Food and Drug Administration on Thursday It gave full approval to the drug Leqembi for the treatment of Alzheimer’s diseaseMedicare said it would cover much of its prohibitive cost, laying the groundwork for widespread use of drugs that can slightly slow cognitive decline in the early stages of the disease but also carry significant safety risks.
The FDA’s decision marks the first time in two decades that a drug for Alzheimer’s disease has received full approval, meaning the agency concluded there was strong evidence of potential benefit. But the agency has also added a so-called black box warning — the most urgent level — on the Medication labelnoting that in rare cases the drug can cause “serious and life-threatening events” and that there have been cases of cerebral hemorrhage, “some of which have been fatal”.
Leqembi cannot repair cognitive damage, reverse the disease, or prevent it from getting worse. But data from a large clinical trial suggests the drug — given every two weeks as an intravenous infusion — may slow the decline by about five months over about 18 months for people with mild symptoms.
However, some Alzheimer’s experts said it is It is not clear from the medical evidence Whether Leqembi’s ability to delay the erosion of memory and cognition is sufficient to be noticeable and meaningful to patients and their families remains to be seen. And while most cases of brain swelling and hemorrhage were mild or moderate and resolved, there were some serious cases.
“The risks are very clear,” said Dr. Jason Karlawich, co-director of the Penn Memory Center at the University of Pennsylvania, who said he would prescribe Leqembi after carefully evaluating patients and explaining the potential pros and cons. “Within the first few months, you may have minor bleeding or swelling in your brain, which may or may not be asymptomatic and if not caught in time can cause disability.”
Dr. Karlawich continued, “By contrast, the benefits of deceleration are subtle. You will not experience perceiving changes in your cognition or function at the same time.”
Although Medicare will cover 80 percent of Leqembi’s $26,500 cost, patients can still afford thousands of dollars in co-payments.
Japanese pharmaceutical company Eisai led the development and testing of Leqembi (pronounced le-KEM-bee). Eisai is partnering and splitting profits with the US company Biogen, the manufacturer of the controversial Alzheimer’s drug Aduhelm, to market and market it.
The Food and Drug Administration’s approval of Aduhelm has been heavily criticized because the evidence of potential benefit has been inconclusive, with one trial showing a modest slowing of remission while another no. Prior to this approval, a panel of independent advisors and a board of senior FDA officials had said there was insufficient evidence that it worked. Many medical centers refused to prescribe Aduhelm, and Medicare only covered it for clinical trial participants, severely limiting its availability.
Alzheimer’s experts said the evidence supporting Leqembi is clearer.
Leqembi will be available to people with mild dementia or a pre-Alzheimer’s condition called mild cognitive impairment. The FDA poster instructs doctors not to treat patients without testing to ensure they have a buildup of the protein amyloid, the hallmark of Alzheimer’s disease that Lekembe attacks.
It is estimated that about 1.5 million people in the United States are in the early stages of Alzheimer’s disease. Much more – about five million – have progressed far short of qualifying for Leqembi. Alex Scott, Eisai’s executive vice president of integrity, said the company recommends that patients stop using Leqembi as soon as they develop mild Alzheimer’s disease.
Alzheimer’s experts said they will report to some patients that they are at higher risk for brain swelling and bleeding — including those who take blood thinners, those with more than four microscopic hemorrhages in the brain and those who have an Alzheimer’s disease-related gene mutation called APOE4.
The risk for people with two copies of the APOE4 mutation — about 15 percent of people with Alzheimer’s disease — is so high that the FDA’s black box warning recommends genetic testing of all patients to assess their safety risks and states that those with two APOE4s are Copies are more likely to have “symptomatic, serious and acute” hemorrhage or swelling of the brain.
The black box warning will apply to all drugs that, like Leqembi, are monoclonal antibodies that attack amyloid. Leqembi is the first to receive full approval, but others are in various stages of development.
The warning did not mention patients taking blood thinners, but Leqembi’s label states that “extra caution should be exercised” when considering whether blood thinners should be given to Leqembi patients.
The FDA has given the green light to Aduhelm under a program called “expedited approval,” which can be given to drugs with uncertain benefits subject to specific criteria, including that the company conduct another clinical trial. Leqembi received fast-track approval in January, but that status means Medicare will only cover the drug in limited circumstances.
The FDA’s decision to grant full approval to Leqembi means Medicare will cover it for eligible patients.
