Food and Drug Administration on Thursday Alzheimer’s drug Lekembi gets full approvalAnd Medicare said it would cover its high cost, laying the foundation for widespread use of a drug that may slow cognitive decline in the early stages of the disease but also carries significant safety risks.
The FDA’s decision is the first time in two decades that an Alzheimer’s drug has received full approval, meaning the agency has concluded there is strong evidence of potential benefit. But the agency also added a so-called black-box warning – the most critical level. medicine labelStating that in rare cases the drug can cause “serious and life-threatening events” and that cases of cerebral hemorrhage have also been reported, “some of which have been fatal.”
Lekembi cannot repair cognitive damage, reverse the course of the disease, or stop it from getting worse. But data from a large clinical trial suggests that the drug – which is given as an intravenous infusion every two weeks – may slow the progression from about five months to about 18 months for people with mild symptoms. Is.
Nevertheless, some Alzheimer’s experts have said that it is unclear from medical evidence Whether Lecambi’s ability to delay the decline of memory and cognition will be enough to be noticeable or meaningful to patients and their families remains to be seen. And while most cases of swelling and bleeding in the brain were mild or moderate and have recovered, there have been some severe cases.
“The risks are very clear,” said Dr. Jason Karlwisch, co-director of the Penn Memory Center at the University of Pennsylvania, who said he would prescribe Lekembi after carefully evaluating patients and explaining the potential pros and cons. “Within the first few months, you may have small bleeding or swelling in the brain, which may or may not have symptoms and can lead to disability if not detected in time.”
“In contrast,” Dr. Karlavish continued, “the benefits of slow motion are subtle. You won’t experience a change in your cognition or functioning at the same time.”
Although Medicare will cover 80 percent of LeCamby’s $26,500 cost, patients can still bear thousands of dollars in co-pays.
The Japanese pharmaceutical company Eisai led the development and testing of Lekembi (pronounced lay-KEM-bee). Christiani is partnering with American company Biogen, the maker of the controversial Alzheimer’s drug EduHelm, for its commercialization and marketing and is sharing the profits.
The FDA approval of EduHelm was strongly criticized because the evidence for potential benefit was inconclusive, with one trial showing a slight slowing of degradation but another trial showing no slowing. Prior to that approval, a committee of independent advisers and an FDA council of senior officials said there was not enough evidence that it works. Many medical centers refused to prescribe EduHelm, and Medicare covered it only for clinical trial participants, sharply limiting its availability.
Alzheimer’s experts said the evidence supporting Lekembi is more clear.
Lekembi will be available to people with a pre-Alzheimer’s condition called mild dementia or mild cognitive impairment. The FDA label instructs doctors not to treat patients without testing to confirm they have accumulations of the protein amyloid, a hallmark of Alzheimer’s, which Lekembi attacks.
It is estimated that about 1.5 million people in the United States have early stages of Alzheimer’s. Many more – around five million – have advanced too far to be eligible for Lekembi. Alex Scott, executive vice president of Integrity for Eisai, said the company advises patients to stop using Lekembi if they develop moderate Alzheimer’s disease.
Alzheimer’s experts said they will inform some patients they have a higher risk of swelling and bleeding in the brain — including those taking blood-thinning drugs, those with more than four microhemorrhages in the brain and those with an Alzheimer’s-associated gene mutation called APOE4. people are involved.
The risk for people with two copies of the APOE4 mutation — about 15 percent of people with Alzheimer’s — is so high that the FDA’s black-box warning recommends that all patients be genetically tested to assess their safety risk. be done and people with two APOE4 are detected. Copies are more vulnerable to developing “symptomatic, severe and severe” cerebral hemorrhage or swelling.
The black-box warning would apply to all drugs that, like Lekembi, are monoclonal antibodies that attack amyloid. Lekembi is the first to receive full approval, but others are in various stages of development.
The warning does not mention patients who are taking blood thinners, but Lekembi’s label states that when considering whether to give Lekembi patients with blood thinners “additional Caution should be taken”.
The FDA gave the green light to EduHelm under a program called “accelerated approval,” which allows drugs of uncertain benefit to be granted under specific criteria, including the company conducting another clinical trial. Lekembi received accelerated approval in January, but that status meant that Medicare would cover the drug only under limited circumstances.
