Alzheimer's drug adoption in US slowed by doctors' skepticism

Nine months into the US launch of the first drug proven to slow the advance of Alzheimer's, Eisai 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 US 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 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 announced only a couple thousand had begun treatment as of the end of January. An Eisai 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 US 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 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 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."