EU CHMP Rejects Biogen and Eisai's Alzheimer’s Drug Leqembi

Eisai and Biogen’s Alzheimer’s disease therapy, Leqembi (lecanemab), has faced a setback in its expansion into the European market. The European Medicines Agency (EMA) has paused the approval process following a recommendation from its drug review committee against the therapy’s approval.

The Committee for Medicinal Products for Human Use (CHMP) expressed concerns over the balance between the drug's benefits and its potential risks. They stated that the positive effects on slowing cognitive decline were “not large enough” to outweigh the risk of serious side effects. Eisai responded swiftly, indicating their intention to re-assess the CHMP's opinion.

A significant concern for the committee was the risk of amyloid-related imaging abnormalities (ARIA), which can be identified exclusively through MRI scans. ARIA can manifest as oedema, effusion, or hemorrhage. Most ARIA cases identified in the primary study were not severe and did not exhibit symptoms. However, some instances led to serious outcomes, including significant brain bleeds that necessitated hospitalization. The risk of developing ARIA was higher in patients with the ApoE4 gene, a genetic variant that predisposes individuals to Alzheimer’s disease.

Additionally, the CHMP highlighted the minimal difference in the improvement of cognitive decline between patients treated with Leqembi and those given a placebo. This was measured using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. The committee emphasized that the seriousness of the side effects needs to be weighed against the modest benefits observed.

Leqembi operates by targeting the amyloid plaques that accumulate in the brain, a characteristic feature of Alzheimer’s disease and a presumed cause of memory and cognitive impairment. The drug had initially received accelerated approval from the US Food and Drug Administration (FDA) in January, which was recently upgraded to full approval.

For Biogen, Leqembi is a crucial drug, developed in collaboration with Eisai, particularly after Biogen ceased the development of its other Alzheimer's treatment, Aduhelm (aducanumab-avwa), in January. Projections by GlobalData suggest that Leqembi could generate over $6.1 billion in sales by 2030.

Eisai and Biogen have also submitted a supplemental biologics application (sBLA) to the US FDA for monthly Leqembi intravenous (IV) maintenance dosing for Alzheimer’s patients. The Prescription Drug User Fee Act (PDUFA) action date for this application is set for January 25, 2025.