July 7, 2023 – Experts in the sector of Alzheimer's disease are throwing around terms like “breakthrough,” “celebration,” and “excited,” in the future after the FDA granted full approval for a brand new drug to treat early stages of the disease.
With no cure in sight, each recent approval brings recent hope, even for a drug like Leqembi, which in trials slowed disease progression by a mean of 27 percent. Concerns include reports of some rare but potentially serious uncomfortable side effects, comparable to brain swelling or bleeding, which prompted the FDA to require a boxed warning on the drug's label.
Price is also a consideration. Lecanemab costs an estimated $26,500 per yr, which drugmaker Eisai justifies by saying that every patient treated 37,600 US dollars “Value per patient per year” for the society.
Lecanemab is intended to slow the progression of Alzheimer's disease in patients with mild early-stage thinking and memory problems. It is not a cure for patients with advanced disease, nor can it reverse the progression of the disease.
The first of its kind
“This is the first conventional approval for a disease-modifying therapy for Alzheimer's, so this is a huge win for patients and families,” said Susan Peschin, president and CEO of the nonprofit Alliance for Aging Research. She added that the Alliance was “thrilled” that this drug had received full FDA approval.
“We know it's not a cure or a therapy with long-term effects. But having a therapy that slows the progression of early Alzheimer's disease by 27% within 18 months could mean a lot for people with mild cognitive impairment,” Peschin said.
After a year and a half of taking the drug, Leqembi delayed the symptoms of Alzheimer's disease by more than five months compared to a placebo.
When asked if it would make a difference in people's everyday lives, Dr. Rebecca Edelmayer, senior director of scientific engagement at the Alzheimer's Association, said yes. An additional 5.3 months' delay in disease progression compared to placebo in research “is going to be very valuable to a person at an early stage. It means more time with family, attending graduation ceremonies and independence … so they can continue to live a meaningful life.”
There is now hope for people with early-stage Alzheimer's, said Dr. Michael Weiner, professor of radiology and biomedical imaging, medicine, psychiatry and neurology at the University of California, San Francisco. “Overall, this is a breakthrough.”
If you or a loved one may be in the early stages of the disease, “now is the time to go to a doctor and get checked,” says Weiner, who is also principal investigator of the Alzheimer's Disease Neuroimaging Initiative, the world's largest observational study of Alzheimer's.
“If people wait too long, the door could close.”
How protected is the treatment?
“There are definitely hostile events or uncomfortable side effects related to the treatment. That's why it comes with what's called a black box warning,” Weiner said.
The FDA's boxed warning is considered the highest safety warning, about risks of “serious and life-threatening events.” The concern with Leqembi and other drugs used to treat Alzheimer's disease is amyloid-related brain imaging abnormalities (ARIA). ARIA side effects include microbleeds and brain swelling.
Peschin said it's important for the public to know about these risks and discuss them with their doctors. The risks are “minimal for many individuals,” she said, but added that people with two copies of a genetic mutation called APOE4 are at higher risk for these side effects.
The boxed warning is intended to raise awareness of some of these side effects, Edemayer said. “We very much welcome the incontrovertible fact that these discussions happen between individuals or families and physicians in order that they’ll make binding treatment decisions.” She added that many drugs used to treat other conditions carry boxed warnings from the FDA.
Weiner warned against using Leqembi in people taking blood-thinning medications because of the risk of bleeding. While it's not an official FDA warning, “should you're taking a blood thinner, a microbleed can turn into a macrobleed.”
A lot of large bleeding in the brain, which can be extremely serious, he explained. There have been a few people taking a monoclonal antibody like leqembi or aducanumab who have experienced seizures, hospitalizations or deaths.
An unfulfilled need
Full approval had been widely expected. The FDA granted Leqembi accelerated approval in January after an initial study suggested it could slow disease progression. The agency grants accelerated approval when there is an unmet need and a drug shows initial promise while larger trials are being conducted. In this case, a second trial confirmed the clinical benefit and the FDA granted full approval.
In addition, last month the FDA advisory group reviewed the evidence for Leqembi unanimously decided to recommend approval. The FDA is not bound by the advisory committee's decisions, but usually follows its guidelines.
Lecanemab targets the underlying cause of Alzheimer's disease. The treatment reduced the amount of amyloid plaques in the brain, the buildup of which I have long believed to be a major cause of the memory-robbing disease.
Treatment is given twice a month as an intravenous infusion. Weiner hopes that a more convenient tablet form will be available in the future.
Medicare coverage, with a catch
If you are a Medicare patient, the plan will cover 80% of your drug costs. However, you must first meet a few requirements. The first is obvious: you must be enrolled in Medicare.
However, the Centers for Medicare and Medicaid Services also requires that you have a diagnosis of mild cognitive impairment or mild Alzheimer's dementia and that you have documented evidence of beta-amyloid plaques in the brain. “That's critical since you don't need to treat someone who doesn't have Alzheimer's,” Edelmayer said.
Your doctor must also enroll in a CMS-approved registry to enter patient data and receive reimbursement for treatment. Your doctor will take care of this final requirement.
A look ahead
The pharmaceutical company Lilly has completed a Phase III study on a monoclonal antibody for the treatment of Alzheimer's disease. The antibody is called donanemab and is expected to be reviewed by the FDA soon.
Another monoclonal antibody that has already been approved by the FDA for Alzheimer's is Aduhelm. Its approval in June 2021 was controversial. All members of the FDA advisory committee voted against approval.
Weiner offered an optimistic overall perspective.
“I believe that in our lifetime we are going to see the chance to stop cognitive decline and dementia by identifying individuals who think they’re perfectly normal and treating them before they develop symptoms,” he said.
Alzheimer's disease, which affects 6.5 million Americans, typically develops over a 15-year period, and most of the time people show no symptoms at all.
“It’s just like early stage prostate cancer or early stage breast cancer,” he said.
However, research is underway that will use scans to identify people who have amyloid plaques but don't know they have Alzheimer's, and then treat them with monoclonal antibody therapy to prevent the disease. Stay tuned.
The Alzheimer's Association encourages people with Alzheimer's disease and their providers to include information in their Alzheimer's Network for Treatment and Diagnostics (ALZ-NET) Launched in 2021, the registry goals to gather robust information on the protection and effectiveness of a big selection of treatments for Alzheimer's disease to support education, clinical care and research.