Despite winning approvals in a range of countries like the U.S., China, Japan and Israel, Eisai and Biogen’s anti-amyloid Alzheimer’s disease med Leqembi has come up short in the eyes of European regulators.
Friday, drug reviewers at the European Medicines Agency (EMA) recommended against marketing authorization for the partners’ antibody Leqembi, or lecanemab.
Although patients on Leqembi scored better than placebo on the Clinical Dementia Rating Scale Sum of Boxes—an index used to measure dementia severity—the difference between the two groups was “small,” the EMA noted in a fact sheet.
Ultimately, the agency ruled that the positive effects of Leqembi on delaying cognitive decline “do not counterbalance the risk of serious adverse events.”
Unlike its controversial predecessor Aduhelm, Leqembi didn’t stir up much debate around its approvability in the U.S. As Biogen has stopped making Aduhelm, Leqembi has become a key part of the company’s plan for a business turnaround.
However, the EMA has flagged the risk of patients developing the known amyloid antibody side effect, amyloid-related imaging abnormalities, or ARIA.
“Although most cases of ARIA in the main study were not serious and did not involve symptoms, some patients had serious events, including large bleeds in the brain which required hospitalization,” EMA said in its rationale for the rejection.
The regulator also noted that the risk of ARIA is greater in people who have a certain form of the gene for the protein apolipoprotein E (ApoE4). People with two copies of the ApoE4 gene are at the greatest risk of developing the side effect and are also known to be at risk for Alzheimer’s, making them “likely to become eligible for treatment with Leqembi,” EMA said.
Biogen, Eisai and Eisai’s Alzheimer’s development partner BioArctic confirmed the rejection in separate press releases expressing the companies’ disappointment.
“We are extremely disappointed by the CHMP’s negative opinion and understand that this may also be disappointing for the wider Alzheimer’s disease (AD) community,” Lynn Kramer, M.D., chief clinical officer at Eisai, said in a statement.
BioArctic, from which Eisai licensed lecanemab back in 2007, was similarly vexed.
“We are surprised and very disappointed by the CHMP’s opinion posted today,” BioArctic CEO Gunilla Osswald said in an emailed statement. “Foremost, the negative opinion adopted by the CHMP is sad for all patients, caregivers and healthcare professionals in the EU who will now have to wait longer for a treatment which can effectively change the course of this devastating disease.”
Still, Osswald stressed that “[t]his is not the final verdict.”
Eisai, in its own release, noted that it will seek reexamination of the negative opinion and work with regulators to ensure Leqembi is available for Alzheimer’s patients in Europe “as soon as possible.”
Despite the setback, some analysts continue to hold out hope for Leqembi in Europe.
In a Friday note to clients, Mizuho Securities said it figured the news was "more of a delay in the Leqembi European application" rather than an outright rejection. The team noted Leqembi has "some of the best data" it's seen in Alzheimer's development to date and highlighted both the continuing unmet need in the disease, as well as Leqembi's various global approvals.
The rejection comes several months after European regulators delayed their approval decision on Leqembi in late March. The drug has been under review in Europe since January 2023, according to Reuters.
Curiously, the delay was due to an EU court ruling, and not Leqembi itself, which had "implications on EMA's policy on the handling of competing interests of experts,” Eisai said in a statement at the time.
Outside of Europe, Leqembi is approved in the U.S., Japan, China, South Korea and Israel. The antibody is currently marketed in the U.S., Japan and China. Eisai is in charge of development and regulatory approval for the drug, while Biogen is chipping in on commercialization in the U.S., Europe and beyond. BioArctic, for its part, will commercialize Leqembi in the Nordic Region should the companies snare a European approval.
The setback comes shortly after Eli Lilly’s rival Alzheimer’s antibody, donanemab, scored its first approval in the U.S.
The FDA in early July cleared donanemab, branded as Kisunla, to treat adults with early symptomatic Alzheimer’s, including people with mild cognitive impairment and those in the mild dementia stage of the neurodegenerative disease.
Editor's note: This story has been updated with additional context from a Mizuho Securities analyst note.