Although Aduhelm stumbled, Leqembi has received full FDA approval, and Eli Lilly has reported positive results for donanemab.
Alzheimer’s disease is the most common type of dementia, affecting more than 6 million people in the United States. According to the Alzheimer’s Association projection, by 2050 Alzheimer's disease is expected to rise to about 13 million, incurring just over $1 trillion each year in national costs.
Until recently, drugs approved to treat patients with Alzheimer’s disease only addressed its symptoms. The FDA approved Biogen’s Aduhelm (aducanumab) in 2021, via the accelerated approval program. Aduhelm was the first FDA-approved amyloid beta-directed antibody designed to remove beta-amyloid plaques from the brain and potentially affect disease progression. But Aduhelm became bogged down in controversy, and the Centers for Medicare & Medicaid Services limited coverage to people enrolled in a clinical trial. The drug has not received full FDA approval.
Biogen Inc. has gone on to partner with Japanese drug manufacturer Eisai Co., Ltd., to develop a second amyloid beta-directed antibody for treating patients with Alzheimer’s. Leqembi (lecanemab) was initially granted accelerated approval in January 2023; in July 2023, it became the first in its class to receive full traditional FDA approval.
That approval was based on results from the confirmatory phase 3 trial CLARITY AD. In the study, 1,795 adults with mild cognitive impairment or mild dementia due to Alzheimer’s disease were randomly assigned to receive Leqembi or placebo. The study met its primary end point of statistically significant reduction in cognitive decline at 18 months versus placebo, as well as a significant decrease in amyloid burden in the Leqembi group compared with the placebo group.
Common side effects included amyloid-related imaging abnormalities (ARIA), a temporary swelling or bleeding in parts of the brain. These changes are typically asymptomatic but can be more serious.
Eli Lilly and Company also had a win earlier in 2023, announcing positive results of the phase 3 TRAILBLAZER-ALZ 2 trial, which investigated the use of donanemab, an amyloid-targeting antibody designed to remove amyloid plaques, in patients with early Alzheimer’s disease.
The study enrolled 1,736 individuals with mild cognitive impairment or mild dementia due to Alzheimer’s and amyloid and tau protein pathology. Patients were randomly assigned to receive donanemab placebo for up to 72 weeks. In the trial, 47% of patients who received donanemab showed no signs of disease progression at one year compared with 29% of those receiving placebo. Donanemab slowed clinical decline by 35% and led to a 40% reduction in declining ability to perform activities of daily living.
Positive effects were observed throughout the trial duration, even though many study participants had completed their treatment at six or
12 months. Investigators suggest these results may support limited-duration dosing, reducing treatment costs and other burdens associated with treatment. ARIA was a common side effect in participants taking donanemab.
Based on these encouraging results, the company has filed for FDA approval and expects a regulatory decision by the end of the year.
Clinicians currently use cognitive exams, such as the Mini-Mental Srate Exam, along with PET scans and spinal taps to withdraw cerebrospinal fluid, to diagnose Alzheimer's disease.
There is ongoing research to develop less invasive blood tests to detect amyloid or tau protein pathology. For example, ALZpath, a California-based developer of Alzheimer’s diagnostic tools, recently received funding from the Alzheimer’s Drug Discovery Foundation to advance ALZpathDx, a blood-based test that measures tau protein.
Rosanna Sutherby, Pharm.D., is an independent medical writer and community pharmacist in High Point, North Carolina, and a regular contributor to Managed Healthcare Executive.