The FDA’s decision to grant Lekembi full approval means that Medicare will cover it for eligible patients.
Even so, some patients will be unable to cover the 20 percent Medicare covers, potentially around $6,600 per year. Including the cost of medical visits and necessary routine brain scans, some of which will receive Medicare reimbursement, treatment can run approx. $90,000 per yearSome experts speculate.
recent study Medicare is estimated to cost $2 billion a year, rising to $5.1 billion if drugs and essential services are covered for about 85,000 patients. If the number of patients reached around 216,000. This could lead to premium increases for all Medicare beneficiaries, not just those receiving Lekambi, the study said.
In the interview, Evan Cheung, president and chief executive of Eisai’s United States operations, estimated that in the first three years, about 100,000 patients would receive the drug.
Medicare agency adding a requirement The doctor who prescribes Lekembi presents medical information About each patient before and during drug treatment. The agency said the information will be kept in patient registries and further evaluated to learn more about the benefits or harms of Lekembi.
In a statement, Chiquita Brooks-Lasur, administrator of the Centers for Medicare and Medicaid Services, said, “With the FDA’s decision, CMS will cover this drug more broadly, collecting data that will help us better understand how the drug works.” Works.”
Some advocacy groups, such as the Alzheimer’s Association, have done Registry requirement criticizedThis is being termed as an unnecessary barrier to access. But medical experts say registry programs are common and easy to follow. Their concern is that the registry will not compare Lekembi patients with others, so it won’t be able to say whether Lekembi slows cognitive decline.
The FDA’s approval on Thursday was based on a large trial that showed patients receiving Lekembi declined 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 on an 18-point cognitive scale, which assesses functions such as memory and problem-solving. Some Alzheimer’s experts say that for the slowing of decline to be clinically meaningful, or noticeable to patients and families, the difference between the groups must be at least one point.
Three secondary measures of cognition and daily functioning also declined more slowly in Lekembi patients, and data on biological markers were generally stronger for Lekembi than for placebo. Experts say all these measures move in the same direction, reinforcing the idea that the drug can benefit patients.
Nevertheless, a report on the data, published The study, in The New England Journal of Medicine and co-authored by Issai scientists, concluded that “longer trials are needed to determine efficacy and safety.”
Reports have raised concerns about security deaths Of the three clinical trial participants who experienced brain swelling and brain hemorrhage, two were being treated with blood-thinning drugs. Isai has said it is unclear whether Lekembi contributed to their deaths because the patients had complex medical problems.
“You’ve got a small benefit and a definite risk for serious adverse events, and that has to be balanced,” said Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California. Patients were carefully assessed.
“If its efficacy was greater, we wouldn’t talk as much about adverse events because we would see a clear benefit,” he said. He said, “I think many people will look at it and say it’s not worth the effort, it’s not worth it.” Infusion twice a month.”
Dr. Karlavish said the decisions facing patients and families will be complex. Because eligible patients have only mild symptoms of cognitive decline, some may choose to take any drug that can prolong that relatively functional phase, while others may consider the risks of the drug to be worthwhile only if they Be too weak
Dr. Karlavish noted that a patient recently declined to be evaluated for a potential treatment, indicating “‘I want more benefit, I don’t see the value.'” But, he added, “my There are other patients too, though, who’s to say, you mean you can give me a drug that can slow down the disease?
In the trial, about 13 percent of patients receiving Lekambi experienced brain swelling, which was mostly mild or moderate, while less than 2 percent of patients receiving a placebo experienced such swelling. Most sprains cause no symptoms, usually appear soon after use begins and resolve within a few months. About 17 percent of Lekembi patients experienced brain bleeding, compared to 9 percent of patients who received a placebo. The most common symptom of cerebral hemorrhage was dizziness.
Overall, the results suggest that the risk of bleeding and swelling in the brain was significantly lower than in patients in the trials for EduHelm.
Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who studies drug regulation and use, said doctors will feel pressure to prescribe Lekembi from patients, families and advocacy organizations. Medicare reimbursement would also give medical institutions a “huge financial incentive” that “then they can spend on social workers and everything else that Medicare won’t reimburse,” he said, adding that “no financially self-respecting memory The Center will see this as an economic windfall.”