US FDA adcom supports Leqembi for full approval

Karen Carey, Bio World, June 9, 2023

Eisai Co. Ltd. and Biogen Inc.’s Leqembi (lecanemab) gained the support of the U.S. FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC or adcom) in a 6-0 vote on June 9, as panel members unanimously agreed that the results of the phase III Clarity trial verified the clinical benefit in the treatment of Alzheimer’s disease (AD).

The FDA does not have to follow the adcom’s recommendation, but it often does. The PDUFA date for the supplemental NDA is July 6.

Committee members discussed a change they would like to see made to the Leqembi label, however, one that would require Apolipoprotein E (ApoE) testing. Currently on the label physicians are advised to “consider” testing. Panelists also raised concerns over use of the drug in patients on anticoagulant agents and those with cerebral amyloid angiopathy, although the majority did not want to exclude patients from treatment, and agreed label warnings are sufficient. Even with the warnings, the members insisted more research should be done in those vulnerable to the side effects.

Aside from infusion-related reactions, 75% of which occurred with the first dose, a top adverse event discussed was amyloid-related imaging abnormalities (ARIA), including edema or effusion (ARIA-E) in 0.8% (0% placebo) and microhemorrhages and superficial siderosis (ARIA-H) in 0.6% (0.1%) of drug-treated patients. The effects were higher in those who were carriers vs. non-carriers of ApoE: 15.8% vs. 5.4% for ARIA-E and 17.3% vs. 9% for ARIA-H.


The trial included 1,795 patients, including 897 receiving placebo and 898 receiving lecanemab.

Out of those on lecanemab, three experienced severe symptomatic cases of ARIA-E involving a seizure or aphasia and requiring hospitalization. Irizarry said the company intends to monitor ARIA through MRIs prior to the fifth, seventh and 14th infusions and by educating patients to identify and report any symptoms.

During the open hearing section of the adcom, numerous patients and their caregivers spoke, all in support of Leqembi’s full approval. Joanne Bridges retired to Florida in 2013 but her husband, Jerome, was diagnosed with early Alzheimer’s in October of 2019 before participating in a Leqembi clinical trial.


“By receiving Leqembi he became more talkative, smiled, started reading again … and listened to his favorite jazz music,” Joanne said. “My day to day became less stressful. We take short walks. We go to the beach … We dine out with friends and enjoy life.”

Those opposing the approval included representatives of the Public Citizen’s Health Research Group, the National Center for Health Research (NCHR) and Pharmed Out. They pointed to a small difference between treatment and placebo through one measure. Diana Zuckerman, president of NCHR, noted that “up to 50% of people with mild cognitive impairment revert to non-impairment status on their own” without drug intervention. “Alzheimer’s is not inevitable for this population,” she said, stressing the drug’s risks.


The members favored the benefit/risk profile for ApoE ε4 but thought physicians should be required to test patients prior to starting Leqembi treatment. They were split on the use of anticoagulants, with a few members saying there was too much uncertainty. There was also concern among members who said they were “nervous” about prescribing Leqembi for patients with CAA. Two deaths were reported when Eisai and Biogen presented their Clarity data last November.

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