FDA advisers agree that lecanemab shows benefit as an Alzheimer’s treatment
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A US Food and Drug Administration advisory panel unanimously ruled Friday that the Alzheimer’s drug lecanemab shows “clinical benefit” for treating the disease, paving the way for the drug to be considered for full FDA approval.
A decision from the FDA is expected by July 6.
Lecanemab, a monoclonal antibody sold under the brand name Leqembi, is one of the first dementia drugs that appears to slow the progression of cognitive decline. The drug is not a cure, but works by binding to amyloid beta, a hallmark of Alzheimer’s disease.
In January, the FDA granted accelerated approval of Leqembi for people with mild cognitive impairment or mild dementia, although there were some safety concerns due to the treatment’s association with certain serious side effects, including brain swelling and bleeding.
The accelerated approval program allows for earlier approval of drugs that treat serious conditions and “fill an unmet medical need” while researchers continue to study the drug to confirm, verify and describe its clinical benefit. If these additional studies show a benefit, the FDA may grant traditional full approval for the drug. However, if the confirmatory studies do not show benefits, the drug may be taken off the market.
If lecanemab receives traditional FDA approval, the federal Centers for Medicare and Medicaid Services has said it would provide broader coverage — meaning Medicare patients could have greater access to the treatment. However, the coverage will come with some qualifications.
“If the FDA grants traditional approval, CMS is prepared to ensure that everyone with Medicare Part B who meets the criteria is covered,” CMS Administrator Chiquita Brooks-LaSure said in a statement this month.
Medicare will cover the approved drugs when a doctor and a clinical team participate in gathering evidence about how those drugs work in the real world, also known as a registry, CMS said. Suppliers will be able to submit the evidence through a CMS-facilitated portal.
However, patient groups and the pharmaceutical industry have expressed concern about the use of a registry, saying it would create a barrier to treatment.
“If Leqembi is granted approval for broad coverage, it could mean that those on Medicare would have the option to pursue treatment, which would mean a significant increase in Medicare costs and a potentially difficult path for patients hoping to qualify for treatment ” Michael Abrams, managing partner at global healthcare consulting firm Numerof & Associates, said in an email Friday. He was not involved in the FDA advisory committee’s vote, but has closely followed discussions surrounding lecanemab.
The committee’s support for lecanemab serves as an “important milestone” in the pursuit of possible full FDA approval, experts say.
“The vote of support for Lecanemab is an important milestone for every patient living with Alzheimer’s disease, every family with a loved one affected by Alzheimer’s disease, and indeed all people at risk of developing Alzheimer’s disease in the future,” Dr. James Galvin , chief of cognitive neurology and director of the Comprehensive Center for Brain Health at UHealth – University of Miami Health System, said in an email Friday. He was not involved in the FDA committee meeting.
“It has been nearly two decades since the last Alzheimer’s treatment received full FDA approval, and never before has a disease-modifying drug received full FDA approval,” he wrote. “This vote today will almost certainly be followed by two important decisions – full FDA approval and agreement by CMS to cover treatment in some form. This is a critical issue to ensure that all patients from all social and economic backgrounds have access to medicines.”
What the science says about lecanemab
On Friday, the FDA’s Advisory Committee on Drugs in the Peripheral and Central Nervous System met to discuss the results of a confirmatory phase 3 study on lecanemab, as drugmaker Eisai seeks full approval. In the end, members voted 6-0 in favor of the drug’s clinical benefit.
“We will consider whether any of the new data affects our current understanding of the safety of lecanemab and the benefit-risk assessment,” Dr. Teresa Buracchio, acting director of the FDA’s Office of Neuroscience, said at Friday’s meeting.
In the study, 897 participants were given a placebo and 898 were given lecanemab, administered every two weeks as an intravenous infusion. The study found that 18 months later, lecanemab slowed disease progression by at least 26% in certain measurements, according to data Eisai presented to the FDA’s advisory panel on Friday.
“I thought the evidence for clinical benefit was very clear, very robust,” Dr. Merit Cudkowicz, chief of neurology at Massachusetts General Hospital and a member of the FDA’s advisory committee, said at the meeting. Many of the other members agreed.
The data also showed that 26% of participants who received lecanemab had infusion-related reactions, compared with 7% of those who received placebo. Among lecanemab recipients, 17% had brain bleeding, compared with 9% in the placebo group, and 13% had brain swelling, compared with 2% who received placebo.
“These tended to occur early in treatment, and supported monitoring during the first six months of treatment,” Dr. Michael Irizarry, senior vice president and vice president for Alzheimer’s disease and brain health at Eisai, told the FDA committee on Friday.
The potential for side effects can affect the drug’s coverage, Abrams said. “Although Leqembi slowed cognitive decline in early Alzheimer’s patients by 27% in the study, the treatment also carries serious risks of brain swelling and bleeding,” he said. “There may be reason for CMS to impose conditions on its use, limiting the number of patients who will qualify (at least initially) and reducing the potential $5B cost of the program.”
In a previous study, about 6.9% of study participants who received lecanemab dropped out because of side effects, compared with 2.9% of those who received a placebo. Overall, there were serious side effects in 14% of the lecanemab group and 11.3% of the placebo group.
The most common side effects in the lecanemab group were reactions to intravenous infusions and abnormalities on their MRIs, such as brain swelling and bleeding, also known as amyloid-related imaging abnormalities, or ARIA, which can be life-threatening. The drug’s prescribing information contains a warning about ARIA, the FDA says.
Some people who get ARIA may not have symptoms, but it can occasionally lead to hospitalization or permanent debilitation. And the rate of ARIA appeared to be higher in people who had a gene called APOE4, which can increase the risk of Alzheimer’s disease or other dementias. ARIA “was numerically less common” among APOE4 non-carriers.
The FDA’s advisory committee on Friday discussed concerns about lecanemab’s overall risks versus benefits for APOE4 carriers. “The ARIA rate was quite striking,” committee member Dr. Michael Gold said at Friday’s meeting.
More than 6.5 million people in the United States are living with Alzheimer’s disease, according to the Alzheimer’s Association, and that number is expected to grow to 13.8 million by 2060.
CNN’s Tami Luhby contributed to this report.
