Adoption of Alzheimer’s drug slowed
Doctors questioning treatment’s effectiveness
CHICAGO – Nine months into the U.S. 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 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.”
High risk, 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 that 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 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 a November editorial 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 received negative comments on social media after he urged geriatricians to embrace such treatments in the Journal of the American Geriatrics Society.
“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.