Eisai and Biogen have announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMA has adopted a negative opinion on granting marketing authorization approval (MAA) for the Alzheimer’s drug Leqembi.
The CHMP cited concerns involving the frequent occurrence of swelling and potential bleedings in the brain of patients who received the treatment, concluding that “the observed effect of Leqembi on delaying cognitive decline does not counterbalance the risk of serious side events associated with the medicine.”
Eisai has responded to the decision by stating its plans to request a re-examination of the CHMP opinion.
“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. AD is an irreversible, neurodegenerative disease that poses significant challenges to those living with AD, their care partners and society,” said Lynn Kramer, Chief Clinical Officer at Eisai. “There is a significant unmet need for new innovative treatment options that target an underlying cause of disease progression. We remain focused on making a meaningful difference to those living with early AD and those closest to them.”
Leqembi is a monoclonal antibody designed to target amyloid-beta proteins, clearing the accumulation of amyloid-beta plaques in the brain of patients with Alzheimer’s disease. Other biologics with a similar mechanism of action include Eli Lilly’s Kinsula (donanemab).
FDA approval
The FDA granted approval to Leqembi in January 2023 as a treatment for early Alzheimer’s disease (AD), including mild cognitive impairment due to AD and mild AD. The biologic drug has also been approved in several other regions including Japan and China.
Eisai and Biogen’s application to the EMA included data from a phase 3 clinical trial named Clarity AD, which recruited over 1,700 patients with Alzheimer’s disease. Those who were treated with Leqembi saw a reduction in the severity of their symptoms of 27% after 18 months compared to those who received a placebo.
While the EMA recognized the drug’s therapeutic benefits, the committee’s main concerns focused on the frequent occurrence of amyloid-related imaging abnormalities (ARIA), a type of side effect involving brain swelling and bleeding. The risk was higher in patients that carry two copies of the ApoE4 gene, who are known to be more likely to develop Alzheimer’s disease and therefore are also more likely to be prescribed a treatment such as Leqembi.
“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 hospitalisation. The seriousness of this side effect should be considered in the context of the small effect seen with the medicine,” stated the EMA.
