Dementia is a disease that affects women more than anyone else: In fact, approximately twice as many women are diagnosed with Alzheimer’s disease, the most prevalent form of dementia, compared to men. However, there has been immense progress in early detection and personalized treatments that pave the way for more effective management of this disease. In a groundbreaking move, the FDA has approved a new drug, Kisunla (donanemab-azbt) which is a once-a-month injectable treatment for those with early symptomatic Alzheimer’s disease. The drug, manufactured by Eli Lilly, is also recommended for adults with mild cognitive impairment (MCI) and mild dementia stages of the disease.
In its pivotal Phase 3 study, the treatment demonstrated a remarkable ability to slow cognitive and functional decline by up to 35% compared to a placebo over 18 months. Additionally, it reduced the participants’ risk of advancing to the next clinical stage of the disease by up to 39%. This approval marks a significant milestone in the ongoing battle against this debilitating condition, which impacts memory, thinking, and behavior, ultimately robbing people of their independence and quality of life.
Understanding Alzheimer’s
Before beginning to understand how this drug will impact those with Alzheimer’s, it’s important to first understand how the disease works. Alzheimer’s disease is a progressive brain disorder that impacts over 6.5 million Americans, categorically more women. It steadily diminishes memory and cognitive functions, eventually hindering the ability to perform even the simplest tasks.
Although the precise causes of Alzheimer’s are still not fully understood, the disease is defined by specific brain changes, such as amyloid beta plaques. (Amyloid naturally accumulates in the brain as people age, building up and damaging nerve cells over time, causing them to die. Elevated levels of amyloid are associated with an increased risk of developing dementia.) These alterations result in the loss of neurons and their connections, profoundly affecting a person’s memory, thinking, and communication abilities.
“Alzheimer’s disease exists on a spectrum: Preclinical Alzheimer’s is a multi-decade period at the start of the spectrum in which pathological changes are taking place in the brain, prior to the onset of any cognitive symptoms,” Alicia Barber, PhD, founder of Brain Health Media, tells Flow Space. “Therefore, asymptomatic individuals presenting with amyloid positivity (quantified with PET brain imaging) could be in the preclinical Alzheimer’s phase, and are more likely to go on to develop dementia due to Alzheimer’s disease in the future.”
Barber emphasizes that while a positive amyloid PET scan can indicate Alzheimer’s disease, it is not definitive. Additionally, the presence of amyloid plaques does not always align with cognitive impairment. Kisunla was proven to help the body remove the excessive amyloid plaques that build up in the brain. By doing this, the drug can slow down the decline in abilities such as remembering new information, important dates, planning and organizing, cooking and using household appliances, managing finances, and safely being alone.
How effective is Kisunla compared to other medications?
Kisunla was tested in a study with 1,736 people who had early symptoms of the disease. Participants were randomly given either Kisunla or a placebo without knowing which one they received. The study lasted up to 72 weeks, with Kisunla given every four weeks. Results showed that people taking Kisunla had better memory, thinking skills, and ability to do daily tasks compared to those taking the placebo. It also slowed progression of Alzheimer’s to the next, more-advanced stage by 39%.
“These were clinical trial choices that, in general, the researchers were at a position where they believed that treating patients earlier is better,” Dr. Jeffrey Cummings, MD, a Research Professor in the Department of Brain Health at the University of Nevada tells Flow Space. “Because when the disease is less established, you’re trying to keep patients at that level. The idea is to prevent the emergence of any kind of forgetfulness or cognitive symptoms.”
The average age of participants in the study was 73, and the group included mostly white individuals, with some Asian, Hispanic, Latino, Black, and African American participants. When looking at the results for both men and women taking Kisunla, the drug is effective in all people.
Other Alzheimer’s drug options include Lecanemab (Leqembi), another injectable approved in January 2023, which has been shown to slow cognitive decline by 27% compared to a placebo over 18 months. Another similar drug, aducanumab (Aduhelm), was the first amyloid-targeting medication approved in 2021, but its manufacturer, Biogen, has decided to remove it from the market by November 2024 due to its accelerated approval.
“The amyloid that accumulates in the brain forms plaques, and these drugs all work to remove those plaques,” Dr. Cummings says. “So at that level, they’re all the same. At the level of how they do it exactly, and how the drugs are administered, and the side effects, there are differences among all of them. But their basic mode of action is very similar.”
Are there any side effects?
Kisunla can sometimes cause a side effect called amyloid-related imaging abnormalities (ARIA). This side effect happens with drugs that target amyloid plaques in the brain. Most of the time, ARIA doesn’t cause any symptoms and can be found with MRI scans. When ARIA does happen, it might show up as temporary swelling in the brain that usually goes away on its own, or as tiny spots of bleeding in or on the brain. Rarely, there can be larger areas of bleeding, which can be very serious and even life-threatening.
“It turns out that as you pull this amyloid protein out of the brain, you will also pull the same protein out of the blood vessel, and that temporarily weakens the vessel wall,” Dr. Cummings says. “So there can be an escape of fluid and blood from the blood vessel that goes into the brain, and that’s what causes the swelling and the micro hemorrhages. It was 24% of the patients who had this phenomenon, and for only 6% of the patients it actually caused symptoms.”
Dr. Cummings explained that many people experienced this event, but it was only discovered because researchers knew to monitor for it using MRI scans. He goes on to say that when this happens users are required to stop the drug until that change goes away on the MRI. After that, patients can resume taking the drug.
Kisunla can also cause allergic reactions, some of which can be serious and happen during or right after the treatment (though patients taking infusions of the drug once a month will be carefully monitored in a clinical setting for any signs of adverse effects). Another common side effect is headaches, which Dr. Cummings says it is the most common symptom. Despite this downside, Dr. Cummings remains optimistic and believes it is a significant step forward in treating Alzheimer’s.
“I think it’s tremendous for patients to have alternatives,” he says. “When there’s just one approved drug that means you have one choice. So it’s great that patients have choices and it’s great that we’re reproducibly showing this relationship between the lowering of the protein and the slowing of the progress of the disease.”