Two New Alzheimer’s Drugs

Alzheimer’s is a progressive, degenerative and fatal brain disease, the most common cause of dementia. An estimated 6.7 million Americans age 65 and older are living with Alzheimer’s dementia. More than 11 million people act as caregivers of people with Alzheimer’s disease or other dementias.

The disease disrupts the communication among brain neurons, resulting in loss of function and cell death. The “amyloid hypothesis” suggests that a protein in the brain, amyloid, is a major contributor to the brain disorder. In Alzheimer’s disease, amyloid sticks together and forms clumps in the brain, which later become plaques. The damage to and eventual death of these brain cells leads to dementia.

While doubts have been cast on this hypothesis, based on one suspect study and after other amyloid drugs failed to help, the success of these two drugs lends support to the hypothesis.

Comparing the new Alzheimer’s drugs

Clinical trials demonstrate that removing amyloid from the brain provides measurable, meaningful benefit in people with early Alzheimer’s. Donanemab is designed to target plaques, and lecanemab is designed to remove plaques and to target other forms of amyloid. Both are administered in the early stages of the disease, when such delays are most valuable. Further delays in progression are anticipated with extended time under treatment.

Donanemab slowed the progression of Alzheimer’s by about 35%. Lecanemab reduced progression by about 27%. Neither of the drugs cures the disease. Instead, both decelerate progression of the disease in the early stages. Donanemab offers about a seven-month delay in the loss of memory and thinking skills. Leqembi delayed cognitive decline by 5.3 months.

Both of the two new Alzheimer’s drugs can cause dangerous swelling or bleeding in the brain.

Side effects of Leqembi include amyloid-related imaging abnormalities (ARIA), typically a temporary swelling and/or bleeding in certain areas of the brain that usually resolves over time. ARIA does not usually cause symptoms but in a low number of cases can be serious. In its approval, the FDA recommended, but did not mandate, genetic testing. People with two copies of a well-known Alzheimer’s risk gene may be more at risk of ARIA.

For donanemab, about 25% of patients experienced swelling or bleeding, seen in brain scans. About 6% had symptoms like headache, nausea, and confusion. Three patients died.

If approved, donanemab seems to have an edge over lecanemab. While Leqembi requires ongoing treatment, donanemab likely won’t. Patients stopped taking the drug once the plaques in their brains were mostly gone, usually within a year. The plaques did not reappear during the 18-month study, and the benefits were maintained. “I imagine in the future we’ll have this initiation phase where we knock down plaque and then we’ll have maintenance therapy,” Dr. Reisa Sperling of the Alzheimer Center at Brigham and Women’s Hospital in Boston told NPR.

While previous amyloid drugs seemed to lack efficacy, these new Alzheimer’s drugs are helping patients, probably because of earlier treatment, before significant brain damage has occurred, and with improvements in dosing. “We’ve learned to be more aggressive with dosing,” said Sperling, “which quickly reduces amyloid to very low levels in the brain.”

Related: Benefits of an early Alzheimer’s diagnosis

The Alzheimer’s Association on Leqembi approval

“This treatment, while not a cure, gives people in the early stages of Alzheimer’s disease more time to maintain their independence and do the things they love,” said Joanne Pike, Alzheimer’s Association president and CEO. “While we continue efforts to discover new targets and test new treatments, people living with this fatal disease deserve the opportunity to discuss and make the choice with their doctor if an FDA-approved treatment is right for them.”

The Alzheimer’s Association reminds people of the importance of an early diagnosis.

“An early and accurate diagnosis of Alzheimer’s has a positive impact on health outcomes, access to treatments, and eligibility for research trials, plus vital support and information services,” said Maria C. Carrillo, Alzheimer’s Association chief science officer.

Medicare coverage

Following the FDA decision, the Centers for Medicare & Medicaid Services (CMS) announced their plan to enable access to FDA traditionally approved Alzheimer’s treatments.

“CMS also said they will cover amyloid confirmation diagnostics, removing an obstacle to accurate diagnosis that far too many individuals have faced,” said Carrillo.

The announcement is an important development for people living with Alzheimer’s disease and their families.