Alzheimer’s drug lecanemab receives accelerated FDA approval amid safety concerns


The U.S. Food and Drug Administration granted accelerated approval Friday for the Alzheimer’s disease drug lecanemab, one of the first experimental dementia drugs that appears to slow the progression of cognitive decline.

Director of the Office of Neurology at the FDA’s Center for Drug Evaluation and Research, Dr. “Alzheimer’s disease immeasurably impairs the lives of its sufferers and has a devastating impact on their loved ones,” said Billy Dunn. “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 Legembi, the FDA said in a statement. A Phase 3 trial showed “potential” as a treatment for Alzheimer’s disease, showing slow progress, but raised safety concerns due to its association with certain serious adverse events, including brain swelling and bleeding.

In July, the FDA accepted Eisai’s Biologics License Application for lecanemab through accelerated approval, giving the drug priority review, according to the company. The accelerated approval program allows 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 trials.

If these trials confirm that the drug provides clinical benefit, the FDA may grant conventional approval. But if a confirmatory trial doesn’t show benefit, the FDA has regulatory procedures that can lead to taking a drug off the market.

Lecanemab, a monoclonal antibody, is not curative, but works by binding to amyloid beta, a hallmark of Alzheimer’s disease. Results of an 18-month Phase 3 clinical trial published in The New England Journal of Medicine in late November showed that lecanemab “reduced amyloid markers in early Alzheimer’s disease and resulted in moderately less decline in measures of cognition and function than placebo at 18 months, but was associated with adverse events.

The results also showed that approximately 6.9% of trial participants receiving lecanemab as an intravenous infusion discontinued the trial due to adverse events, compared with 2.9% of those receiving placebo. Overall, serious adverse events occurred in 14% of the lecanemab group and 11.3% of the placebo group.

The most common adverse events in the lecanemab group were reactions to intravenous infusions and abnormalities on their MRIs, such as brain swelling, called amyloid-related imaging abnormalities, and bleeding or ARIA, which can be life-threatening.

Some people who receive ARIA may not have symptoms, but it can sometimes lead to hospitalization or long-term impairment. People with a gene called APOE4, which can increase the risk of Alzheimer’s disease or other dementias, appear to have a higher incidence of ARIA. The study found that ARIA was “numerically less prevalent” among non-APOE4 carriers.

The FDA says the drug’s prescribing information warns about ARIA.

The trial results also showed that about 0.7% of participants in the lecanemab group and 0.8% of those in the placebo group died, compared to six deaths in the lecanemab group and seven in the placebo group.

The Alzheimer’s Association welcomed Friday’s decision.

“When caught in the early stages of Alzheimer’s, by slowing the progression of the disease, individuals will have more time to participate in daily life and live independently,” said Joanne Pike, President and CEO. “It could mean more months to get to know your spouse, children and grandchildren. It also means more time for a person to drive safely, accurately and promptly, take care of family finances, and fully participate in their hobbies and interests.”

According to the Alzheimer’s Association, more than 6.5 million people in the United States are living with Alzheimer’s disease, and that number is expected to reach 13.8 million by 2060.

Lecanemab will carry a wholesale price of $26,500 per patient per year, the drugmakers announced Friday.

Biogen and Eisai listed the drug just below the low price of Alzheimer’s drug Aduhelm, which now costs about $28,200 for the average patient. After insurers refused to pay for it, the companies had to lower the cost of Aduhelm – originally set at $ 56,000 per patient per year.

Basing Legembi’s cost, the companies said in a news release that the drug’s cost to society is about $37,000 a year, based on the estimated quality of life achieved by people taking it, but chose to go lower. promoting greater access to patients, reducing the overall financial burden and supporting health system sustainability.

The wholesale price of a drug is like the sticker price of a car. It’s not necessarily what patients will pay after insurance or other discounts are taken into account.

However, this drug is not covered by insurance. 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 drugs.

Centers for Medicare and Medicaid Services Administrator Chiquita Brooks-LaSure said after the FDA’s decision Friday that her office will quickly review Legembi, but for now, it will be covered in the same way as Aduhelm because of its accelerated approval.

“At CMS, we will continue to proactively review data on these products as they become available, and we are committed to timely access to treatments, including drugs that improve clinically meaningful outcomes,” Brooks-LaSure said.

Last month, the Alzheimer’s Association filed a formal request asking CMS to provide “full and unrestricted coverage” of FDA-approved Alzheimer’s treatments.

“What the FDA did today by granting accelerated approval to Legembi was the right decision. But what CMS has done by severely limiting coverage for approved treatments is unprecedented and wrong,” Pike said in a statement Friday.

“The FDA carefully reviewed the evidence for Legembi before granting approval. CMS, in stark contrast, denied coverage for Legembi months before reviewing the evidence for this drug. CMS has never done this for any drug before, and it is clearly harmful and unfair to those with Alzheimer’s. Without access to and coverage for this treatment and others in its class, people spend days, weeks, months – losing memories, skills and independence. They are wasting time.”

CMS told CNN it will review and respond to the association’s request. The agency also noted that it continues to be aware of ongoing clinical trials, including the latest lecanemab results published in the New England Journal of Medicine. Also, met with drug manufacturers to learn about their efforts after the CMS coverage decision was announced.

The FDA approved Aduhelm for the early stages of Alzheimer’s disease in 2021 — but the decision has been mired in controversy since last week a congressional investigation found the FDA’s “atypical cooperation” to approve the high-priced drug was “rife with irregularities.”

Before Aduhelm, the FDA had not approved a new treatment for the condition since 2003.

Aduhelm’s FDA approval and initial high price tag hit Medicare Part B premiums, raising standard monthly payments by 14.5% to $170.10 for 2022.

A CMS official told CNN in late 2021 that about $10 of the premium increase, or less than half of the amount, was due to Aduhelm.

The premium increase was set before Medicare announced limited coverage of the drug, but its actuaries had to make sure the program was sufficiently funded if Aduhelm was covered.

Medicare’s decision, as well as Biogen’s reduction in the price of the drug, caused monthly premiums to drop to $164.90 for 2023.

Director of the Alzheimer’s Prevention Clinic at the Center for Brain Health at Florida Atlantic University Schmidt College of Medicine, Dr. Richard Isaacson said the FDA expects accelerated approval of lecanemab.

Isaacson said lecanemab could be “another tool” in the toolbox to fight Alzheimer’s disease.

“I will prescribe this drug to the right person, at the right dose and very carefully monitored, but this drug is not for everyone,” he said.

“I would do genetic testing for APOE4 first. I would have a frank conversation with my patients,” he said. “If someone has side effects, if someone is on blood thinners, if someone has a problem, they should discuss it with their treating physician and seek immediate medical attention.”

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