Alzheimer’s drug lecanemab receives accelerated FDA approval due to safety concerns
CNN
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The US Food and Drug Administration granted accelerated approval on Friday for the Alzheimer’s disease drug lecanemab, one of the first experimental dementia drugs that appears to slow the progression of cognitive decline.
“Alzheimer̵[ads1]7;s disease makes the lives of those who suffer from it immeasurably incapacitating and has devastating effects on their loved ones,” said Dr. Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, rather than just treating the symptoms of the disease.”
Lecanemab will be marketed as Leqembi, the FDA statement says. It has shown “potential” as a treatment for Alzheimer’s disease by appearing to slow its progression, according to results from phase 3 trials, but it has raised safety concerns because of its association with certain serious side effects, including brain swelling and bleeding.
In July, the FDA accepted Eisai’s Biologics License Application for lecanemab under the accelerated approval pathway and granted drug priority review, according to the company. The accelerated approval program allows for earlier approval of drugs that treat serious conditions and “fill an unmet medical need” while the drugs continue to be studied in larger and longer studies.
If these trials confirm that the drug provides a clinical benefit, the FDA may grant traditional approval. But if the confirmatory trial doesn’t show benefit, the FDA has the regulatory procedures that could lead to the drug being taken off the market.
Lecanemab, a monoclonal antibody, is not a cure, but works by binding to amyloid beta, a hallmark of Alzheimer’s disease. In late November, results from an 18-month phase 3 clinical trial published in The New England Journal of Medicine showed that lecanemab “reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline in measures of cognition and function than placebo at 18 years. months, but was associated with adverse events.”
The results also showed that about 6.9% of study participants who received lecanemab, as an intravenous infusion, discontinued the study due to adverse events, compared with 2.9% of those who received 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 called amyloid-related imaging abnormalities, or ARIA, which can be life-threatening.
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 study showed.
The drug’s prescribing information contains a warning about ARIA, the FDA says.
The trial results also showed that around 0.7% of participants in the lecanemab group and 0.8% of those in the placebo group died, corresponding to six deaths in the lecanemab group and seven in the placebo group.
The Alzheimer’s Association welcomed Friday’s decision.
“By slowing the progression of the disease when caught in the early stages of Alzheimer’s, individuals will have more time to participate in daily life and live independently,” said President and CEO Joanne Pike. “This can mean more months of acknowledging one’s spouse, children and grandchildren. It can also mean more time for a person to drive safely, accurately and quickly, take care of family finances, and participate fully in hobbies and interests.”
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.
Lecanemab will have a wholesale price of $26,500 per patient per year, the drug’s makers announced Friday.
Biogen and Eisai have listed the drug slightly below the reduced price of the Alzheimer’s drug Aduhelm, which now costs the average patient about $28,200. The companies had to lower the cost of Aduhelm — initially set at $56,000 per patient per year — after insurers refused to cover it.
To justify the cost of Leqembi, the companies said in a press release that based on the estimated quality of life achieved by people taking it, the value of the medicine to society is around $37,000 a year, but they chose to go lower “to aim to promote wider patient access, reduce overall financial burden and support health system sustainability.”
The wholesale cost of a drug is akin to a car’s sticker price. It is not necessarily what patients pay after insurance or other discounts are taken into account.
However, insurance coverage for this medication is not provided. Medicare limited coverage of lecanemab’s sister drug, Aduhelm, after clinical trials showed questionable benefits for patients. The agency agreed to cover the drug only for people enrolled in registered clinical trials, limiting access to the medicine.
Centers for Medicare and Medicaid Services Administrator Chiquita Brooks-LaSure said after the FDA’s decision Friday that her office would quickly review Leqembi, but for now, because of the accelerated approval, it will be covered the same way Aduhelm is covered.
“At CMS, we will continue to rapidly review the data on these products as they become available and are committed to timely access to treatments, including medications, that improve clinically meaningful outcomes,” Brooks-LaSure said in a statement.
Last month, the Alzheimer’s Association submitted a formal request asking CMS to provide “full and unlimited coverage” of Alzheimer’s treatments approved by the FDA.
“What the FDA did today in granting accelerated approval to Leqembi was the right decision. But what CMS is doing by severely limiting coverage for approved treatments is unprecedented and wrong,” Pike said in a statement Friday.
“FDA carefully reviewed the evidence for Leqembi before granting approval. CMS, in stark contrast, denied coverage for Leqembi months ago before it had even reviewed this drug’s evidence. CMS has never done this before for any drug, and it is clearly harmful and unfair to those with Alzheimer’s. Without access and coverage of this treatment and others in its class, people lose days, weeks, months – memories, skills and independence. They lose time.”
CMS told CNN it will review and respond to the association’s request. The agency also noted that it continues to stay informed about ongoing clinical trials, including the latest lecanemab results published in the New England Journal of Medicine. It has also met with drug manufacturers to learn about their efforts since CMS’s coverage decision was announced.
The FDA approved Aduhelm for early stages of Alzheimer’s disease in 2021 — but that decision has been controversial as a congressional investigation found last week that the FDA’s “atypical cooperation” in approving the expensive drug was “rife with irregularities.”
Before Aduhelm, the FDA had not approved a new therapy for the condition since 2003.
Aduhelm’s FDA approval and initial high price tag hit Medicare Part B premiums, increasing 2022 standard monthly payments by 14.5% to $170.10.
About $10 of the premium cap — or just under half the amount — was owed to Aduhelm, a CMS official told CNN in late 2021.
The premium increase was set before Medicare announced its limited coverage of the drug, but actuaries had to ensure the program had adequate funding in case Aduhelm was covered.
Medicare’s decision, as well as Biogen’s cut in the drug’s price, led to a decrease in monthly premiums for 2023 to $164.90.
The FDA’s accelerated approval of lecanemab was expected, said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic in the Center for Brain Health at Florida Atlantic University’s Schmidt College of Medicine.
Isaacson said lecanemab could be “another tool” in his toolbox to fight Alzheimer’s disease.
“I would prescribe this drug to the right person, at the right dose and in a very carefully monitored way, but this drug is not for everyone,” he said.
“I would do genetic testing for APOE4 first. I would have an honest discussion with my patients,” he said. and they must seek medical attention immediately.”
