Experimental Alzheimer’s drug donanemab outperforms Leqembi in clinical trial: Shots

A large study of an experimental Alzheimer’s disease drug by pharmaceutical company Eli Lilly & Co. appears to slow the worsening of the degenerative brain disease.

Darron Cummings/AP

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Darron Cummings/AP

A large study of an experimental Alzheimer’s disease drug by pharmaceutical company Eli Lilly & Co. appears to slow the worsening of the degenerative brain disease.

Darron Cummings/AP

Patients in the early stages of Alzheimer’s disease may soon have a new option to avoid memory and thinking loss.

In a study of more than 1,700 people, the experimental drug donanemab slowed the progression of Alzheimer’s disease by around 35%, scientists say reported at the Alzheimer’s Association International Conference in Amsterdam.

The result, published simultaneously in the newspaper jama, suggests donanemab is at least as effective as the newly approved drug This group (lecanemab), which has been found to reduce progression by approximately 27%.

“This is the largest effect ever seen in an Alzheimer’s disease trial for a disease-modifying drug,” says dr. Daniel Skrovonskydirector of research and development at Eli Lilly, which manufactures donanemab.

The company has submitted the results to the Food and Drug Administration and expects a decision by the end of the year.

But experts warn that donanemab is not a cure, and its benefits only amount to a delay of about seven months in memory and thinking loss.

“I think it will make a difference for people,” says Dr. Reisa Sperling, who directs the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital in Boston. “But we have to do better.”

Early treatment is key

Donanemab, like Leqembi, is a monoclonal antibody designed to remove a substance called beta-amyloid from the brain. Beta-amyloid tends to form sticky plaques in the brains of people with Alzheimer’s disease.

The donanemab study focused on people whose brain scans showed plaques and other changes associated with the onset of Alzheimer’s disease. They had only mild cognitive symptoms.

Even within this group, however, people with more advanced disease saw less benefit from the drug.

“What we’ve seen is that the ability to slow disease progression is strongest if you catch this disease earlier,” Skrovonsky said.

The study also suggests that patients may not need monthly intravenous infusions of donanemab for life.

Patients were taken off the drug once the plaques in their brains had mostly cleared, usually within a year. The plaques did not reappear during the 18-month study, and the benefit to memory and thinking continued.

This appears to give donanemab an advantage over Leqembi, which requires ongoing treatment. But it’s still unclear whether the benefits of donanemab will persist for years after treatment ends.

“I imagine in the future we will have this initiation phase where we will remove the plaque and then we will have maintenance treatment,” says Sperling.

Donanemab and Leqembi can cause dangerous swelling or bleeding in the brain.

In the donanemab study, brain scans revealed this side effect in about 25% of patients. About 6% had symptoms, such as headaches, nausea and confusion. Three patients died.

A new era for the treatment of Alzheimer’s disease?

The results with donanemab and Leqembi provide strong evidence that clearing amyloid from the brain can slow Alzheimer’s disease. This approach, known as the amyloid hypothesis, had been questioned after dozens of other amyloid drugs failed to help patients.

One reason for the recent success is earlier treatment, Sperling says. Instead of treating patients who have already suffered significant brain damage from Alzheimer’s disease, the researchers focused on people whose brains are still relatively healthy.

Another factor is how researchers approach treatment, Sperling says.

“We’ve learned to be more aggressive with the dosage,” she says, which rapidly reduces amyloid to very low levels in the brain.

But scientists still don’t know which forms of amyloid offer the best target.

Single amyloid molecules appear to be harmless. But scientists have learned that when these molecules start to clump together, they can take on toxic forms. Eventually, these clumps end up in plaques between brain cells.

“There has been a debate in our field for 30 years now about whether the plaques themselves are the source of the problem,” says Sperling. And the results with donanemab and leqembi are unlikely to end that debate.

Donanemab is designed to specifically target plaques. Leqembi is designed to target other forms of amyloid, although it also clears plaques.

Yet both drugs appear to slow memory and thinking loss in patients with early-stage Alzheimer’s disease.

A study Sperling is involved in could help answer the amyloid issue by treating people who still have very little plaque in their brains.

“If we’re seeing benefits even at this point,” Sperling says, “one could argue that it’s not just the plaque” that erodes memory and thought.