He Food and Drug Administration on Thursday fully approved the Alzheimer’s drug Leqembi, amid concerns about its safety, cost and accessibility.
The move marks the first time that a drug intended to slow the progression of the disease has gained full regulatory approval. Other approved drugs only target your symptoms.
“I don’t think we can underestimate the importance of this moment,” said Donna Wilcock, associate dean for biomedicine at the University of Kentucky.
About 6.7 million adults 65 and older in the United States have Alzheimer’s disease, according to the Alzheimer’s Association.
Leqembi, from Japanese drugmaker Eisai and US-based drugmaker Biogen, targets a type of protein in the brain called beta-amyloid, which scientists have long thought was one cause. underlying Alzheimer’s disease.
in a phase 3 clinical trial of 1,795 patients with mild cognitive impairment or early-stage disease, disease progression slowed by 27% over an 18-month period.
“Although patients are still declining on the drug, the decline is slowing down,” Wilcock said.
Dr. Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minnesota, said in an email that Leqembi does not cure or stop the disease.
“It’s a first step for hopefully more therapies in the future,” he said.
The Alzheimer’s Association, which has openly advocated for the drug’s approval, praised the decision.
The treatment could “give people in the early stages of Alzheimer’s disease more time to maintain their independence and do the things they love,” Joanne Pike, president and CEO of the Alzheimer’s Association, said in a statement.
“This gives people more months to acknowledge their spouse, children and grandchildren,” Pike said.
How does Leqembi help Alzheimer’s patients?
In the phase 3 clinical trial, researchers measured cognitive decline using a scale which focused on patients’ performance in six categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
For each category, patients were rated on a 5-point scale: 0 is normal, 0.5 is questionable dementia, and 1, 2, and 3 are mild, moderate, and severe stages of dementia, respectively.
Patients in the placebo group scored, on average, 1.66 on the scale after 18 months. Those who scored Leqembi scored, on average, 1.21, a difference of 0.45, or a 27% slower rate of decline.
“In real world terms, this probably means more time for the patient to live independently, enjoy hobbies, friends and have a better quality of life,” Wilcock said. “Time will tell, but the clinical trial showed a significant benefit on measures of activities of daily living.”
Petersen said the drug appeared to slow the patient’s decline for about five months.
Others, however, were less optimistic about Leqembi’s benefits.
Dr. Alberto Espay, a neurologist at the University of Cincinnati School of Medicine, said the 27% slowdown in disease progression is below the threshold of what would be “noticeable” to a patient.
“The odds of brain swelling and bleeding are much higher than any real improvement,” said Espay, who launched a petition in June calling for the Alzheimer’s treatment not to gain full approval.
About 12.6% of patients who received Leqembi at trial developed brain swelling, compared with 1.7% of those in the placebo group. About 17% of the Leqembi group experienced brain bleeds, compared with 9% of the placebo group. The side effect is also seen with another Alzheimer’s drug, Biogen’s Aduhelm, which also works by targeting amyloid in the brain.
Three deaths were also linked to the drug in clinical trials.
Petersen said that in about 75% of people, the brain side effects, which were detected on MRIs, did not cause symptoms.
“However, the potential of these results needs to be discussed with patients,” he said. “Unusually, they can lead to big concerns.”
Who will be able to get Leqembi?
Leqembi was approved for people with mild cognitive impairment or early-stage Alzheimer’s disease.
The drug is administered intravenously every two weeks, which means patients will need to go to a hospital or clinic for the infusion.
In addition, a round table of Alzheimer’s experts recommends patients receive periodic brain scans to monitor for any side effects.
Leqembi will have a list price of $26,500 a year.
In June, the Centers for Medicare & Medicaid Services said it planned to provide coverage for Leqembi and other drugs in its class, subject to receiving full FDA approval. However, the agency said it will require doctors to collect real-world performance data on these drugs through a government database. That means that only doctors who are willing to collect this data will be able to prescribe Leqembi.
Tomas Philipson, an economist who served as chief economic adviser to the FDA and CMS under former President George W. Bush, said the rule means some patients still won’t be able to pay for Leqembi.
“It will limit a little bit, but not as much as what CMS is doing to the whole class right now,” Philipson said, referring to the restrictions the agency placed on drugs that had been granted accelerated approval, also known as as expedited approval. To receive coverage for accelerated approval drugs, patients must be enrolled in a clinical trial.
Leqembi initially received accelerated approval in January, before the FDA had time to review the results of the Phase 3 clinical trials.
In June, an independent advisory committee to the FDA voted unanimously that trial data showed that Leqembi provided benefit to Alzheimer’s patients, recommending that the agency should grant it full approval.
Leqembi’s approval is important for patients and the health care system, said Philipson, now a professor at the University of Chicago’s Harris School of Public Policy. co-authored a paper in June that it found that delaying coverage of Leqembi and other drugs in its class could cost the US more than $500 billion.
Leqembi’s full approval surpassed that of Biogen’s Aduhelm, which was granted accelerated approval in 2021.
That approval came despite a finding by an FDA advisory committee that the drug was unlikely to work. Later, a 18-month congressional investigation found that the FDA failed to meet its own standards and that its approval of Aduhelm was “full of irregularities,” putting the agency under further scrutiny.
Aduhelm initially cost $56,000 a year, threatening to increase Medicare premiums, before the company decided to Cut that total in half. With only expedited approval, the drug is only covered by Medicare if people are enrolled in a clinical trial.
No date has been set for when the FDA might make a decision on full approval of Aduhelm.
