Alzheimer’s Drugs Advance but Slowing Disease Remains a Challenge

But the drug’s benefit to patients may be limited, physicians and neurology researchers said. The reduction of cognitive decline that patients experienced was modest, they said, and might be too slight in some patients to justify potentially dangerous side effects. About 12% of patients who took lecanemab developed swelling and bleeding in the brain, Biogen and Eisai said.

“We still have the whole cliff to climb but at least now, we’re on the first ledge,” Robert Howard, a professor of old-age psychiatry at University College London, said of the lecanemab results.

Abnormal accumulations of beta-amyloid, called plaque, and tangles of another protein known as tau are characteristic features of the brains of people with Alzheimer’s. Researchers in the 1990s posited that a buildup of beta-amyloid was a primary cause of Alzheimer’s, prompting pharmaceutical companies to develop drugs aimed at clearing plaque. Drugs targeting beta-amyloid haven’t worked as well as researchers hoped.

“Scientifically, we see that busting amyloid plaques might make a small difference,” Dr. Howard said. “But unfortunately it’s not enough to make a significant difference in patients.”

Biogen and Eisai said they would release full data from lecanemab’s Phase 3 trial in November. The companies said any slowing of Alzheimer’s progression can be a benefit for patients given the progressive and deadly nature of the disease. Eisai has said the Food and Drug Administration is scheduled to decide whether to approve lecanemab in January.

Lecanemab is one of at least three drugs targeting beta-amyloid in development.

Roche Holding AG

said it would release Phase 3 results for its drug, gantenerumab, in the fourth quarter.

Eli Lilly

& Co. said it would release Phase 3 results for its drug, donanemab, next year.

Roche said that it was encouraged by the preliminary lecanemab data and that gantenerumab was a different molecule with unique mechanisms of action. Eli Lilly said the lecanemab results were clinically meaningful for the estimated 6.5 million people living with Alzheimer’s in the U.S., and said it was highly confident in donanemab’s potential to benefit patients.

Aducanumab, another Biogen-Eisai drug targeting plaque, last year became the first Alzheimer’s drug to be approved by the FDA in almost two decades.

But data from its Phase 3 trials wasn’t conclusive. After Medicare in April said it would deny routine payment for the drug, also known as Aduhelm, Biogen said it would stop marketing it.

In a recent meta-analysis of studies on Aduhelm, lecanemab and donanemab, French researchers found that while the drugs showed greater clinical benefit to patients with Alzheimer’s than placebo, the difference didn’t meet a threshold of clinical relevance.

That threshold was based on a 2019 study by researchers at Eli Lilly, who sought to quantify the minimum effect for an Alzheimer’s treatment to be considered clinically relevant, based on a dementia assessment known as CDR-SB. For patients with mild Alzheimer’s disease, a reduction of at least 0.98 points on a scale measuring cognitive decline would be considered clinically important, the authors concluded.

Nicolas Villain, an associate professor at Sorbonne University in Paris who was involved in the meta-analysis, said patients taking lecanemab experienced a reduction of 0.45 points on the CDR-SB scale, according to the preliminary Phase 3 data. Combining that data with other trials, Dr. Villain said the overall reduction on the CDR-SB scale for patients taking the anti-amyloid drugs as a whole was 0.31 points.

Biogen and Eisai said any reduction on the CDR-SB scale represented more time for an Alzheimer’s patient to live a fuller life. Citing earlier studies, an Eisai spokeswoman said a 20% to 30% slowing of cognitive decline based on the CDR-SB scale is considered clinically meaningful.

Based on hypothetical models, lecanemab could have more clinical benefit if used for longer periods, Dr. Villain said. He said the drug might be more beneficial in certain patients or in combination with other therapies.

“It’s not a miracle drug so far, but maybe it’s the beginning of something,” Dr. Villain said.

Researchers have said drugs targeting beta-amyloid could be more potent if administered early in the disease’s progression. It is possible the drugs could also be more effective in people with the APOE4 gene, which studies have shown increases the risk of developing Alzheimer’s. Researchers say more data is needed to know for sure.

Drugs that aim to stop Alzheimer’s in other ways are also in development. Some researchers are looking into whether traffic jams within endosomes, a type of specialized structure inside cells, or dysfunctional activity of cells called microglia could contribute to Alzheimer’s, among other possible risk pathways.

“We need to not just focus on amyloid plaque,” said Scott Small, director of the Alzheimer’s Disease Research Center at Columbia University and co-founder of a company developing an endosome-targeting drug to treat Alzheimer’s.

