New Alzheimer’s Drugs Show Promise for Patients in Early Stages

• Two new drugs from Eli Lilly—Leqembi and donanemab—are showing promising results of slowing Alzheimer’s when the disease is in the early stages.
• Leqembi was approved by the FDA in January; donanemab is currently being considered for FDA approval.
• Currently, Leqembi is available to individuals living with mild cognitive impairment, in the early stages of Alzheimer’s disease.

Two new Alzheimer’s drugs are showing promising results of slowing the disease in the early stages.

A new study reported that a new Eli Lilly drug, donanemab, slowed the progression of Alzheimer’s by about 35%.

For people at the earlier stage of the disease, donanemab appeared to slow the decline in memory and cognitive function by roughly 4.5 to 7.5 months over an 18-month period compared with those taking a placebo.

The slowing was also the greatest for early-stage patients when they had less of tau, a protein that creates “tangles” in the brain.

The data, presented earlier this month at the Alzheimer’s Association International Conference in Amsterdam, suggests that donanemab is at least as effective as another Eli Lilly drug, Leqembi, which was found to reduce progression of Alzheimer’s by about 27%.

Leqembi was approved by the Food and Drug Administration in January. Accessibility of the drug is already being discussed.

The Centers for Medicare and Medicaid Services announced it would “provide broader coverage” of Leqembi, meaning it will be covered for most Medicare patients who show early signs of cognitive problems and elevated levels of amyloid.

Meanwhile, donanemab is currently being considered for FDA approval.

“These drugs are not a cure for Alzheimer’s,” Christopher Scuderi, DO, FAAFP, Medical Director for Value-Based Care at Northeast Florida Millennium Physician Group, told Health. “They help slow down progression for patients with early disease which is a large positive step and can help patients live independently longer.”

Comparing Leqembi and Donanemab

Both Leqembi and donanemab, which are infusions administered intravenously, are the first drugs with clear evidence of slowing cognitive decline in patients with Alzheimer’s.

They work by targeting amyloid, a protein found in the human brain. An accumulation of amyloid can cause the proteins to stick together and form clumps that can become plaques that can cause Alzheimer’s disease.

Both Leqembi and donanemab have not been compared directly to one another in research studies, and because each drug’s individual trials differ in patients, design, and process, it’s difficult to compare the two to determine which one might be more effective.

But they do have serious side effects.

Two main concerns the study found were swelling and bleeding in the brain. The donanemab trial had higher rates of swelling and bleeding than the Leqembi trial, and neither drug reverses or repairs brain damage already caused by Alzheimer’s.

Another concern is the lack of representation in the clinical trials of these drugs.

Nicole Purcell, DO, MS, a general neurologist and Alzheimer’s Association senior director of clinical practice told Health that the Alzheimer’s Association remains disappointed that so little progress has been made in improving the representation of all affected communities in Alzheimer’s clinical trials.

“For example, dementia disproportionately affects Black and Hispanic Americans yet, too often, they are severely underrepresented in treatment studies,” she said. “It is critical that clinical trials accurately reflect the population they seek to serve."

The donanemab study also reported that three deaths were linked to the drug in its clinical trial; three participants in the Leqembi trials also died after experiencing brain swelling and bleeding.

While these drugs can have severe side effects, experts are hopeful about the positive impact they could have on patients with Alzheimer’s.

“By slowing the progression of the disease when taken in the early stages of Alzheimer’s, drugs in this class may enable individuals to have more time to participate in daily life and live independently,” Purcell said.

Rolling Out Accessibility of the New Drugs

With the approval of the new drugs comes some important reminders about specific populations they’re approved for.

The FDA granted traditional approval to Leqembi for the treatment of patients with mild cognitive impairment (MCI). The Phase 3 Leqembi clinical trials, as well as the trials of donanemab, studied people in this condition.

The therapies have not yet been tested in people with more advanced Alzheimer’s disease.

According to Purcell, this emphasizes the importance of accurate, early diagnosis of Alzheimer’s to understand if individuals are eligible for these treatments.

“At the same time, there is an urgent need for safe and effective treatments for people in all stages of Alzheimer’s disease and all other dementia, and for proven effective risk reduction strategies,” she said.

A small study, published earlier this month, confirmed due to the specific criteria required of each patient in the clinical trials, only a small percentage of people with early-stage Alzheimer’s disease are eligible for these drugs.

Researchers found that 47% of the participants met the inclusion criteria for the lecanemab (sold under the brand name Leqembi) trial, but after applying the exclusion criteria, just 8% would have been eligible for the drug.

The criteria excluded individuals with health issues like cardiovascular disease, stroke, a history of cancer, and brain injuries.

For aducanumab (sold under the brand name Aduhelm), the first approved treatment for Alzheimer's in over 20 years, just 5%, or 12 of the people studied, would have been eligible for the trial after accounting for inclusion and exclusion criteria.

The criteria excluded individuals with health issues like uncontrolled high blood pressure.

What Is Aduhelm?

Aduhelm was granted conditional approval by the FDA in 2021. Like Leqembi and donanemab, it works to remove amyloid from the brain and slow the progression of Alzheimer’s. Like the other two drugs, it’s administered as an infusion.

Aduhelm is typically prescribed in the early stages of Alzheimer’s, whereas Leqembi and donanemab might be prescribed as the disease progresses.

As FDA approval of the drugs is based on the findings of the clinical trials, only a small number of people with Alzheimer’s are likely to be eligible to use the drugs right away. For patients unsure if they qualify for these types of drugs, it’s best to consult with your physician.

Because of the limited number of people who qualify for these drugs, experts agree that more research is to be done to help better understand how to reach more patients at all stages of Alzheimer’s and those who do not meet the specific criteria.

However, the approval of these drugs provides doctors with options to offer patients who have early symptoms, Scuderi said.

“Having a class of medication that can alter the course of Alzheimer’s disease early on will encourage family physicians to be vigilant in looking for signs of mild cognitive impairment to help identify patients who can possibly benefit from these treatments,” Scuderi said.

Purcell added that as early diagnosis and treatment hopefully become more common, there will be changes for medical professionals to also offer assistance with living with Alzheimer’s, like lifestyle changes, caregiving, and guidance with future planning.

As more patients are able to access these life-changing treatments, medical professionals expect these drugs to make a positive and rewarding impact on those suffering from Alzheimer’s

“What these drugs offer is hope,” Scuderi said. “As we start to see early success in treatment this opens the door to further research that will hopefully lead to more impactful treatment in the future.”