Existing Treatments and Drugs for Alzheimer’s Disease

While treatments for the symptoms of Alzheimer’s disease have existed for some time, efforts to develop drugs to modify or slow the progression of Alzheimer’s disease largely have been unsuccessful—until recently. In 2021, the landscape changed when the U.S. Food and Drug Administration (FDA) approved a new anti-amyloid treatment. Since then, advancements in drug discovery have led to the approval of two new Alzheimer’s medications by the FDA.

The Amyloid Cascade Hypothesis postulates that preventing or reversing the aggregation and accumulation of amyloid beta in the brain, if done sufficiently early in the disease process, may prevent a series of downstream consequences, including neuroinflammation, neurodegeneration and cognitive decline. Each of these drugs belongs to the class of monoclonal antibodies directed against the buildup of amyloid beta in patients at the early stage of the disease. This class of drugs binds to the amyloid plaques in the brain and triggers their degradation and resulting removal by the brain’s immune system.

DISEASE-MODIFYING DRUGS

KISUNLA™
On July 2, 2024, the FDA approved Kisunla™ for the treatment of early symptomatic Alzheimer’s disease. Clinical trials have shown that treatment can slow memory decline but does not stop disease progression, and is not a cure. The treatment is delivered in a clinical setting once a month intravenously, and physicians can consider halting the treatment when a PET scan indicates that the amyloid level in the brain of the patient is sufficiently cleared. The cost of the drug, excluding provider or administrative costs, is $32,000 a year. Some 69% of patients were able to end treatment by 18 months.

The FDA label recommends genetic testing to determine whether the patient has APOE4 due to the higher risk of serious side effects in individuals who carry two copies of the gene. Read more here.

LEQEMBI®
On July 6, 2023, the FDA granted full approval for Leqembi, another anti-amyloid treatment for Alzheimer’s disease developed by pharmaceutical companies Eisai and Biogen. As a monoclonal antibody, Leqembi is designed to reduce the amount of amyloid beta in the brain. The approval is for the treatment of mild cognitive impairment and mild dementia due to Alzheimer’s disease; clinical research that could result in wider use is ongoing. Medicare covers the costs of the drug for patients who meet the eligibility criteria. To learn more about Leqembi, please visit this page.

ADUHELM®
In 2021, the FDA approved the first anti-amyloid treatment, Aduhelm. The approval of Aduhelm marked the first new drug for Alzheimer’s disease to reach the market in 18 years, and the first intended to change the course of the disease, not just treat symptoms. The drug was approved using an accelerated approval pathway and, during its decision-making process, the FDA tasked a standing external advisory group of experts to discuss and assess data presented by Biogen and FDA officials. Some members of this group, scientists and clinicians, had significant experience with Alzheimer’s disease, while others specialized in other neurological areas and scientific disciplines. All of the members of the advisory group voted that the data provided insufficient evidence of clinical efficacy to justify approval of Aduhelm. Subsequently, Medicare declined to cover the expense of the drug and, in January 2024, Biogen discontinued Aduhelm. Learn more here.

TREATMENTS FOR SYMPTOMS OF ALZHEIMER’S DISEASE

There are several drugs approved for symptomatic relief of Alzheimer’s disease, but these do not alter the underlying pathology of the disease. They may not work for every patient and may only work for a limited amount of time. While these drugs will not stop or slow disease progression, they may offer help with the management of cognitive and behavioral symptoms.

RAZADYNE®, ARICEPT® AND EXELON®
Cholinesterases are a family of enzymes present in the central nervous system. This family of enzymes breaks down acetylcholine, a natural chemical that helps nerve cells to communicate. Reduced levels of acetylcholine may contribute to some of the symptoms of Alzheimer’s disease. Cholinesterase inhibitors prevent the breakdown of acetylcholine, facilitating the needed communication and signals between nerve cells. Commonly prescribed cholinesterase inhibitors are galantamine (Razadyne), donepezil (Aricept) and rivastigmine (Exelon).

NAMENDA®
NMDA (N-methyl-D-aspartate) receptor antagonists are a class of drugs that decrease abnormal deactivation of the neurons in the brain due to excess levels of the chemical messenger glutamate. Excessive activation of the NMDA receptor by glutamate causes neuronal hyperactivity, impairing proper function and even causing death of neurons. Blocking the NMDA receptor keeps neurons functioning and protects them from cell death. The most common NMDA receptor antagonist is memantine, under the brand name Namenda or in generic form. The medication is prescribed for patients with moderate to severe Alzheimer’s disease, is taken orally and works by blocking the glutamate binding of the NMDA receptor.

REXULTI®
One common and distressing symptom of Alzheimer’s disease is psychosis, including agitation. In 2023, the U.S. Food and Drug Administration announced supplemental approval of the oral tablet Rexulti for the treatment of agitation associated with dementia due to Alzheimer’s disease.

BELSOMRA®
Another common symptom of Alzheimer’s disease is difficulty sleeping. Sleep disturbances worsen as the disease progresses, and may affect up to 25% of people with mild to moderate dementia, and up to 50% of people with severe dementia. The hormone orexin is a wake transmitter that plays a role in the sleep–wake cycle. The prescription medication Belsomra is taken orally and helps regulate sleep by blocking orexin.

The advancement in disease-modifying treatments is a great step forward in the development of medications to treat Alzheimer’s disease, and researchers continue their work to gain a deeper understanding of the disease, leading to the development of more effective treatments.