Eli Lilly’s Alzheimer’s drug slows progression, carries risk of brain swelling, bleeding, study says
Another experimental Alzheimer’s drug could modestly slow patients’ inevitable deterioration — by about four to seven months, researchers reported Monday.
Eli Lilly and Co. seeks U.S. Food and Drug Administration (FDA) approval for donanemab. If approved, it would be only the second Alzheimer’s treatment conclusively shown to slow the brain-ravaging disease — after Japanese drugmaker Eisai’s recently approved Leqembi.
“Finally there’s some hope, right, that we can talk about,” Lilly’s Dr. John Sims to reporters on Monday at the Alzheimer’s Association International Conference in Amsterdam.
“We don’t cure the disease,” he said. “Diabetes also has no cure. It doesn’t mean you can’t have meaningful treatments for patients.”
Lilly announced in May that donanemab seemed to be working, but on Monday the full results of a study of 1,700 patients were published by the Journal of the American Medical Association (JAMA) and presented at the Alzheimer’s conference.
Both donanemab and Leqembi are lab-made antibodies, administered by IV, that target one Alzheimer’s culprit: sticky amyloid buildup in the brain. And both drugs pose a serious safety concern: brain swelling or bleeding that was linked to three deaths in the Lilly study.
Leqembi and donanemab are not approved in Canada.
In an email to CBC News, a Health Canada spokesperson said Leqembi is listed as under review on the agency’s new drug submission website. The drug’s application was accepted for review in May.
Health Canada says it does not comment on drugs under review, and the timing of these submissions depends on many factors, including the need for more data, discussions with the sponsor and requirements for safety information updates.
Meanwhile, donanemab has not been submitted for review, according to Health Canada’s website.
Questions remain about which patients will benefit
Scientists say that while these drugs could usher in a new era in Alzheimer’s treatment, big questions remain about which patients
should they try and how much benefit they will really notice.
“The modest benefits would probably not be questioned by patients, clinicians or payers if amyloid antibodies were low risk, cheap and easy to administer. However, they are not,” says Dr. Eric Widera of the University of California, San Francisco, wrote in a JAMA editorial accompanying Lilly’s new data.
Lilly’s study included people ages 60 to 85 who were in the early stages of Alzheimer’s disease. Half received infusions of donanemab once a month for 18 months and the other half received sham infusions.
The study had a few twists. Patients were switched to dummy infusions when enough amyloid cleared — something that happened to about half within a year.
And because amyloid alone doesn’t cause Alzheimer’s, researchers also tracked levels of another culprit in the brain — abnormal tau. More tau indicates a more advanced disease.
The results: Both groups deteriorated during the 18-month study, but overall those who received donanemab deteriorated about 22 percent more slowly. Some patients fared better — those with low to medium tau levels saw a 35 percent slower decline, indicating that the drug seems to work better in earlier stages of the disease.
LOOK | New Alzheimer’s drug Leqembi met with hope and caution:
Two drug companies say a drug they’ve developed has the potential to slow the progression of Alzheimer’s disease, something no treatment has been able to do. Now researchers and those affected by the disease are anxiously awaiting the full results of a human trial for the medication.
The drug slows the progression of the disease by 4 to 7 months
How much difference does that make? It means donanemab slowed the patients’ deterioration by about four to seven months, the JAMA report concluded.
Another way of measuring: Of the donanemab recipients with lower tau levels, 47 percent were considered stable after a year of participation in the study, compared to 29 percent of those who received the dummy version.
The main safety concern is swelling or bleeding of the brain, which often causes no symptoms but can sometimes be serious and even fatal. About a quarter of donanemab recipients showed signs of that swelling, and about 20 percent had microbleeds.
Scientists already know that patients receiving amyloid-targeted therapy need repeat brain scans to monitor it
side effects — a costly and time-consuming hurdle.
Widera noted that the ability to at least temporarily stop donanemab treatment in people who respond well would help mitigate some of those challenges. In comparison, Leqembi is given by an IV every two weeks, and researchers have not tested a similar interruption.
It’s too early to know if some patients should resume donanemab, said Lilly’s Dr. Mark Mintun.
But the amyloid “isn’t coming back with any sort of retaliation,” he said, speculating it could take several years.
Lack of diversity in study
Another concern: More than 90 percent of the study participants were white, leaving little data on how other populations might respond, Columbia University Alzheimer’s specialist Jennifer Manly wrote in JAMA.
Scientists have long tried to slow Alzheimer’s with amyloid-targeted drugs, but failed — and the controversial 2021 FDA conditional approval of a drug called Aduhelm soon fizzled out for lack of evidence that it actually worked. Leqembi’s approval and promising data for donanemab have reignited interest in attacking amyloid buildup.
But Mintun acknowledged additional approaches are needed, saying Lilly expects results next year from a late-stage study of a tau-fighting drug.
