Eli Lilly’s Alzheimer’s therapy, donanemab, has received FDA approval, offering new hope for patients with early symptomatic Alzheimer’s disease. The newly approved treatment, branded Kisunla, is set to challenge existing therapies from Eisai and Biogen. 

Clinical trials have shown Kisunla to be effective for individuals in the mild cognitive impairment or mild dementia stages of the disease, potentially marking a significant advancement in Alzheimer’s care.

The drug is administered as an intravenous infusion every four weeks. 

Alzheimer’s disease is a degenerative condition of the brain that impacts over 6.5 million Americans and over 55 million people worldwide. It causes a gradual decline in memory, cognitive functions, and, eventually, the ability to perform daily activities. The disease is marked by structural changes in the brain, such as the buildup of amyloid beta plaques and neurofibrillary tangles made of tau protein, which is supposed to help stabilize the internal skeleton of neurons in the brain. 

The Alzheimer’s Association celebrated the FDA’s decision.

“This is real progress,” said Joanne Pike, Alzheimer’s Association president and CEO, in a statement. “Today’s approval allows people more options and greater opportunity to have more time. Having multiple treatment options is the kind of advancement we’ve all been waiting for — all of us who have been touched, even blindsided, by this difficult and devastating disease.”

Slows cognitive decline by at least 22%

The approval was based on an extensive double-blind, placebo-controlled, parallel-group study evaluating the efficacy of Kisunla in slowing cognitive decline in participants with varying levels of tau protein in the brain. Tau is a protein that helps to stabilise the neurons in the brain. 

The study, conducted over 72 weeks with 1,736 patients averaging 73 years old, revealed that those receiving Kisunla experienced a 35% reduction in cognitive decline compared to those on placebo among individuals with low to medium tau levels. 

Even among participants with higher tau levels, the treatment demonstrated a meaningful but slightly reduced effect. Overall, including all tau levels, Kisunla slowed cognitive decline by 22% and reduced the likelihood of progressing to the next stage of the disease by 39% compared to placebo.

Additionally, the study monitored amyloid plaque levels using positron emission tomography (PET) scans throughout the treatment period. Results showed substantial reductions in amyloid plaques over time among patients receiving Kisunla, with reductions of 61% at six months, 80% at 12 months, and 84% at 18 months compared to baseline levels. These findings suggest that Kisunla not only targets cognitive decline but also effectively reduces the hallmark amyloid pathology associated with Alzheimer’s disease progression.

Potential side effects

For some patients, there is a risk of amyloid-related imaging abnormalities (ARIA) developing, the FDA said. ARIA typically manifests as temporary brain swelling, sometimes accompanied by small areas of bleeding on or in the brain. While ARIA often resolves on its own and may not cause symptoms, rare instances of severe and potentially life-threatening events have been reported. ARIA is a recognized side effect of antibody therapies targeting amyloid.

Infusion-related reactions are also a concern, including flu-like symptoms, nausea, vomiting, changes in blood pressure, and hypersensitivity reactions such as anaphylaxis (a severe allergic reaction) and angioedema (swelling). 

Kisunla joins Leqembi, on market since 2023

Kisunla is the third drug to receive FDA approval, although only the second is now available for use. Leqembi, a collaboration between Biogen of the United States and Eisai of Japan, gained approval in July 2023. In an 18-month Phase III trial, Leqembi demonstrated a 27% reduction in cognitive decline among early-stage Alzheimer’s patients compared to those receiving a placebo.

Another drug, aducanumab, also developed by Biogen and Eisai, was granted accelerated approval by the FDA in June 2021. However, due to some side effects, the therapy was pulled from the market. 

The Alzheimer’s Association emphasized the importance of early detection and diagnosis now that multiple FDA-approved treatments for Alzheimer’s are available. The organization stressed that timely access to these treatments is crucial for maximizing their benefits, asserting that no stage or entity should hinder or delay such access.

“Too many roadblocks have prevented individuals from getting equitable access to these beneficial treatments for far too long,” said Pike. “It is equally important that clinicians and health care systems are informed and prepared to help the individuals who could benefit. The Alzheimer’s Association is working with health systems and providers to ensure they have the tools and resources to meet the needs of their patients.”

Image Credits: Gerry Shaw/ EnCor Biotechnology Inc.