The Alzheimer’s drug Leqembi is seen in this undated image obtained by Reuters on January 20, 2023.
Eisai | via Reuters
A panel of independent advisers to the Food and Drug Administration on Friday unanimously approved the Alzheimer’s drug Leqembi, made by Eisai and Biogenpaving the way for full treatment approval this summer.
The councilors voted 6-0 that Eisai’s data showed clinical benefit for patients. The FDA is not required to follow the advisers’ recommendation, but the panel’s vote for Leqembi will weigh heavily in favor of full approval.
The FDA is expected to make a final decision on Leqembi on July 6. The agency’s decision will determine whether Medicare broadly covers the treatment. The adult program severely limits Leqembi’s coverage at this time, as it was previously approved through an expedited process.
Eisai has set Leqembi’s annual list price at $26,500 per year, meaning most patients cannot afford the treatment without Medicare coverage.
The Leqembi Advisory Committee on Friday was unusually small, with only six voting members.
Dr. Teresa Buracchio, acting head of the FDA’s office of neuroscience, said the smaller-than-usual committee was the result of a number of experts withdrawing from Friday’s meeting because of conflicts of interest.
“Although this group is small, it contains the appropriate expertise needed to have a robust discussion on the topic at hand today,” Buraccio said.
Leqembi is the second Alzheimer’s treatment from Eisai and Biogen to come under FDA review, following the controversial approval of the drug Aduhelm in the summer of 2021.
The drug regulator granted accelerated approval to Aduhelm, developed by the two companies, despite 10 of 11 advisory committee members concluding that the treatment did not demonstrate clinical benefit. A congressional investigation subsequently found that Aduhelm’s approval was “riddled with irregularities.”
Sen. Bernie Sanders, chairman of the Senate Health Committee, told the Department of Health and Human Services in a letter Wednesday that “FDA has a special responsibility to restore public trust after the inappropriate relationship with Biogen during the agency’s review of a previous illness of Alzheimer’s drug, Aduhelm.”
FDA sees clinical benefit
Eisai’s study of Leqembi found that the drug slowed cognitive decline in early Alzheimer’s patients by 27%. The antibody is administered twice a month by intravenous infusion. It targets a protein called amyloid, often called plaque, that builds up in the brain and is associated with the disease.
Buracchio told the group that the agency views these results as clinically relevant to patients. Several families whose loved ones have been diagnosed with Alzheimer’s disease told the panel during the public comment section that Leqembi has given them hope.
Joan Bridges told the panel that Lekemby had helped her husband Jerome continue his daily activities, which had improved their lives: “Going from hopelessness to hope for our future was made possible by Lekemby – a new life,” Bridges told the panel
“Alzheimer’s disease is a terrible, crippling disease for patients and their caregivers,” Bridges said. “The fact that Leqembi can slow the process is a huge step in fighting the disease and making life more rewarding for those diagnosed with Alzheimer’s.”
But Leqembi also carries serious risks of brain swelling and bleeding. During the study, 13% of patients receiving Leqembi experienced swelling and 14% experienced bleeding.
Swelling and bleeding are usually mild with no obvious symptoms, but these episodes can be life-threatening, according to the FDA.
There were three deaths in the study that were possibly related to Leqembi, although the FDA was unable to draw definitive conclusions in its review.
Two patients who died had cerebral hemorrhages after the infusion. They were given blood thinners. A third patient who died had an underlying condition called cerebral amyloid angiopathy, in which the blood vessels in the brain are weak, which can lead to bleeding.
Dr. Deniz Erten-Lyons, an FDA official, told the group that taking blood thinners during treatment with Leqembi may increase the risk of brain bleeds.
Several groups voiced strong opposition to the FDA’s approval of Leqembi during the public comment section of Friday’s meeting.
Nina Zeldes of Public Citizen’s Health Research Group said the FDA has not clearly presented convincing evidence that Leqembi has clinical benefit. Zeldes said the serious safety concerns associated with the treatment outweigh the benefit based on the current data.
Dr. Donna Kim Murphy, a neuroscientist with Doctors for America, said the Eisai study was flawed because black Americans, who are at higher risk for Alzheimer’s disease, were severely underrepresented in the trial. Black Americans accounted for 2.3% of participants who received Leqembi during the trial.
“With the racial incidence of Alzheimer’s and cerebral hemorrhage in black patients and their significant underrepresentation in this study, I as a neurologist cannot advise this group with data on lecanemab,” Murphy said.
Small panel due to conflict of interest
Buraccio said the panel was smaller than usual due to the withdrawal of experts due to conflicts of interest.
The FDA’s decision on who to include in Friday’s meeting was influenced by a letter from the Alzheimer’s Association, which advocated for full approval of Leqembi, Burrachio said. At least one FDA advisory committee member, Dr. David Weissman, signed this letter.
Weisman was initially granted permission to participate in Friday’s meeting despite serving as principal investigator for Biogen and Eisai clinical trials of Leqembi and Aduhelm at Abington Neurological Associates.
Weissman subsequently withdrew from the meeting and did not participate.
Incumbent Dr. Robert Alexander was cleared to chair the panel on Friday, despite owning up to $150,000 worth of stock in companies that compete with Eisai and Biogen. The FDA disclosure did not name the companies.
Alexander is the Chief Scientific Officer of the Alzheimer’s Prevention Initiative at the Banner Alzheimer’s Institute. Banner is conducting an Alzheimer’s clinical trial for a competing firm, and Alexander receives a $50,000 to $100,000 salary a year from funding supporting the trial.
Brian Marshall, who heads the office that manages the FDA’s advisory committees, asked the agency to grant Alexander a waiver because he has unique experience that is “invaluable” to Friday’s meeting.
Medicare coverage, pricing controversy
Leqembi is technically already on the US market after receiving fast-track approval in January, but very few seniors have access to the expensive treatment because Medicare limits coverage to people who participate in clinical trials. No clinical trials are conducted.
As a result, most older people only have access to Leqembi if they can afford to pay for the drug out of pocket. Leqembi has a list price of $26,500 per year.
Medicare promised to broadly cover Leqembi the same day the FDA fully approved the drug. The Veterans Health Administration already covers treatment for veterans.
Sen. Sanders said Leqembi’s price was “reckless” and urged HHS Secretary Xavier Becerra to take action to lower the price in a letter ahead of this week’s meeting.
Sanders said seniors would face significant out-of-pocket costs even if Medicare covered Leqembi. The cost of the drug would also put a significant financial burden on the seniors program, raising premiums even for people who don’t use the drug, he said.