Alzheimer's drug slows down the disease, but comes with risks: study
Company is seeking U.S. Food and Drug Administration approval of donanemab
Another experimental Alzheimer's drug can modestly slow patients' inevitable worsening — by about four to seven months, researchers reported Monday.
Eli Lilly and Co. is seeking U.S. Food and Drug Administration (FDA) approval of donanemab. If cleared, it would be only the second Alzheimer's treatment convincingly shown to delay the mind-robbing disease, after the recently approved Leqembi from Japanese drugmaker Eisai.
"Finally there's some hope, right, 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 doesn't have a cure either. It doesn't mean you can't have very meaningful treatments for patients."
Lilly announced in May that donanemab appeared to work, 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. Both drugs come with a serious safety concern — brain swelling or bleeding that in the Lilly study was linked to three deaths.
Leqembi and donanemab are not approved in Canada.
In an email to CBC News, a Health Canada spokesperson said that 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 doesn't comment on drugs that are under review, and that timing of these submissions depends on many factors, including a need for more data, talks with the sponsor and requirements for updates to safety information.
Meanwhile, donanemab has not been submitted for review, according to Health Canada's website.
The Alzheimer Society of Canada's CEO Christopher Barry told CBC News in an email that the society is "hopeful that new advancements in research will bring more treatment options to Canadians."
Barry added that long-term trial data will be crucial in understanding the risks and benefits for people living with dementia.
Questions remain about which patients will benefit
Scientists say while these drugs may mark a new era in Alzheimer's therapy, huge questions remain about which patients
should try them and how much benefit they'll really notice.
"The modest benefits would likely not be questioned by patients, clinicians or payers if amyloid antibodies were low risk, inexpensive and simple to administer. However, they are none of these," Dr. Eric Widera, of the University of California, San Francisco, wrote in a JAMA editorial accompanying Lilly's new data.
Lilly's study enrolled people aged 60 to 85 who were in early stages of Alzheimer's. Half received once-a-month infusions of donanemab and half got dummy infusions for 18 months.
The study had a few twists. Patients were switched to dummy infusions if enough amyloid cleared out — 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 signals more advanced disease.
The results: both groups declined during the 18-month study, but overall, those given donanemab worsened about 22 per cent more slowly. Some patients fared better — those with low to medium tau levels saw a 35 per cent slower decline, reflecting that the drug appears to work better in earlier stages of the disease.
WATCH | New Alzheimer's drug Leqembi met with hope and caution:
Drug slows disease progression by 4 to 7 months
How much difference does that make? It means donanemab slowed patients' worsening by about four to seven months, the JAMA report concluded.
Another way of measuring: among the donanemab recipients with lower tau levels, 47 per cent were considered stable a year into the study compared with 29 per cent of those who got the dummy version.
The main safety concern is brain swelling or bleeding, which often causes no symptoms but sometimes can be serious, even fatal. About a quarter of donanemab recipients showed evidence of that swelling, and about 20 per cent had microbleeds.
Scientists already know that patients getting any amyloid-targeted therapy need repeat brain scans to check for those
side effects — a costly and time-consuming hurdle.
Widera noted that the possibility of stopping donanemab treatment at least temporarily in people who respond well would help limit some of those challenges. For comparison, Leqembi is given by IV every two weeks and researchers didn't test a similar stoppage.
It's too soon to know if some patients might need to resume donanemab, said Lilly's Dr. Mark Mintun.
But the amyloid "doesn't come back with any sort of vengeance," he said, speculating that might take several years.
Canada's health-care system 'not ready,' expert says
Neurologist Carmela Tartaglia, with the University Health Network's Krembil Brain Institute in Toronto, told CBC News that while the findings are "very promising," it's important people know that it's not a "miracle" and "doesn't stop the disease altogether."
But the delay it creates, Tartaglia said, can give people some extra time with a loved one.
"Keeping people out of nursing homes is very much clinically meaningful for our patients," she said. "Even if it's only six months — and that seems like not that much for us in the bigger scheme of a lifetime — six months extra with a loved one is actually hugely meaningful for many of our patients and their families."
She said this drug still comes with its limitations, however, such as whether the plaque will eventually return after patients stop the medication.
When it comes to the future of a drug like this in Canada, Tartaglia suggested our health system is "not ready" for this type of treatment.
People approved for the drug need to be specifically diagnosed and tested, they'll need to get infusions and will then need to be monitored with constant MRIs — all of this, she said, can't be handled by our current health-care system.
"I think the drugs have shown their efficacy," she said. "The problem is to get the right drug to the right person at the right time; the infrastructure in [the] Canadian health care system has to change."
Lack of diversity in study
Another concern with the study on donanemab is that more than 90 per cent of its participants were white, leaving little data about how other populations might respond, Alzheimer's specialist Jennifer Manly, of Columbia University, wrote in JAMA.
Scientists have long tried and failed to slow Alzheimer's with amyloid-targeting drugs — and the FDA's contentious 2021 conditional approval of a drug named Aduhelm soon fizzled amid lack of evidence that it really worked. The approval of Leqembi and promising data for donanemab have reignited interest in attacking amyloid buildup.
But Mintun acknowledged additional approaches are needed, saying Lilly expects results of a late-stage study of a tau-fighting drug next year.
With files from CBC's Jennifer La Grassa and Melanie Glanz
