New Alzheimer's Disease Drugs Receive FDA Approval, Offering Hope

August 15, 2023
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Previously, doctors have only been able to manage the symptoms and effects of Alzheimer’s disease but have been unable to treat the disease itself. Medications and coping skills have helped patients and families manage sleeplessness, anxiety, and other Alzheimer’s symptoms, but no medication until now has slowed disease progression. This year three drugs have been submitted for review or approved by the U.S. Food and Drug Administration (FDA) to help Alzheimer’s patients—two of which are reported to slow the course of the disease (lecanemab and donanemab), and one that manages agitation in Alzheimer’s patients (brexpiprazole).

Alzheimer’s disease is an irreversible and progressive brain disease that slowly destroys memory and cognitive and motor function. At the end stage of the disease, most patients require constant care and may be bed-bound. While the cause of Alzheimer’s disease is not known, patients diagnosed have changes in the brain, including amyloid-beta plaques and neurofibrillary tau (also called tangles)—clusters of abnormal proteins which disconnect important neurons that power key brain functions. As the most common form of dementia, over 6 million Americans are currently living with Alzheimer’s disease, with that number doubling every five years. However, for the first time, there is new hope when it comes to treatment, with the 2023 developments regarding the drugs lecanemab, donanemab, and brexpiprazole.

These novel drugs are providing new options for those with early Alzheimer’s disease, with the possibility of more time with a better quality of life.

Treatment Options Target Sticky Plaque

Lecanemab

Lecanemab (Leqembi) is second in a new category of drugs approved by the FDA to treat Alzheimer’s disease. This new drug category targets the disease at the amyloid-beta plaques that build up in the brain. These sticky plaques disrupt brain activity and are thought to influence the progression of Alzheimer’s.

Approved originally in early 2023 under the FDA’s Accelerated Approval pathway based on the urgent, unmet need for treatment, lecanemab was shown to reduce amyloid-beta plaque, a known marker of Alzheimer’s that hinders cell function and cannot be broken down or released. It has now been granted full, traditional FDA approval.

Lecanemab is administered through an IV infusion every two weeks and is intended for patients with mild dementia or mild cognitive impairment and was not studied in patients with further disease progression.

Donanemab

Donanemab is a monthly infusion, which, like lecanemab, targets and clears amyloid-beta plaques from the brain for early-stage Alzheimer’s patients. Its maker, Eli Lilly, reports that donanemab slows the progression of Alzheimer’s disease by about one-third. Another promising outcome reported was that patients were able to go about more of their typical lives and activities, including driving, participating in hobbies, and discussing current events.

Eli Lilly recently filed for full FDA approval for donanemab and expects a decision by the end of 2023.

Understanding The Risks and Benefits

While lecanemab and donanemab represent hopeful progress in the fight against Alzheimer’s disease, like most other drugs, there are risks and limitations to what they can accomplish. For starters, these drugs provide about 6-7 months of benefits after 18 months of treatment and may slow the progression of Alzheimer’s disease but will not stop it.

Additionally, not all patients with Alzheimer’s disease will be a good candidate for either lecanemab or donanemab.

Good candidates for lecanemab or donanemab include patients:

  • with very early evidence of memory loss or who are early in their Alzheimer’s disease diagnosis
  • who have the presence of amyloid-beta plaques in their brain
  • who demonstrate a low risk for severe side effects, based on genetic testing
  • who are able to commit to the logistics of treatment, which include periodic half-day infusions over an 18-month period and 7-11 MRI scans in that time, as well as transportation and support
  • who do not meet exclusionary criteria, such a severe depression or the need to take blood thinners

Once a patient is cleared to take lecanemab or donanemab, some experience side effects, some of which are severe enough to stop treatment briefly or completely. One risk of both drugs is that they can cause blood vessels in the brain to leak, which produces swelling known as amyloid-related imaging abnormalities-edema or ARIA-E. Another risk factor is that some of the amyloid plaques can live in the walls of blood vessels and when removed by the drugs, cause a small stroke, or ARIA-H (hemorrhage).

“For people who are going to be able to take this medication, I think that this does represent an improvement over what we are able to offer them right now,” says Dr. Stephen Bonasera, Chief, Division of Geriatrics Palliative Care & Post Acute Care. “This is a real advancement, and some patients will have a lot of benefit from this. However, taking these drugs is an individualized decision that patients and their families need to think about, because they do come with significant risks.”

The best course of action is to discuss the risks and benefits of any treatment plan with the patient’s doctor to determine what will be best for them.

Brexpiprazole: A Way to Lessen Agitation

Brexpiprazole (Rexulti) is a drug that treats the agitation associated with Alzheimer’s disease dementia (AAD). The first of its kind to be approved by the FDA, brexpiprazole is shown to improve symptoms of agitation in patients with AAD.

Agitation has been reported in 76% of patients with Alzheimer's, and as the aging population grows, those instances are likely to rise. Symptoms of agitation can range from restlessness and pacing to verbal and physical aggression, which can be dangerous to the patient themselves and those around them.

Brexpiprazole is administered in pill form, and the dosage is gradually increased over time. While the exact way it works isn’t clear, it is thought to regulate neurotransmitters for dopamine and serotonin, chemicals in our brain that regulate bodily functions like sleep, emotion, and others.

It is important to note that brexpiprazole has a black box warning from the FDA indicating a risk of death in older adults with psychosis related to dementia.

Traditionally used for major depressive disorder (MDD), brexpiprazole represents a variety of drugs that may be intended for one purpose but will also work for other diseases and disorders. Because it has been clinically studied and proven to be safe and effective for the treatment of AAD, brexpiprazole offers families an additional, viable medical option to consider if agitation from Alzheimer’s is causing distress or even injury.

Risk Management and Early Detection of Alzheimer’s

While the most significant risk factor for Alzheimer’s disease is age, you can modify some of your risk through exercise and a healthy diet, reducing high blood pressure, and keeping yourself physically and mentally engaged.

Alzheimer’s disease is difficult for both the patient and their family, but there is renewed hope, thanks to new treatment options. With continued research, there is the possibility for new drugs and treatment plans, and better outcomes for the patient and their family. These outcomes can include better motor and cognitive function, more time to spend with family, the ability to participate in activities, and better overall quality of life.

Talk with your doctor as soon as possible if you or a loved one is experiencing early symptoms of Alzheimer’s disease, such as difficulty with memory or cognitive function. The earlier Alzheimer’s disease is detected and diagnosed, the better treatment options will work to change the course of the disease and maintain quality of life.

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