Eli Lilly's experimental Alzheimer's disease drug slowed the rate at which participants lost their ability to think and care for themselves, according to a small clinical trial—but experts say there's reason to view the results with caution.

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About Alzheimer's disease

Alzheimer's disease is a type of dementia traditionally defined as a clinical syndrome involving the progressive decline of cognitive abilities—particularly memory loss—that ultimately results in the loss of independence. About 5.8 million Americans have Alzheimer's disease, and CDC projects that number will reach 13.9 million by 2060 as baby boomers age. There is no proven treatment for the disease, though there are medications that temporarily alleviate the disease's symptoms.

So far, research into potential treatments for Alzheimer's disease have mostly focused on the beta amyloid protein, which accumulates in the brains of patients with Alzheimer's years before they experience memory loss. Researchers have hypothesized that the beta-amyloid buildup in the brain is responsible for the cognitive decline seen in Alzheimer's patients.

Largely, researchers have agreed that Alzheimer's disease always progresses the same way, with amyloid accumulating in a patient's brain, then a protein called tau appearing, and a patient's neurons dying. That widely held belief suggests attacking amyloids is key to preventing the disease.

Lilly's experimental drug slows cognitive decline, early data shows

Lilly said its experimental drug, called donanemab, is a monoclonal antibody designed to target "a modified form of beta amyloid called N3pG." The company tested the drug candidate's effectiveness in a Phase 2 clinical trial.

For the two-year trial, Lilly recruited participants based on brain scans rather than symptoms. Each participant had brain scans showing significant accumulations of amyloid and the presence of tau, which forms spaghetti-like tangles in the brains. "We needed mild to moderate tangle pathology, but not so many tangles that perhaps the disease is beyond hope," Daniel Skovronsky, the company's chief scientific officer, said.

Overall, researchers enrolled in the trial 272 participants with brain scans showing both the buildup of amyloid and mild to moderate tangles from tau. According to STAT+, the participants had an average baseline of 108 centiloids—which is a measurement unit used to gauge amyloid plaque in brain scans—at the beginning of the trial.

During the trial, the researchers gave the participants either a placebo or donanemab by IV infusion every four weeks. The researchers then used a questionnaire to measure each participant's cognition and ability to perform daily functions, such as dressing. The patients' caregivers often filled out the questionnaires.

The researchers also conducted brain scans on each participant every six months. If the researchers found the participant's amyloid plaques had dropped to "below 25 centiloids for any two consecutive measures or 11 centiloids at any one measure," they would stop giving the patient Lilly's experimental treatment and instead administer a placebo.

In a release issued Monday, Lilly said its researchers found donanemab slowed the decline in memory and ability to perform daily activities by 32% after 18 months among participants who received the experimental therapy when compared with those who received a placebo. In addition, Lilly said the researchers found an average decrease of 84 centiloids from the 108 centiloids baseline among patients who received donanemab after 76 weeks. According Lilly, a measure of "less than 25 centiloids is typical of a negative amyloid scan."

What the results may mean for Alzheimer's care

Many stakeholders and observers welcomed the company's findings.

"This is what we've been waiting for, a clean, positive study based on a compelling hypothesis with a drug that adequately covers the target," Skovronsky said.

Michael Weiner, a leading Alzheimer's researcher at the University of California-San Francisco, said the study's results will need to be replicated, but the findings are "big news."

"This holds out hope for patients and their families," Weiner added.

Lon Schneider—a professor of psychiatry, neurology, and gerontology at the University of Southern California—said if the findings are accurate, this would mark the first time a drugmaker has produced positive results in a Phase 2 clinical trial for an Alzheimer's drug. According to the New York Times, other Alzheimer's drugs were either never tested in a Phase 2 trial or they failed to generate positive results in a Phase 2 trials.

Some experts caution that it's too early to celebrate the findings

However, experts said observers should view the company's findings with caution because, in the past, preliminary data has been promising for many Alzheimer's treatments that ultimately failed to treat the disease.

Schneider also said it's too early to know whether the company's findings are accurate, because Lilly did not release the data needed for experts to conduct a thorough analysis of the results, such as the number of declines in function among the participants rather than the percentages.

In addition, some experts noted that observers should view the results with a degree of skepticism because of the trial's size.

Ronald Petersen, who directs the Mayo Clinic Alzheimer's Disease Research Center, said, "These data are fine to rationalize doing the larger study, but these data are too preliminary to conclude any clinical benefit or efficacy."

For its part, Skovronsky said Eli Lilly will release additional data from the trial during an upcoming medical meeting and in an article that's been submitted for publication in a peer-reviewed medical journal. Skovronsky added that Lilly also plans to discuss the trial's results with FDA and regulators in other countries to determine whether the company can help patients access the drug.

According to STAT+, the company's conversations with regulators suggest Lilly may be hoping to receive an approval for the experimental treatment based on its preliminary data, although the company has begun enrolling participants in a second trial. Typically, regulators require data from large, well-conducted clinical trials before approving an experimental treatment (Kolata, New York Times, 1/11; Rockoff, Wall Street Journal, 1/11; Herper, STAT+, 1/11 [subscription required]; Eli Lilly release, 1/11).