Food and Drug Administration on Thursday Full approval of Alzheimer’s disease drug Rekumbiand Medicare said it lays the groundwork for widespread use of drugs that cover many of the high costs and can slow some cognitive decline in the early stages of the disease, but also carry significant safety risks. .
The FDA’s decision marks the first time in 20 years that a drug for Alzheimer’s disease has been fully approved and means the FDA has concluded that there is strong evidence of potential benefit. But the authorities also put the most urgent level of so-called black-box warnings, medicine labelsaid the drug could cause “serious and life-threatening events” in rare cases, including cerebral hemorrhages, “some of which were fatal.”
Rekembi cannot repair cognitive impairment, reverse the course of the disease, or stop its deterioration. But data from a large clinical trial suggest that the drug, given as an intravenous infusion every two weeks, could delay the decline by about five months, for about 18 months in people with mild symptoms. It is
Still, some Alzheimer’s experts say it does. Unknown from medical evidence Whether Rekembi’s ability to slow memory and cognitive erosion is noteworthy or meaningful for patients and their families. Also, while most cases of brain swelling and bleeding are mild or moderate and resolve, there are some severe cases.
“The risks are very clear,” said Jason Karawish, M.D., co-director of the Penn Memory Center at the University of Pennsylvania. Stated. “Within the first few months, there may be minor bleeding or swelling in the brain, which may or may not be symptomatic and can cause disability if not detected in time.”
“By contrast,” continued Dr. Karlawish. “The benefits of slowing down are subtle. You can’t experience cognitive or functional changes in the same amount of time.”
Medicare will cover 80% of Rekumbi’s $26,500 cost, but patients can still have thousands of dollars in out-of-pocket costs.
Japanese pharmaceutical company Eisai spearheaded the development and testing of Rekembi (pronounced Le Kem Bee). Eisai shares profits from a commercialization and marketing partnership with US company Biogen, maker of the controversial Alzheimer’s drug Aduhelm.
The FDA’s approval of Aduhelm was heavily criticized because evidence of a potential effect was inconclusive, with one trial showing a gradual slowing of decline but another showing no slowing. Prior to this approval, a panel of independent advisors and a council of senior FDA officials said there was not enough evidence that the drug worked. Many medical centers refuse to prescribe Aduhelm, and Medicare is only for clinical trial participants, severely limiting its availability.
Alzheimer’s experts say the evidence supporting Rekumbi is becoming clearer.
Leqembi will be available to people with a pre-Alzheimer’s disease condition called mild dementia or mild cognitive impairment. The FDA label tells doctors not to treat patients without testing to confirm that they have accumulated the protein amyloid that characterizes the Alzheimer’s disease that Lekemi attacks.
It is estimated that about 1.5 million people in the United States are in the early stages of Alzheimer’s disease. Many more people (about 5 million) are too advanced to qualify for Rekembi. Alex Scott, Eisai’s executive vice president of integrity, said the company recommends that patients stop using Rekembi once they develop moderate Alzheimer’s disease.
Alzheimer’s experts said they will tell some patients that they are at increased risk of brain swelling and bleeding. This includes patients taking anticoagulants, those with four or more microbleeds in the brain, and those with a genetic mutation associated with Alzheimer’s disease called APOE4.
The risk for people with two copies of the APOE4 mutation (approximately 15 percent of Alzheimer’s disease patients) is so high that the FDA’s black box warning urges all patients to undergo genetic testing to assess safety risk. and states that people with two APOE4 mutations are at risk. Copies are more vulnerable to ‘syndromic severe’ cerebral hemorrhage and cerebral swelling.
The black box warning applies to all drugs, like Lekhembi, that are monoclonal antibodies that attack amyloid. Leqembi was the first to receive full approval, but other products are in various stages of development.
Although the warning does not mention patients taking blood thinners, the Rekumbi label states, “Use extra caution when considering whether to give blood thinners to patients with Rekumbi.” should be paid.”
The FDA gave Aduhelm the go-ahead under a program called “accelerated approval,” which allows it to grant drugs with uncertain efficacy under certain criteria, including having the company conduct separate clinical trials. Lekembi received early approval in January, but its status meant Medicare only covered the drug in limited circumstances.
The FDA’s decision to grant full approval for Leqembi means Medicare will cover Leqembi for eligible patients.
