side effects and understanding the drug's benefits.

The companies said they intend to increase their salesforce

by 30% as they aim for 100,000 patients by 2026.

For the moment, Leqembi is the only Alzheimer's drug on the

market designed to slow the course of the disease. A decision on

Lilly's donanemab has been delayed until the FDA

convenes an advisory panel.

Lilly neuroscience president Anne White said in an interview

that she sees doctor hesitancy as an issue that the company

hopes to address by making clear which patients benefit from

such treatments.

In the early stages of Alzheimer's, many patients are still

independent, and to be able to remain so for longer is very

meaningful, she said.

'PEACE AND QUIET'

Lyn Castellano, 64, who founded and ran a St. Louis breast

cancer charity for 20 years and trained therapy dogs, started

taking Leqembi last September, nearly a year after she found

herself struggling with keeping track of appointments and was

diagnosed with mild cognitive impairment.

Castellano said the prospect of bleeding in the brain - a

possible side effect of the drug - was her biggest concern, but

her family believed the drug may offer a chance at slowing the

disease.

She is one of more than 140 patients being treated by

physicians from Washington University in St. Louis, and has had

13 infusions and two MRIs without incident.

Dr. Suzanne Schindler, an Alzheimer's researcher who is

treating Castellano, said Leqembi "forces clinicians to

completely change the way they have practiced medicine for many

years."

She said she is candid about Leqembi's modest benefit as

well as the risks. About 80% of those she believes are good

candidates have opted for the treatment, she said.

While Castellano can't tell if Leqembi is helping, she says

the treatment has given her hope, and she doesn't mind the twice

monthly infusions.

"I get to go, sit back in a nice chair, have my dog with me

and read a book for a couple hours. It's about the only place I

get some peace and quiet."