Write to Dominique Mosbergen at [email protected]

But the drug’s benefit to patients may be limited, physicians and neurology researchers said. The reduction of cognitive decline that patients experienced was modest, they said, and might be too slight in some patients to justify potentially dangerous side effects. About 12% of patients who took lecanemab developed swelling and bleeding in the brain, Biogen and Eisai said.

“We still have the whole cliff to climb but at least now, we’re on the first ledge,” Robert Howard, a professor of old-age psychiatry at University College London, said of the lecanemab results.

Abnormal accumulations of beta-amyloid, called plaque, and tangles of another protein known as tau are characteristic features of the brains of people with Alzheimer’s. Researchers in the 1990s posited that a buildup of beta-amyloid was a primary cause of Alzheimer’s, prompting pharmaceutical companies to develop drugs aimed at clearing plaque. Drugs targeting beta-amyloid haven’t worked as well as researchers hoped.

“Scientifically, we see that busting amyloid plaques might make a small difference,” Dr. Howard said. “But unfortunately it’s not enough to make a significant difference in patients.”

Biogen and Eisai said they would release full data from lecanemab’s Phase 3 trial in November. The companies said any slowing of Alzheimer’s progression can be a benefit for patients given the progressive and deadly nature of the disease. Eisai has said the Food and Drug Administration is scheduled to decide whether to approve lecanemab in January.

Lecanemab is one of at least three drugs targeting beta-amyloid in development.

Roche Holding AG

said it would release Phase 3 results for its drug, gantenerumab, in the fourth quarter.

Eli Lilly

& Co. said it would release Phase 3 results for its drug, donanemab, next year.

Roche said that it was encouraged by the preliminary lecanemab data and that gantenerumab was a different molecule with unique mechanisms of action. Eli Lilly said the lecanemab results were clinically meaningful for the estimated 6.5 million people living with Alzheimer’s in the U.S., and said it was highly confident in donanemab’s potential to benefit patients.

Aducanumab, another Biogen-Eisai drug targeting plaque, last year became the first Alzheimer’s drug to be approved by the FDA in almost two decades.

But data from its Phase 3 trials wasn’t conclusive. After Medicare in April said it would deny routine payment for the drug, also known as Aduhelm, Biogen said it would stop marketing it.

In a recent meta-analysis of studies on Aduhelm, lecanemab and donanemab, French researchers found that while the drugs showed greater clinical benefit to patients with Alzheimer’s than placebo, the difference didn’t meet a threshold of clinical relevance.

That threshold was based on a 2019 study by researchers at Eli Lilly, who sought to quantify the minimum effect for an Alzheimer’s treatment to be considered clinically relevant, based on a dementia assessment known as CDR-SB. For patients with mild Alzheimer’s disease, a reduction of at least 0.98 points on a scale measuring cognitive decline would be considered clinically important, the authors concluded.

Nicolas Villain, an associate professor at Sorbonne University in Paris who was involved in the meta-analysis, said patients taking lecanemab experienced a reduction of 0.45 points on the CDR-SB scale, according to the preliminary Phase 3 data. Combining that data with other trials, Dr. Villain said the overall reduction on the CDR-SB scale for patients taking the anti-amyloid drugs as a whole was 0.31 points.

Biogen and Eisai said any reduction on the CDR-SB scale represented more time for an Alzheimer’s patient to live a fuller life. Citing earlier studies, an Eisai spokeswoman said a 20% to 30% slowing of cognitive decline based on the CDR-SB scale is considered clinically meaningful.

Based on hypothetical models, lecanemab could have more clinical benefit if used for longer periods, Dr. Villain said. He said the drug might be more beneficial in certain patients or in combination with other therapies.

“It’s not a miracle drug so far, but maybe it’s the beginning of something,” Dr. Villain said.

Researchers have said drugs targeting beta-amyloid could be more potent if administered early in the disease’s progression. It is possible the drugs could also be more effective in people with the APOE4 gene, which studies have shown increases the risk of developing Alzheimer’s. Researchers say more data is needed to know for sure.

Drugs that aim to stop Alzheimer’s in other ways are also in development. Some researchers are looking into whether traffic jams within endosomes, a type of specialized structure inside cells, or dysfunctional activity of cells called microglia could contribute to Alzheimer’s, among other possible risk pathways.

“We need to not just focus on amyloid plaque,” said Scott Small, director of the Alzheimer’s Disease Research Center at Columbia University and co-founder of a company developing an endosome-targeting drug to treat Alzheimer’s.

Write to Dominique Mosbergen at [email protected]