WASHINGTON – An Eli Lilly drug to combat Alzheimer’s disease won the backing of federal health advisers Monday, setting the stage for the long-awaited approval of the treatment for people with mild dementia caused by the brain disease.
Advisors to the Food and Drug Administration (FDA) voted unanimously that the drug’s ability to slow the disease outweighs its risks, including side effects such as brain swelling and bleeding, which will have to be controlled .
“I think the evidence from the trial is very strong and demonstrates the effectiveness of the drug,” said Dean Follmann, a statistician at the National Institutes of Health.
The FDA will make a final decision on its approval later this year. If the agency accepts the expert group’s recommendation, donanemab would be the second Alzheimer’s drug authorized in the US that has been convincingly shown to slow cognitive decline and memory problems due to this disease. The FDA last year approved a similar infusion drug, Leqembi, from Japanese drugmaker Eisai.
The slowdown seen with both drugs is several months, and experts disagree about whether patients or their loved ones will be able to detect the difference.
But the approach Lilly took to studying its monthly treatment raised questions among FDA reviewers.
Patients in the company’s study were grouped based on their levels of a brain protein, called tau, that predicts the severity of cognitive problems. This led the FDA to question whether patients should be given a brain scan to detect the presence of tau before being given the drug. However, most panelists felt there was enough evidence of the drug’s benefits to prescribe it widely, without needing to test the protein.
“Imposing a requirement for tau imaging is unnecessary and would raise serious practical and treatment access problems,” said Dr. Thomas Montine of Stanford University, who chaired the panel and summarized his opinion.
Overall, Lilly’s results mirrored Leqembi’s, with both drugs showing a modest slowing of cognitive problems in early-stage Alzheimer’s patients. The Indianapolis-based company conducted a study of 1,700 patients in which it was shown that patients who received monthly intravenous infusions of its drug declined 35% more slowly than those who received a sham treatment.
The FDA was expected to approve the drug in March. But instead, the agency said it would ask its panel of neurology experts to publicly review the company’s data, an unexpected delay that surprised analysts and investors.
The meeting was prompted by several unusual approaches to the way Lilly tested its drug.
One of the changes consisted of measuring the patients’ tau protein and excluding those with very low or non-existent levels. However, the panelists said there was enough data on other measures to be confident that almost all patients could benefit from the drug, regardless of their levels.
In another key difference, Lilly studied taking the drug off patients when they reached very low levels of amyloid, a sticky brain plaque that contributes to Alzheimer’s disease.
Lilly scientists suggested that treatment interruption is a key advantage of their drug, which could reduce side effects and costs. However, FDA staff noted that Lilly provided little data on the optimal time to stop treatment or how quickly patients might need to restart it.
Despite these doubts, many panelists considered the possibility of stopping doses promising.
“This is a huge cost savings for society, since we’re talking about expensive treatment and monitoring,” said Dr. Tanya Simuni of Northwestern University. She and other experts said patients would need to be followed up and tested to see how they are doing and whether they need to resume treatment.
The main safety concern with donanemab was brain inflammation and bleeding, a problem common to all amyloid-targeted drugs. Most cases identified in Lilly’s trial were mild.
According to the FDA, three drug-related deaths occurred in the donanemab study, all due to brain inflammation or hemorrhage. One of the deaths was due to a stroke, a potentially fatal complication that is more common among Alzheimer’s patients.
The FDA expert group agreed that the risks could be addressed through warning labels and training of doctors, as well as through medical scans to identify patients at highest risk for stroke.
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