WASHINGTON — (TodayNews) — Another experimental Alzheimer’s drug could slightly slow the inevitable deterioration in patients’ conditions by about four to seven months, researchers said Monday.
Eli Lilly and Co. is seeking FDA approval for donanemab. If approved, it would be only the second Alzheimer’s drug that has been convincingly shown to delay the mind-bending disease, following the recently approved drug Lekambi from Japanese drug maker Eisai.
“Finally, there is hope that we can talk about,” Lilly’s Dr. John Sims told reporters Monday at the Alzheimer’s Association International Conference in Amsterdam.
“We don’t cure the disease,” he said. “Diabetes is also incurable – that doesn’t mean you can’t have very meaningful treatments for patients.”
Lilly announced in May that donanemab appeared to be working, but on Monday, the full results of a study of 1,700 patients were published in the Journal of the American Medical Association and presented at the Alzheimer’s Conference.
Both donanemab and Lekambi are intravenous laboratory antibodies that target one of the causes of Alzheimer’s disease, the buildup of sticky amyloid in the brain. And both drugs are associated with a major safety concern — cerebral edema or bleeding — which was linked to three deaths in Lilly’s study.
Scientists say that while these drugs could usher in a new era in Alzheimer’s treatment, huge questions remain about which patients should try them and what benefits they will actually see.
“The modest benefits would probably not be questioned by patients, clinicians, or payers if amyloid antibodies were low-risk, inexpensive, and easy to administer. However, they are none of them,” wrote Dr. Eric Wiedera of the University of California, San Francisco, in a JAMA editorial accompanying Lilly’s new data.
Lilly’s study included people aged 60 to 85 who had early stage Alzheimer’s disease. Half of them received donanemab infusions once a month and half received dummy infusions for 18 months.
The study had several twists and turns. Patients were switched to sham infusions if enough amyloid was cleared out, which happened about half the time within a year. And because amyloid by itself does not cause Alzheimer’s, the researchers also monitored levels of another culprit in the brain, abnormal tau. More tau signals more advanced disease.
Results. Both groups deteriorated over the course of the 18-month study, but overall, those who received donanemab deteriorated about 22% more slowly. Some patients felt better—those with low to moderate tau experienced a 35% slower decline, suggesting that the drug appears to work better in the earlier stages of the disease.
Who cares? This means that donanemab slowed patients’ deterioration by about four to seven months, according to the JAMA report.
Another way to measure it: among donanemab recipients with lower tau levels, 47% were considered stable after one year of the study compared to 29% of those who received the sham version.
The main safety concern is cerebral swelling or bleeding, which often causes no symptoms but can sometimes be severe and even fatal. About a quarter of donanemab recipients showed signs of this edema, and about 20% had microbleeds.
Scientists already know that patients receiving any therapy that targets amyloid need a second brain scan to check for these side effects — a costly and time-consuming hurdle.
Wiedera noted that being able to stop donanemab treatment, at least temporarily, in people who respond well would help limit some of these problems. In comparison, Lekambi is administered intravenously every two weeks, and the researchers did not test for such a stop.
It’s too early to say that some patients may need to restart donanemab, said Dr. Mark Mintan of Lilly. But the amyloid “is not coming back with any vengeance,” he said, suggesting it could take several years.
Another issue: More than 90% of the study participants were white, leaving little evidence of how other populations might react, Alzheimer’s expert Jennifer Manley of Columbia University wrote in JAMA.
Scientists have long tried to slow Alzheimer’s with amyloid-targeting drugs without success, and a controversial 2021 FDA conditional approval of a drug called Aduhelm soon fell through due to lack of evidence that it actually works. The approval of Lekambi and promising data from donanemab have revived interest in combating amyloid accumulation.
But Mintoon acknowledged that additional approaches are needed, saying Lilly is awaiting the results of the latest phase of the tau drug trial next year.
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