The Food and Drug Administration on Friday approved a new Alzheimer’s disease treatment that moderately slows cognitive decline in people with early-stage disease.
The drug, called Leqembi, was developed by Eisai, the Japanese pharmaceutical company that also developed the first symptomatic treatment for Alzheimer’s 25 years ago.
Leqembi will cost $26,500 per year for a person of average weight, Eisai said. The drug has the potential to be a commercial blockbuster, but only if Medicare can be convinced to pay for it. Unless Medicare changes the way it pays for drugs like Leqembi, Eisai expects a relatively slow rollout.
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“The U.S. is the first regulatory approval of Leqembi globally and represents a major yet humble achievement in our decades of research in Alzheimer’s,” said Ivan Cheung, chairman of Eisai’s U.S. operations and global head of its Alzheimer’s unit.
Biogen, the Cambridge, Mass.-based biotech, will co-market the drug with Eisai under a long-standing partnership. For Biogen, the new drug is an opportunity to reverse a decline in its business and repair its reputation following the widely rebuked approval and failed launch of Aduhelm, its previous Alzheimer’s treatment.
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Alzheimer’s experts said Leqembi, previously known by its scientific name lecanemab, provides modest benefits for patients with mild cognitive impairment or early stage Alzheimer’s. It carries some risks for swelling and bleeding in the brain that will require monitoring. But Alzheimer’s hasn’t seen real medical progress in decades, so even with limitations, the drug is groundbreaking and a reason for cautious optimism.
“I’ve made this diagnosis thousands of times. I’ve held a lot of hands and passed a lot of Kleenex,” said Jo Cleveland, a physician and professor specializing in geriatric medicine at Wake Forest Baptist Health. The new approval “feels like the beginning of something important, like maybe now we can get some momentum.”
Although Leqembi is not a cure for Alzheimer’s, a large clinical trial published in November showed the treatment slowed the cognitive and functional decline of patients with early-stage Alzheimer’s by 27% relative to placebo. In the 18-month study, Eisai’s drug also dramatically reduced levels of beta-amyloid, a toxic protein in the brain thought to drive the advance of Alzheimer’s.
Leqembi is administered via an intravenous infusion every two weeks.
Technically, the FDA granted accelerated approval to Leqembi, a faster path to the market based on preliminary evidence that the drug eliminates toxic amyloid. It’s the same controversial, regulatory shortcut that the FDA used to approve Aduhelm. But unlike Biogen, Eisai within days is expected to submit the cognition data from its positive, confirmatory study to the FDA, which will then consider the drug for full, or final, approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” said Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”
Eisai restricted the study of Leqembi to people with mild cognitive impairment or early stage Alzheimer’s that also have evidence of amyloid buildup in the brain, confirmed by an imaging scan. The FDA-approved label reflects the same narrowed patient population, estimated to encompass approximately 1 million people in the U.S., or just under 20% currently living with an Alzheimer’s diagnosis.
The label also mandates that patients undergo three additional brain scans during the first 14 weeks of treatment as a precautionary step to monitor for potentially serious brain swelling or bleeding episodes.
Although most occurrences of this common side effect, called ARIA, can be managed without complications, it is amplified in people taking concomitant blood-thinning medications to prevent clots, and has been associated with at least two deaths, including one first reported by STAT. A case study detailing the second patient death was published this week in the New England Journal of Medicine. Eisai has said that the rate of ARIA reported in its Leqembi studies is low and that independent safety monitors have not raised any concerns.
The FDA, in the prescribing label, advised physicians to take “additional caution” when considering the use of Leqembi in people who are also prescribed so-called antithrombotic medications.
Eisai is funding several programs to educate and train physicians about the diagnosis and treatment of ARIA-related side effects. “We are committed to understanding ARIA, proactively,” said Cheung.
Luca Giliberto, a neurologist and professor at Northwell Health’s Feinstein Institutes for Medical Research on Long Island, NY, said his institution’s dementia steering committee is likely to endorse the use of Leqembi, but with conservative screening guidelines that exclude people at risk of bleeding or with the presence of microhemorrhages.
“I think there is a subset of patients that will benefit from the drug,” he said. “The effect size is minimal and may not be perceptible to patients or caregivers over the 18 months shown in the trial. But if you continue treatment long enough — two years or more — maybe the difference will improve.”
Madhav Thambisetty, a neurologist and an adjunct professor of neurology at Johns Hopkins University School of Medicine, said “real-world” use of Leqembi should “resemble those enrolled in the Phase 3 study as closely as possible.”
Some data from Eisai’s clinical trial suggested that approximately 10% of people who carry two copies of APOE4, the most common genetic risk factor for Alzheimer’s, don’t benefit from Leqembi and may actually be harmed by it. This is an “overlooked” risk and an “unprecedented challenge,” Thambisetty added, because genotyping for APOE4 status is not standard practice for physicians who diagnose and treat people with Alzheimer’s.
Eisai has downplayed these findings, arguing the statistical evidence is weak. The FDA did not include any language in the Leqembi prescribing label that restricts use of the drug based on APOE4 status.
Ian Grant, assistant professor of neurology at Northwestern University Feinberg School of Medicine, said Leqembi has a “real but marginal benefit” that will make a meaningful difference for some of his patients. Others may not notice any improvement.
“I don’t want to impose what I think is clinically meaningful on my patients and their families. Anything that provides some benefit, no matter how small, is worth it to [some patients]. Others may see it differently,” he said.
Cleveland, the Wake Forest physician, estimates that 10%-15% of the people coming to her clinic for a cognitive assessment would likely be good candidates for Leqembi.
“I will prescribe it for the right patient. I think that person is somebody who’s pretty physically healthy, who has mild cognitive impairment or very early Alzheimer’s disease, with documented amyloid in the brain and probably isn’t on a blood thinner,” she said, adding there will “controversy” in the field over whether Leqembi should be contraindicated for people on antithrombotic medicines.
Eisai has the final decision-making power on all matters — scientific and business — related to Leqembi. And with that authority, the company appears cognizant that overcoming the challenges of marketing an Alzheimer’s drug starts with avoiding the mistakes made by Biogen when it launched Aduhelm.
At $26,500 per year for an average patient, Leqembi is priced in a way that makes out-of-pocket costs for patients manageable, and ensures “the health system and the Medicare system are sustainable,” said Eisai’s Cheung.
When mandatory government rebates are factored in, Eisai believes half of the drug’s “quantified value” — estimated by the company at $37,000 per year — will be given back to society, Cheung added.
The initial price selected for Leqembi is considerably less than the $56,000 chosen by Biogen for Aduhelm, which was later halved to $28,000 following a firestorm of criticism. Last week, congressional investigators issued a report that lambasted Biogen for trying to maximize its profits at the expense of taxpayers and Alzheimer’s patients.
In a recently issued report, the Institute for Clinical and Economic Review, a drug-pricing analysis group, concluded Leqembi was cost-effective if priced between $8,500 and $20,600 per year.
Leqembi will be available to physicians starting the week of Jan. 16, Eisai said, although without Medicare reimbursement coverage, the company expects immediate use to be minimal.
“In this initial phase, our goal is not to ramp up sales, but to get the healthcare system ready, while simultaneously working with [Medicare] to lift its restrictions,” said Cheung.
After three years, Eisai estimated that 100,000 people might be prescribed Leqembi, with patient numbers potentially growing as the company develops a new formulation that can be injected just under the skin, and as additional studies investigating the drug in combination with other medicines read out results.
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