However, some patients won’t be able to afford the 20 percent that Medicare doesn’t cover, probably about $6,600 a year. Including the costs of required medical visits and regular brain scans, some of which will receive Medicare reimbursement, treatment can amount to about $90,000 per yearSome experts estimate.
A recent study He estimated that covering essential drugs and services for about 85,000 patients would cost Medicare $2 billion annually and would rise to $5.1 billion if the number of patients reached about 216,000. This could lead to higher insurance premiums for all Medicare beneficiaries, not just those receiving Leqembi, the study said.
In interviews, Evan Cheung, president and CEO of Esay’s U.S. operations, estimated that in the first three years, about 100,000 patients would receive the drug.
Medicare adds a requirement Doctors prescribing Leqembi provide medical information around each patient before and during their treatment with the drug. The agency said the information will be kept in patient records and evaluated to learn more about Leqembi’s benefits or harms.
“With the FDA’s decision, CMS will cover this drug broadly while continuing to collect data that will help us understand how the drug works,” said Chiquita Brooks-LaSure, director of the Centers for Medicare and Medicaid Services, in a statement.
Some advocacy groups, such as the Alzheimer’s Association, have Swipe for registration requirementsdescribing it as an unnecessary hindrance to access. But medical experts say registration programs are popular and easy to comply with. Their concern is that the registry will not compare Leqembi patients with others, so it will not be able to say whether Leqembi is slowing cognitive decline.
Thursday’s US Food and Drug Administration (FDA) approval was based on a large trial indicating that patients receiving Leqembi dropped 27 percent more slowly over 18 months than patients receiving a placebo. The difference between those receiving the drug and the placebo was small — less than half a point, on an 18-point cognitive scale that assesses functions such as memory and problem-solving. Some Alzheimer’s experts say that for a slowing of decline to be clinically meaningful, or noticeable to patients and families, the difference between groups must be at least one point.
Leqembi patients also declined more slowly on three secondary measures of cognition and daily function, and data on biomarkers were generally stronger for Leqembi than for placebo. All of these measures moving in the same direction, experts say, reinforce the idea that the drug can benefit patients.
Still, report on the data, published In the New England Journal of Medicine and co-written by scientists from Eisai, they conclude that “Longer trials are warranted to determine efficacy and safety.”
Reports have raised safety concerns Death cases Of the three clinical trial participants who experienced brain swelling and bleeding in the brain, two were being treated with blood thinners. It’s unclear if Leqembi contributed to their deaths, Isai said, because the patients had complex medical problems.
“You have small benefits and certain risks of serious adverse events, and that has to be balanced,” said Dr. Lon Schneider, director of the California Center for Alzheimer’s Disease at USC, who said he would prescribe Leqembi. To evaluate patients carefully.
“If it had been more effective,” he said, “we wouldn’t be talking about negative events as much as we would see a clear benefit,” adding, “I think a lot of people will see this and say it’s not worth the effort, it’s not worth twice a month.”
d said. Karlawish said the decisions facing patients and their families will be complex. Because eligible patients have only mild symptoms of cognitive decline, some may choose to take any drug that may prolong that functional phase relatively, while others may only consider the meaningful drug risks if they are more debilitated.
One recent patient refused to get an evaluation of a potential treatment, Dr. Karlawich said, stating, “I want more benefits, I don’t see the value.” But he said, “I have other patients, though, who’s to say, ‘You mean you can give me a drug that can slow down the disease?'”
In the trial, approximately 13 percent of patients given Leqembi experienced brain swelling, which was mostly mild or moderate, while less than 2 percent of patients receiving placebo experienced such swelling. Most cases of brain swelling do not cause any symptoms, usually appearing soon after starting use and resolving within a few months. About 17 percent of Leqembi’s patients experienced bleeding in the brain, compared to 9 percent of patients given a placebo. The most common symptom of a brain hemorrhage is dizziness.
Overall, the results indicate that the risk of brain bleeding and swelling was significantly lower than in patients in the Aduhelm trials.
Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who studies drug regulation and use, said doctors will feel pressure to prescribe the drug to my patients, families and advocacy organizations. He said medical institutions would also have a “tremendous financial incentive” because of the Medicare reimbursement that “they can then spend on social workers and all the other things that Medicare won’t reimburse,” he said, adding that “any self-respecting memory center that’s economical is going to see this on.” It is an economic windfall.”