• The FDA's independent advisors unanimously said the Alzheimer's drug Leqembi demonstrated a clinical benefit to patients.
• The vote in favor of Leqembi could pave the way for full FDA approval on July 6.
• Medicare has promised to broadly cover Leqembi, which costs $26,500 per year, if the FDA grants full approval of the treatment.
• The FDA advisory panel was unusually small, just six members, due to at least one member recusing himself due to a conflict of interest.

A panel of independent advisors to the Food and Drug Administration on Friday unanimously endorsed the Alzheimer's drug Leqembi made by Eisai and Biogen, paving the way for full approval of the treatment this summer. 

The advisors voted 6-0 that Eisai's data demonstrated a clinical benefit to patients. The FDA is not required to follow the advisors' 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 program for seniors is severely restricting coverage of Leqembi right now because it was previously approved through an expedited process.

Eisai has set the annual list price of Leqembi at $26,500 per year.

The advisory committee for Leqembi was unusually small, with just six voting members.

Dr. Teresa Buracchio, acting head of the FDA's neuroscience office, said the smaller-than-usual committee resulted from a number of experts recusing themselves from Friday's meeting due to conflicts of interest.

"While this group is small, it contains the appropriate expertise necessary to have a robust discussion on the topic at issue today," Buracchio said.

Leqembi is the second Alzheimer's treatment from Eisai and Biogen to come under FDA review, after the controversial approval of the drug Aduhelm in the summer of 2021.

The drug regulator granted expedited approval to Aduhelm, developed by the two companies, despite 10 out of 11 advisory committee members concluding that the treatment did not demonstrate a clinical benefit. A congressional investigation subsequently found that the approval of Aduhelm was "rife with irregularities."

Sen. Bernie Sanders, chair of the Senate Health Committee, told the Health and Human Services Department in a letter Wednesday that the "FDA has a special responsibility to restore the public trust after its inappropriate relationship with Biogen during the agency's review of a prior Alzheimer's drug, Aduhelm."

FDA sees clinical benefit, but there are risks

Eisai's study of Leqembi found the drug slowed cognitive decline in early Alzheimer's patients by 27%. The antibody is administered twice monthly through intravenous infusion. It targets a protein called amyloid, often referred to as plaque, that builds up in the brain and is associated with the disease.

Buracchio told the panel that the agency views these results as clinically meaningful for patients.

But Leqembi also carries serious risks of brain swelling and bleeding. During the study, 13% of patients who received Leqembi had swelling and 14% had bleeding.

The swelling and bleeding are normally mild without obvious symptoms, but these episodes can be life-threatening, according to the FDA.

There were three deaths in the study that are possibly related to Leqembi, though the FDA was unable to draw definitive conclusions in its review.

Two patients who died suffered cerebral hemorrhages after receiving the infusions. They had been administered blood thinner medications. 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 panel that taking blood thinners during treatment with Leqembi might increase the risk of cerebral hemorrhages.

Several groups expressed strong opposition to FDA approval of Leqembi during the meeting's public comment section Wednesday. 

Nina Zeldes with the Public Citizen's Health Research Group said the FDA has not been presented with clearly compelling evidence that Leqembi has a clinical benefit. Zeldes said serious safety concerns associated with the treatment outweigh the benefit based on the current data. 

Dr. Dona Kim Murphey, a neurologist with Doctors for America, said Eisai's study was flawed because Black Americans, who are at higher risk of Alzheimer's disease, were severely underrepresented in the trial. Black Americans represented 2.3% of participants who received Leqembi during the trial.

"With racialized instance of Alzheimer's and brain bleeding in Black patients and with their significant underrepresentation in this trial, I cannot as a neurologist advise this group with lecanemab data," Murphey said.

Small panel due to conflicts of interest

Buracchio said panel was smaller than usual due to experts recusing themselves due to conflicts of interest.

The FDA's decision on whom to include in Friday's meeting was impacted by a letter from the Alzheimer's Association that advocated for Leqembi's full approval, Burrachio said. At least one member of the FDA advisory committee, Dr. David Weisman, signed that letter.

Weisman was originally granted a waiver to participate in Friday's meeting despite serving as the principal investigator for Biogen and Eisai clinical trials on Leqembi and Aduhelm at Abington Neurological Associates.

Weisman subsequently recused himself from the meeting and did not participate.

Acting Chair Dr. Robert Alexander was granted a waiver to lead the panel Friday despite holding stocks valued up to $150,000 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 $50,000 to $100,000 in salary per year from funding supporting the trial.

Bryan Marshall, who heads the office that manages the FDA's advisory committees, asked the agency to grant Alexander a waiver because he has unique expertise that is "invaluable" to Friday's meeting.

Medicare coverage, price controversy

Leqembi is technically already available on the U.S. market after receiving fast-track approval in January, but very few seniors can access the expensive treatment because Medicare is restricting coverage to only people who are participating in clinical trials. There are no clinical trials underway.

As consequence, most seniors can only access Leqembi if they can afford to pay for the drug out of pocket. Leqembi has a list price of $26,500 per year.

Medicare has promised to broadly cover Leqembi on the same day the FDA fully approves the drug. The Veterans Health Administration is already covering the treatment for veterans.

Sen. Sanders said the price of Leqembi is "unconscionable" and called on HHS Secretary Xavier Becerra to take action to slash the price in a letter ahead of the meeting this week.

Sanders said seniors would face substantial out-of-pocket costs even if Medicare covers Leqembi. The price of the drug would also put a substantial financial burden on the program for seniors, raising premiums even for people who are not using the medication, he said.