Still, some patients won’t be able to pay the 20% that Medicare doesn’t cover, probably about $6,600 a year.If you include the cost of medical visits and the required regular brain scans, some of which will be reimbursed by Medicare, the treatment costs about $90,000 per yearSome experts estimate that
Recent research Covering medications and necessary services for about 85,000 patients, Medicare costs are estimated to be $2 billion annually, rising to $5.1 billion when the patient population reaches about 216,000. This could lead to higher premiums for all Medicare recipients, not just Rekumbi recipients, the study said.
About 100,000 patients will receive the drug in the first three years, Ivan Chang, chairman and chief executive of Eisai’s U.S. business, estimated in an interview.
Medicare Agencies Are Adding Requirements Physicians prescribing Lekhembi must provide medical information For each patient before and during drug treatment. The information will be stored in patient registries and evaluated to learn more about the benefits and harms of Rekumbi, officials said.
“The FDA’s decision will allow CMS to provide broader coverage for this drug while providing data that will help us understand how the drug works,” Chiquita Brooks Rashua, director of the Centers for Medicare and Medicaid Services, said in a statement. We will continue to collect,” he said.
Some advocacy groups, such as the Alzheimer’s Association, criticized registry requirements, calling it an unnecessary barrier to access. But medical experts say registration programs are common and easy to comply with. Their concern is that registries do not compare patients with Rekembi to other patients, so they cannot determine whether Rekembi slows cognitive decline.
Thursday’s FDA approval was based on a large trial that showed patients on Rekumbi experienced a 27% slower decline over 18 months than those on a placebo. The difference between the drug-treated and placebo-treated patients was small, less than 0.5 points on an 18-point cognitive scale that assesses functions such as memory and problem-solving. Some Alzheimer’s disease experts say the difference between groups must be at least 1 point for the slowing of decline to be clinically meaningful or noticeable to patients and families. .
Rekembi patients also experienced slower declines in three secondary measures of cognition and daily living functioning, and data on biological markers were generally stronger with Rekembi than with placebo. Experts say all these steps going in the same direction strengthen the idea that the drug could benefit patients.
Yet the report on the data published A paper published in the New England Journal of Medicine and co-authored by Eisai scientists concluded that “longer trials are needed to determine efficacy and safety.” increase.
Concerns about safety are heightened by reports of: fatalities (number) Three clinical trial participants experienced brain swelling and cerebral hemorrhage, two of whom were being treated with blood thinners. Eisai said it was unclear whether Rekembi contributed to the deaths because the patients had complicated medical problems.
“There’s a small benefit, but there’s a certain risk of serious adverse events,” said Ron Schneider, Ph.D., director of the University of Southern California California Alzheimer’s Center, who said he would prescribe Lekumbi. Evaluate the patient carefully.
“If it were more effective, there would be clear benefits, so there wouldn’t be much talk about adverse events,” he said. I would say no,” he added. It’s a drip twice a month. “
Karlawish said the decisions patients and families face will be complicated. Since targeted patients have only mild symptoms of cognitive decline, some may choose to take medications that may prolong the relatively functional phase, but are more impaired. Some may consider the risks of drugs only in severe cases.
Karlawish said one patient recently declined to be evaluated for potential treatments, saying, “I want more, but I don’t see the value.” “Does that mean you’ll give me medicine to slow the disease?”
In this trial, nearly 13 percent of patients who received Rekumbi experienced brain swelling, most of which was mild or moderate, whereas no patients who received placebo experienced such swelling. was less than 2 percent. Most brain swelling did not cause any symptoms, usually appeared soon after starting use and resolved within a few months. About 17 percent of Lekembi patients experienced a cerebral hemorrhage, compared with 9 percent of those who received placebo. The most common symptom of cerebral hemorrhage was dizziness.
Overall, the results suggest that the risk of cerebral hemorrhage and swelling was significantly lower than in patients in the Aduhelm clinical trial.
Dr. Jerry Avon, a Harvard Medical School professor of medicine who studies drug regulation and use, said doctors would feel pressure from patients, families and advocacy groups to prescribe Lekembi. He also said that Medicare reimbursement provides “tremendous financial incentives” for health care providers and “allows health care providers to spend on social workers and all other costs that Medicare does not reimburse.” Any self-respecting memory center would consider this an economic windfall.”
