The pharmaceutical companies said their drug lecanemab reduced cognitive and functional decline by 27%, compared with a placebo, over 18 months in a Phase 3 study of 1,800 patients with early-stage Alzheimer’s. The drug was also linked to higher rates of brain swelling and small bleeds, though the company said they were rarely symptomatic.
“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said Biogen Chief Executive
The trial data were disclosed by Japan’s Eisai in a press release, and haven’t been published in a peer-reviewed medical journal. The company said it would present more detailed study results in November at an Alzheimer’s research conference and publish the results in a peer-reviewed journal.
“These data are compelling,” said Richard S. Isaacson, director of the Center for Brain Health at Florida Atlantic University, though he said he wants to review the full trial results once they are published. “But in the right patient population at the right time and the right dose, this is a treatment that will probably become a part of the standard of care for patients.”
The U.S. Food and Drug Administration is already reviewing whether to grant conditional early approval to lecanemab based on the drug’s ability to reduce deposits of the amyloid-beta protein, which builds up in the brains of people with Alzheimer’s, in a mid-stage, or Phase 2, study. The regulator is scheduled to make an approval decision by Jan. 6, Eisai said earlier this year.
The new Phase 3 study results disclosed on Tuesday are intended to prove that reducing amyloid results in a slower decline in cognitive function from Alzheimer’s. Eisai, which is leading the drug’s clinical development and regulatory process, said it would use the data to ask for full approval in the U.S., Europe and Japan by the end of March.
The “study results prove the amyloid hypothesis, in which the abnormal accumulation of [amyloid-beta] in the brain is one of the main causes of Alzheimer’s disease,” said Eisai Chief Executive
The late-stage study has been eagerly anticipated by researchers and investors as the first big test for a promising class of Alzheimer’s drugs that lost luster after the failed launch of Aduhelm, which was also developed by Eisai and Biogen. Like Aduhelm and other drugs, lecanemab is designed to reduce amyloid deposits, which have been linked to Alzheimer’s, though its precise role in driving the disease, if any, is still debated.
In the Phase 3 study, 21.3% of patients receiving lecanemab experienced brain swelling, bleeding or both, compared with 9.3% in the placebo group. The side effects are linked to drugs that target brain amyloid and are usually detected during routine trial monitoring using magnetic resonance imaging scans, or MRIs, of patients’ brains.
Eisai said the rates of brain amyloid-related side effects were within its expectations, and that 2.8% of lecanemab patients experienced symptoms related to brain swelling, and 0.7% had symptoms from brain bleeding. Doctors have said the side effects are manageable with close monitoring, though patients in the real world might not receive as much attention from doctors as they would in clinical trials.
Last year, Aduhelm became the first new Alzheimer’s treatment approved by the FDA in nearly two decades. But the drug’s commercial prospects were doomed by a Medicare decision in April to refuse routine coverage of it, effectively cutting off access to the most of Alzheimer’s patients in the U.S.
Eisai surrendered its right to share in Aduhelm’s profits after Medicare first proposed denying coverage, and Biogen said in May that it would stop marketing it.
Medicare’s unusual decision to deny routine payment for an approved medicine followed criticism of the FDA’s decision to approve Aduhelm despite objections by outside advisers and other scientists that it hadn’t yet proved to work.
The FDA granted Aduhelm under accelerated approval, a regulatory designation that allows the agency to clear medicines for serious, life-threatening diseases based on indirect measures of disease likely to improve patients’ symptoms. In Aduhelm’s case, the FDA said for the first time that it considered amyloid reduction as a likely predictor of slower decline from Alzheimer’s, which some doctors criticized because the drug had failed to show a statistically significant improvement in patients’ disease progression in clinical trials.
Medicare’s policy requires that anti-amyloid drugs approved under accelerated approval only be covered for patients enrolled in randomized clinical trials that meet certain criteria approved by government officials. Patients taking drugs with full FDA approval will also have to enroll in studies, but with less stringent criteria that are aimed at tracking side effects and other outcomes over time.
Eisai said in July that the FDA had accepted its application to consider accelerated approval of lecanemab.
& Co.’s anti-amyloid drug donanemab is also being reviewed for accelerated approval, and the FDA is scheduled to make a decision in early January, a Lilly spokeswoman said. Lilly’s Phase 3 confirmatory study of the drug is expected to have results in mid-2023, the spokeswoman said.
Eisai’s Phase 2 study failed to reach its primary goal of showing a 80% probability of slowing patients’ cognitive decline, compared with a placebo; the drug showed a 64% probability. However, lecanemab did reduce brain amyloid that was linked to slower clinical decline, researchers said.
An estimated six million people in the U.S. suffer from Alzheimer’s, and about two million of those were thought to potentially benefit from Aduhelm because they had early-stage disease and brain amyloid, Biogen has said.
Currently available treatments help temporarily alleviate some of the symptoms of Alzheimer’s, but none affect the overall course of disease. The most common Alzheimer’s drug taken by Medicare patients is Eisai’s Aricept, which is also available as a generic.
Write to Joseph Walker at firstname.lastname@example.org
Copyright ©2022 Dow Jones & Company, Inc. All Rights Reserved. 87990cbe856818d5eddac44c7b1cdeb8