The Alzheimer’s drug Leqembi is seen on this undated news image obtained by Reuters on January 20, 2023.
Hey | via Reuters
A panel of independent advisers from the Food and Drug Administration unanimously endorsed Leqembi, an Alzheimer’s drug produced by Hey AND Biogenpaving the way for full treatment approval this summer.
Advisors voted 6-0 that Eisai’s data showed clinical profit to patients. The FDA will not be obligated to follow the advisers’ recommendations, but the panel’s vote on Leqembi will make a giant difference in favor of full approval.
The FDA is predicted to make a final decision on Leqembi on July 6. The agency’s decision will determine whether Medicare covers treatment broadly. The senior program is currently severely limiting Leqembi’s reach because it was previously approved through an accelerated process.
Eisai has set Leqembi’s annual list price at $26,500 a 12 months, meaning most patients cannot afford treatment without Medicare coverage.
Leqembi’s advisory committee on Friday was extremely small, with just six voting members.
Dr. Teresa Buracchio, acting head of the FDA’s neuroscience office, said the smaller-than-usual committee was attributable to many experts withdrawing from Friday’s meeting attributable to conflicts of interest.
“While this group is small, it comprises the relevant expertise obligatory to have a solid discussion on the topic today,” Buracchio said.
Leqembi is the second Alzheimer’s drug from Eisai and Biogen to be reviewed by the FDA, following the controversial approval of Aduhelm in the summer of 2021.
The medicines regulatory body has expedited approval for Aduhelm, developed by the two corporations, though 10 of the 11 members of the advisory committee said the treatment showed no clinical profit. A Congressional investigation subsequently found that Aduhelm’s approval was “riddled with irregularities.”
Senator Bernie Sanders, chairman of the Senate Health Committee, said in a letter to the Department of Health and Human Services on Wednesday that “the FDA has a special responsibility to revive public trust after an inappropriate relationship with Biogen during the agency’s review of an earlier Alzheimer’s study.” drug, Adhelm.
The FDA recognizes the clinical advantages
A study by Eisai on Leqembi found that the drug slowed cognitive decline in patients with early-onset Alzheimer’s disease by 27%. The antibody is given twice a month as an intravenous infusion. It targets a protein called amyloid, sometimes called plaque, which builds up in the brain and is related to disease.
Buracchio told the panel that the agency considers these results to be clinically significant for patients. Several families whose family members were diagnosed with Alzheimer’s disease told the panel during the public comment section that Leqembi had given them hope.
Joanne Bridges told the panel that Leqembi helped her husband Jerome proceed his day by day activities, which improved their lives: “The transition from hopelessness to hope for our future was made possible by Leqembi – a recent life,” Bridges told the panel
“Alzheimer’s is a terrible, devastating disease for patients and their caregivers,” said Bridges. “The indisputable fact that Leqembi can slow this process is a large step in fighting the disease and making life more beneficial for people diagnosed with Alzheimer’s.”
Serious risk
But Leqembi also carries a serious risk of brain swelling and bleeding. During the study, 13% of the patients receiving Leqembi developed swelling and 14% had bleeding.
Swelling and bleeding are often mild with no obvious symptoms, but these episodes will be life-threatening, based on the FDA.
The study reported three deaths believed to be related to Leqembi, although the FDA was unable to attract definitive conclusions in its review.
Two of the deceased patients suffered a cerebral hemorrhage after receiving an infusion. They got blood thinners. The third patient who died had an underlying condition called cerebral amyloid angiopathy, wherein the blood vessels in the brain are weak, which might result in bleeding.
Deniz Erten-Lyons, an FDA official, told the panel that taking blood thinners during treatment with Leqembi could increase the risk of cerebral hemorrhage.
Several groups expressed strong opposition to the FDA’s approval of Leqembi during Friday’s comment section at the meeting.
Nina Zeldes z Public citizenThe Health Research Group said the FDA had not received clear convincing evidence that Leqembi had clinical advantages. Zeldes said the serious safety concerns with the treatment outweigh the advantages based on current data.
Dr. Dona Kim Murphey, neurologist with Doctors for America, said the Eisai study was flawed because black Americans, who’re at higher risk for Alzheimer’s disease, were significantly underrepresented in the study. Black Americans accounted for 2.3% of the participants who received Leqembi during the trial.
“With the racist cases of Alzheimer’s disease and cerebral bleeds in black patients, and their significant underrepresentation on this study, as a neurologist, I cannot advise this group with the drug drug data,” Murphey said.
Small panel attributable to conflicts of interest
Buracchio said the panel was smaller than usual because experts withdrew attributable to conflicts of interest.
The FDA’s decision on whom to incorporate in Friday’s meeting was influenced by a letter from Alzheimer’s Association who advocated Leqembi’s full approval, Burrachio said. No less than one FDA advisory committee member, Dr. David Weisman, signed the letter.
Weisman was initially excused from attending Friday’s meeting despite being the principal investigator for Biogen and Eisai’s Leqembi and Aduhelm clinical trials at Abington Neurological Associates.
Weisman later reused alone from the meeting and didn’t take part in it.
The acting chairman was Dr. Robert Alexander granted exemption to steer the panel on Friday, despite owning as much as $150,000 value of stock in corporations competing with Eisai and Biogen. The FDA disclosure didn’t name the corporations.
Alexander is the scientific director of the Alzheimer’s Prevention Initiative at the Banner Alzheimer’s Institute. Banner is conducting an Alzheimer’s disease clinical trial for a competitor, and Alexander is paid between $50,000 and $100,000 a 12 months in research funding.
Bryan Marshall, who heads the office that manages the FDA’s advisory committees, asked the agency to fireplace Alexander because he has unique knowledge that’s “invaluable” at Friday’s meeting.
Medicare coverage, pricing controversy
Leqembi is now technically available in the U.S. market after getting rapid approval in January, but only a few seniors have access to the expensive treatment because Medicare restricts coverage to only people participating in clinical trials. No clinical trials are conducted.
In consequence, most seniors can only access Leqembi in the event that they can afford to pay for the drug out of pocket. Leqembi has an inventory price of $26,500 per 12 months.
Medicare has promised to broadly cover Leqembi on the same day the FDA fully approves the drug. The Veterans Health Administration already covers veterans’ medical expenses.
Senator Sanders said Leqembi’s price was “unscrupulous” and urged HHS secretary Xavier Becerra to take motion to lower the price in a letter ahead of this week’s meeting.
Sanders said seniors can have to pay significant out-of-pocket costs even when Medicare covers Leqembi. He said the price of the drug would also put a major financial strain on the seniors program, raising premiums even for individuals who don’t use the drug.