July 7, 2023: Experts in the field of Alzheimer’s disease are releasing works like “breakthrough,” “celebrate,” and “excited,” a day later the fda granted full approval of a new drug to treat the early stages of the disease.
With no cure in sight, any new approval brings hope, even with an agent like Leqembi that slowed disease progression by an average of 27% under investigation. Concerns include reports of some rare but potentially serious side effects, such as swelling or bleeding in the brain, prompting the FDA to require a boxed warning on the drug’s label.
Price could also be a consideration. Lecanemab is estimated to cost $26,500 per year, which the drugmaker Eisai justifies by saying that each patient treated has a $37,600 “per patient per year of value” for society.
Lecanemab is intended to slow progression in people with mild thinking and memory problems in early Alzheimer’s disease. It is not a cure and it does not reverse the progress of people already living with more advanced disease.
The first of its kind
“This is the first traditional approval for an Alzheimer’s disease-modifying therapy. That’s a huge win for patients and their families,” said Susan Peschin, president and CEO of the nonprofit Alliance for Aging Research. She added that the Alliance is “delighted” that this agent has gained full FDA approval.
“We know that it is not a cure or even a therapy that is going to have a significant lasting effect. But having a therapy that slows the progression of early Alzheimer’s disease by 27 percent over 18 months, that could mean a lot for people who have mild cognitive impairment,” Peschin said.
After a year and a half of taking the drug, Leqembi delayed Alzheimer’s disease symptoms by more than 5 months compared to placebo.
When asked if this is likely to make a difference in people’s daily lives, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said yes. An additional 5.3 months of delayed progression compared to placebo in the research “will be very valuable to an individual at an early stage. It means more time with family, attending graduations and being independent…so they can continue to lead meaningful lives.”
Now there is hope for people with early Alzheimer’s disease, said Michael Weiner, MD, professor of radiology and biomedical imaging, medicine, psychiatry and neurology at the University of California, San Francisco. “The big picture is that this is a breakthrough.”
If you or a loved one may be or are in the early stages, “now is the time to go see a doctor for evaluation,” said Weiner, who is also a principal investigator for the Alzheimer’s Disease Neuroimaging Initiative. , the world’s largest observational study for Alzheimer’s.
“If people wait too long, the door may close.”
How safe is the treatment?
“There are definitely adverse events or side effects associated with the treatment. That’s why it carries what’s called a black box warning,” Weiner said.
The FDA’s boxed warning is considered the highest safety-related warning for risks of “serious and life-threatening events.” The concern with Leqembi and other drugs used to treat Alzheimer’s disease is amyloid-related imaging abnormalities (ARIA) in the brain. Side effects of ARIA include microbleeding and brain swelling.
Peschin said it’s important for the public to be aware of these risks and discuss them with their doctors. The risks are “minimal for many people,” she said, but added that people with two copies of a gene mutation called APOE4 are at higher risk of these side effects.
The boxed warning is intended to draw attention to some of these side effects, Edemayer said. “We really appreciate those discussions taking place between individuals or families and doctors so they can make forced treatment decisions.” She added that many drugs to treat other conditions carry FDA warnings.
Weiner cautioned against using Leqembi in people taking blood thinners because of the risk of bleeding. It’s not an official FDA warning, “but if you’re taking a blood thinner, a microbleed can turn into a macrobleed.”
A lot of large bleeding in the brain that can be extremely serious, he explained. There have been a few people, just a few, taking a monoclonal antibody like Leqembi or aducanumab who have experienced seizures, hospitalization, or death.
an unmet need
Full approval was largely expected. The FDA granted Leqembi accelerated approval in January after an early study suggested it might slow disease progression. The agency grants expedited approval when there is an unmet need and a drug shows early promise while larger studies are underway. In this case, a second study confirmed clinical benefit and the FDA granted full approval.
Also, last month, the FDA Advisory Group reviewed the evidence for Leqembi voted unanimously to recommend approval. The FDA is not bound by the decisions of the advisory board, but generally follows its guidance.
Lecanemab addresses the underlying cause of Alzheimer’s disease. The treatment reduced levels of amyloid plaques in the brain, the buildup of which has long been considered a major culprit in memory steal disease.
Treatment is administered as intravenous infusions twice a month. Weiner hopes that a more convenient pill form will become available in the future.
Medicare coverage, with a catch
Also, if you are a Medicare patient, the plan will cover 80% of your drug costs, but you must meet certain requirements first. The first is obvious: you must be enrolled in Medicare.
But the Centers for Medicare & Medicaid Services also requires you to have a diagnosis of mild cognitive impairment or mild dementia from Alzheimer’s disease, with documented evidence of beta-amyloid plaques in the brain. “That’s critical, you don’t want to treat someone who isn’t living with Alzheimer’s disease,” Edelmayer said.
Your doctor must also enroll in a CMS-approved registry to enter patient data and receive reimbursement for care. Your doctor will take care of this last requirement.
A look to the future
Drug maker Lilly has completed a Phase III study of a monoclonal antibody under development for Alzheimer’s disease. It’s called donanemab and it’s expected to be reviewed by the FDA soon.
Another monoclonal antibody, already approved by the FDA for Alzheimer’s, is Aduhelm. The June 2021 approval was controversial. All members of the FDA Advisory Council voted against its approval.
Weiner offered an optimistic overall outlook.
“I think in our lifetime, we are going to see the ability to prevent cognitive decline and dementia by identifying people who think they are completely normal and treating them before they develop symptoms,” he said.
Alzheimer’s disease, which affects 6.5 million Americans, typically develops over 15 years and most of that time, people don’t have any symptoms.
“It’s like early stage prostate cancer or early stage breast cancer,” he said.
But there is ongoing research using scans to identify people who have amyloid plaques but don’t know they have Alzheimer’s disease and treating 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 enter information into their Alzheimer’s Network for Diagnosis and Treatment (ALZ-NET) record. Launched in 2021, it aims to collect robust information on the safety and efficacy of a wide range of Alzheimer’s disease treatments to inform education, clinical care, and research.