Sceptical American doctors are resisting prescribing the first drug that has been proved to slow the advance of Alzheimer’s – nine months after the US launch – posing an unexpected setback for Eisai and Biogen’s Leqembi.
Leqembi’s requirements, which include additional diagnostic tests, twice-monthly infusions and regular brain scans to guard against potentially lethal side effects, have contributed to slow adoption since the drug was approved by the US Food and Drug Administration, according to neurologists and geriatricians across 19 states.
But a number of them also say they have little faith in the medication, reports 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… that’s the problem,” said Dr James Burke, a neurologist at Ohio State University who has been an outspoken critic of Leqembi. “It’s certainly nothing like the home run we’re looking for.”
Another six scientists 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’ scepticism about 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 scepticism has hampered the launch, along with slower-than-expected adoption by large health systems.
He suggested 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 making more and more progress every month, so we’re still quite encouraged,” he said.
‘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 few thousand had begun treatment by the end of January.
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.
While the disease is estimated to affect more than 6m Americans, according to the Alzheimer’s Association, fewer than half of the country’s neurologists recommend Leqembi to patients.
Dr Michael Greicius, a professor at Stanford University’s Centre for Memory Disorders, said there was little evidence it benefited patients in a meaningful way.
“If we take the trial result at face value, the differences between placebo and treatment are probably small enough to be undetectable by patients and family 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, and significant costs, and I would say … marginal benefit,” said Dr Eric Widera, a geriatrician and professor at the University of California San Francisco, referring to amyloid-lowering treatments.
In an editorial in the Journal of Gerontological Nursing, Donna Fick, president of the American Geriatrics Society, said the group recommended caution in the use of lecanemab, 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.”
Ethical
Dr Nathaniel Chin, a geriatrician with the University of Wisconsin’s Alzheimer’s Disease Research Centre, 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 had 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?’”
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.
She said the companies are working with physician and patient advocacy groups and developing educational programmes 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 competitor Eli Lilly’s donanemab has been delayed until the FDA convenes an advisory panel.
Lilly neuroscience president Anne White said 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.
Journal of Gerontological Nursing article – Lecanemab – Shared decision-making (Open access)
Reuters article – Alzheimer’s drug adoption in US slowed by doctors’ scepticism (Open access)
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