What treatments are in the pipeline for Alzheimer disease?

By Samar Mahmoud, PhD | Medically reviewed by Kristen Fuller, MD
Published September 27, 2022

Key Takeaways

  • The prevalence of Alzheimer disease is increasing as the worldwide aged population increases.

  • Novel therapeutics have been introduced in recent years to treat Alzheimer disease.

  • Treatments for Alzheimer disease currently being investigated include anti-amyloid monoclonal antibodies, beta- and gamma-secretase inhibitors, and tau aggregation inhibitors.

With the size of the global aged population increasing, the incidence of Alzheimer disease (AD), the most common type of dementia, is also on the rise.

Positive strides have been made in recent years. Two FDA-approved medications (donepezil and rivastigmine) may slightly slow down progression of symptoms in individuals with mild AD; however, their long-term effects on behavior, thinking, and independent living are unknown.[]

AD costs and prevalence

The Alzheimer’s Association reports that in the US alone, there are an estimated 6.5 million individuals with AD; this number is projected to increase to 12.7 million by the year 2050. According to Alzheimer’s Disease International, the global prevalence of AD is expected to more than triple from 50 million as of 2020 to approximately 152 million by 2050.

Novel therapeutics are needed, to not only prevent the onset of AD but also slow its progression and improve symptoms.

A tremendous cost burden is associated with AD; the cost of caring for patients with AD and related dementias was $355 billion in 2021. Also the emotional and mental toll on caretakers, specifically family member caretakers who care for their loved ones with AD, is significant.

Aducanumab approved

In 2021, the FDA approved aducanumab (Aduhelm) for the treatment of mild symptoms of AD patients, such as individuals who are still independent in basic daily functioning. It was (controversially) approved using the accelerated approval pathway, and was the first novel therapeutic to be approved for AD since 2003.[]

Aducanumab is the first AD treatment that targets the amyloid beta plaques that form in the brains of AD patients and are a hallmark of the disease. It is a monoclonal IG1 antibody that binds to the amyloid beta protein at amino acids 3–7. Research showed that aducanumab led to a decrease in these plaques in patients with AD.

Plaque reduction, however, has not been a reliable marker for cognitive function in past trials.

Not everyone with plaques has or will get AD, and other plaque-reducing medications have not shown meaningful patient benefit. Aducanumab was approved on the basis that Biogen conducts further, post-approval clinical studies to ensure that the drug provides clinical benefit.

In addition to aducanumab, there are two additional monoclonal antibodies, lecanemab and donanemab, that have shown promising results in clinical trials. Another monoclonal antibody, solanezumab, didn’t offer patients with mild or moderate AD any benefit and as a result, these phase 3 trials were terminated.

A phase 2/3 clinical trial is testing solanezumab in individuals who have a genetic mutation that may put them at risk for developing AD. Solanezumab and gantenerumab (an additional AD investigational therapy) will both be tested against placebo to see if they can reduce patients’ rate of decline.[]

Exploring additional mechanisms of action

AD research has shown that beta-amyloids are synthesized in a two-step process that’s carried out by different enzymes.[] Beta- and gamma-secretase inhibitors aim to inhibit the activity of these enzymes. Enthusiasm has decreased for beta-secretase inhibitors, however, as these drugs didn’t slow down AD progression and were associated with significant side effects.

Tau tangles are another molecular hallmark of AD.

Researchers are looking into different ways to stop the tau protein from forming these microscopic fibers. Tau vaccines and aggregation inhibitors are currently being investigated in clinical trials.

What’s in the pipeline?

According to a 2022 review article published in Alzheimer’s and Dementia: Translational Research and Clinical Interventions, there were 143 therapeutic agents in the developmental pipeline for AD as of January 25, 2022.[] More specifically, there were 31 treatments for AD in 47 phase 3 trials, with most of the investigated agents being disease-modifying therapies.

What this means for you

The rise of AD constitutes a public health crisis. Novel therapeutics are needed. Promising agents such as aducanumab have been FDA-approved for AD treatment. Other therapeutics are currently in the developmental pipeline and may show promise in improving quality of life for AD patients. Physicians should stay current on such emerging treatments and clinical trials, as they could impact quality of care for your aging patients. It may also be worthwhile to see if your patients qualify for enrollment in one of the many clinical trials being conducted.

Read Next: ALZ-801 trial results announced: A breakthrough in Alzheimer's treatment?
Share with emailShare to FacebookShare to LinkedInShare to Twitter