The FDA approved a new Alzheimer's drug that may modestly slow the pace of cognitive decline early in the disease, but also carries risks of swelling and bleeding in the brain.
Patients and physicians are likely to be interested in the approval of lecanemab. Studies show that the drug is more promising than other treatments. Several Alzheimer's experts said it was not certain if Leqembi could slow cognitive decline enough to be noticed by patients.
A recent report of findings from a large 18-month clinical trial, published in the New England Journal of Medicine and co-written by scientists from the lead company making the drug, concluded that more trials are needed to determine the efficacy and safety of lecanemab.
The drug was developed and tested by Eisai. The companies will split the profits equally for the commercialization and marketing of the drug.
The list price is $26,500 per year. The price is higher than some analysts recommend.
The Institute for Clinical and Economic Review is an independent nonprofit organization that assesses the value of medicines. The institute said in a report last month that it would be cost-effective for patients to pay between $8,500 and $20,000 a year.
The large number of patients with Alzheimer's disease necessitates that new therapies be priced in line with their value to patients.
The F.D.A. council of senior officials said there was not enough evidence to support the approval of Aduhelm.
The approval process for Aduhelm was found to berife with irregularity and involved a close collaboration with Biogen. According to the F.D.A., the agency has begun implementing changes in line with the committees recommendations.
An F.D.A. official said that there were many important lessons learned after the approval of Aduhelm.
A drug that is not proven to work. The F.D.A.'s independent advisory committee and a council of senior agency officials voted that there was no proof that Aduhelm slowed cognitive decline. The agency approved the drug even though it wasn't perfect. It required Biogen, the drug's manufacturer, to conduct a new clinical trial but gave them more than eight years to complete it.
Concerns are growing. There were questions about the approval and whether the F.D.A. worked too closely with Biogen. The Cleveland Clinic and the Department of Veterans Affairs didn't offer Aduhelm.
The F.D.A. changed the language on the drug label with Leqembi. The Aduhelm label was changed one month after it was approved.
Leqembi should only be used for patients in early and mild stages of Alzheimer's disease, according to the label. One of the hallmarks of Alzheimer's is a build up of the amyloid in the brain.
In the case of Leqembi, more detail and clarity on the most appropriate patient population for use of the drug, and greater explanation around safety have been added to the label.
The official said that the F.D.A. worked with the companies to include more diversity in the clinical trials. 25 percent of the United States participants in the Leqembi trials were black or Hispanic.
Ivan Cheung, the chairman and chief executive of Eisai's United States operations, said in an interview that they worked very hard with the F.D.A. to narrow down who should be eligible for the treatment.
About 1.5 million of the six million people with Alzheimer's in the United States are thought to be in the beginning stages of the disease. If Medicare doesn't cover the drug, how many will be treated?
The Centers for Medicare and Medicaid Services limited Medicare coverage for Aduhelm last year due to the treatment's unclear benefit and safety risks. The price of Aduhelm made it hard for many patients to afford it.
If the agency determines that Leqembi has better evidence of helping patients, Medicare can cover it for all eligible patients and only impose a requirement that the patients experience be tracked.
The warnings about brain swelling and brain bleeding are similar to those of Aduhelm.
Cautionary language about taking blood thinners while on the treatment was not addressed on Aduhelm's label. The label warns against giving blood thinners to a Leqembi patient.
The deaths of three patients who experienced brain swelling and brain bleeding, two of which were being treated with blood thinners, have raised concerns about safety. Patients in a large Phase 3 trial of the drug were not told if they received it or not. They died after being treated with lecanemab in an open label extension study.
The subject of a report this week in the New England Journal of Medicine was a 65-year-old woman who had a stroke and died after receiving a standard treatment for blood clot problems. In an earlier article about the case in the journal Science, a neuropathologist said he believed that Leqembi weakened her blood vessels and made them vulnerable to bursting when she received the blood clot treatment.
Two researchers involved in the Leqembi trial wrote a letter to the New England Journal of Medicine stating that t- PA appears to be the cause of death, not Leqembi. The case raises important issues for patients with Alzheimer's disease.
The brand name was greenlighted on Friday under a designation called "accelrated approval." The F.D.A. is able to give accelerated approval to drugs if they are for serious diseases with few treatments and attack a biological part of the disease.
Many Alzheimer's experts said years of data had not shown that reducing amyloid slowed cognitive decline, which caused Aduhelm to be controversial.
Many experts don't believe that attacking amyloid can benefit Alzheimer's patients. The data is more consistent than Aduhelm and may be related to the fact that Leqembi targets a different type of amyloid.
In recent months data from a large Phase 3 trial has supported the earlier results and provided more information. Patients receiving Leqembi declined more slowly over 18 months than patients receiving a placebo, on an 18-point cognitive scale that assessed functions like memory and problem-solving. Patients on placebo declined by 1.66 points. It's a 27 percent slower decline.
Data on biological markers was stronger for Leqembi than for a placebo, and the patients declined more slowly on three measures of cognitive function.
An experimental treatment targeting brain amyloid in Alzheimer's disease appears to slow cognitive decline.
The difference between lecanemab and placebo is not considered to be a clinically meaningful treatment effect.
Less than 2 percent of patients receiving the placebo experienced brain swelling, which was mild or moderate, in the Phase 3 trial. Within a few months, most brain swelling did not cause any problems. 17 percent of Leqembi patients had brain bleeding, compared with 9 percent of placebo patients. dizziness was the most common symptom.
Fourteen percent of Leqembi patients and eleven percent of placebo recipients had serious adverse events, according to the authors. More than twice as many Leqembi patients dropped out of the trial because of negative side effects as placebo recipients.
The risk of brain bleeding and swelling was lower in the trials of Aduhelm.
Before full approval can be considered, another clinical trial of a drug must be conducted. The Phase 3 trial results will be used to apply for full approval.
It's not clear if Medicare will cover Leqembi while it's approved. The decision to limit coverage of Aduhelm technically applies to Leqembi and other drugs in the same class of drugs, but the Medicare agency said that it would beimble and evaluate each new medication.
Health economists say that full approval of Leqembi would make Medicare coverage more likely.
Mr. Cheung wanted to lower expectations about how many patients would be prescribed Leqembi and how quickly they would use it. He said that even if Medicare doesn't cover the drug in three years, there could be 100,000 people who use it.
There are a lot of unanswered questions about the drug. Some data about the drug suggests that it can accelerate brain shrinkage, which should be investigated because it could be a sign that the disease is getting worse. There is a question about whether patients with cerebral amyloid angiopathy should use Leqembi.
Since C.A.A. is ubiquitous in Alzheimer's, it made sense to allow patients to use Leqembi with appropriate monitoring.
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