July 7, 2023 – Experts in the sphere of Alzheimer's disease are throwing around terms like “breakthrough,” “celebration,” and “excited,” in the future after the FDA granted full approval for a recent 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 unwanted effects, corresponding to brain swelling or bleeding, which prompted the FDA to require a boxed warning on the drug's label.
Price may be a consideration. Lecanemab costs an estimated $26,500 per 12 months, which drugmaker Eisai justifies by saying that every patient treated 37,600 US dollars “Value per patient per year“ for 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, answered 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 meaningful lives.”
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 adverse events or side effects associated with the treatment. That's why it comes with what's called a black box warning,” Weiner said.
The FDA's boxed warning is taken into account the best 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 unwanted effects include microbleeds and brain swelling.
Peschin said it's vital for the general public to learn about these risks and discuss them with their doctors. The risks are “minimal for many people,” she said, but added that individuals with two copies of a genetic mutation called APOE4 are at higher risk for these unwanted effects.
The boxed warning is meant to lift awareness of a few of these unwanted effects, Edemayer said. “We very much welcome the fact that these discussions take place between individuals or families and physicians so that they can 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 due to risk of bleeding. While it's not an official FDA warning, “if you're taking a blood thinner, a microbleed can turn out to be a macrobleed.”
A variety of large bleeding within the brain, which may be extremely serious, he explained. There have been just a few people taking a monoclonal antibody like leqembi or aducanumab who've 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 may be 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 make a suggestion for approval. The FDA isn't sure by the Advisory Board's decisions, but normally follows their guidelines.
Lecanemab targets the underlying reason for Alzheimer's disease. The treatment reduced the quantity of amyloid plaques within the brain, the buildup of which I even have long believed to be a serious reason for the memory-robbing disease.
Treatment is given twice a month as an intravenous infusion. Weiner hopes that a more convenient tablet form will likely be available in the longer term.
Medicare coverage, with a catch
If you're a Medicare patient, the plan will cover 80% of your drug costs. However, you have to first meet just a few requirements. The first is clear: you have to be enrolled in Medicare.
However, the Centers for Medicare and Medicaid Services also requires that you've gotten a diagnosis of mild cognitive impairment or mild Alzheimer's dementia and that you've gotten documented evidence of beta-amyloid plaques within the brain. “That's critical because you don't want 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 care for this final requirement.
A glance ahead
The pharmaceutical company Lilly has accomplished a Phase III study on a monoclonal antibody for the treatment of Alzheimer's disease. The antibody is known as donanemab and is predicted 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 think that in our lifetime we will see the opportunity to prevent cognitive decline and dementia by identifying people who think they are 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 more often than not people show no symptoms in any respect.
“It’s just like early stage prostate cancer or early stage breast cancer,” he said.
However, research is underway that can use scans to discover individuals who have amyloid plaques but don't know they've Alzheimer's, after which treat them with monoclonal antibody therapy to stop the disease. Stay tuned.
The Alzheimer's Association encourages individuals with Alzheimer's disease and their providers to incorporate information of 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 wide selection of treatments for Alzheimer's disease to support education, clinical care and research.