The European Medicines Agency’s Committee for Medicinal Products for Human Use found that Leqembi’s benefits do not outweigh the risks of severe side effects associated with the treatment.
The European Medicines Agency’s Committee for Medicinal Products for Human Use announced Friday that it has adopted a negative opinion on Biogen and Eisai’s Alzheimer’s disease treatment Leqembi, citing the risk of side effects associated with the treatment.
The Committee for Medicinal Products for Human Use (CHMP) recommended not granting a marketing authorization for Leqembi. The committee contends that the effect of the delay of cognitive decline from the drug does not “counterbalance the risk of serious side events.” This is due to the “frequent occurrence” of amyloid-related imaging abnormalities (ARIA), which involves swelling and potential bleeding in the brain.
The CHMP also noted its concerns that the risk of ARIA is more pronounced in people who have a particular form of the gene for the protein apolipoprotein E, also called ApoE4. The risk for these patients is highest in people with two copies of the ApoE4 gene, who are at risk of developing Alzheimer’s and who would seek Leqembi as a potential treatment.
Ultimately, the CHMP said Leqembi’s benefits were “not large enough” to outweigh the risks. During Leqembi’s approval process in the U.S., issues over ARIA were brought up in FDA briefing documents, but a panel of external advisors found the risk-benefit profile acceptable.
“We are extremely disappointed by the CHMP’s negative opinion and understand that this may also be disappointing for the wider Alzheimer’s disease community. [Alzheimer’s disease] is an irreversible, neurodegenerative disease that poses significant challenges to those living with [Alzheimer’s], their care partners and society,” Lynn Kramer, chief clinical officer at Eisai, said in a statement.
Eisai will seek a reexamination and plans to work with the “relevant authorities” to get approval into the European Union. Jefferies analysts in a note to investors said that such a process could take around 60 days of active review and that around 39% of EU reexaminations become positive. However, analysts opined that expectations at this point “would be very low” and that a narrow label could result.
“While this is another setback for [Biogen], we are reminded that at least 2/3 of Leqembi sales estimates are forecast from the U.S., where it continues to grow steadily,” Jefferies analysts wrote.
Jefferies analysts are focused on the subcutaneous submission and approval that should come next year, which is expected to drive sales up further. They predict Leqembi’s sales for the second quarter of 2024 to be around $30 million.
Bank of Montreal Capital Markets analysts noted that Europe is not the largest market for the drug. However, it does characterize a “significant revenue opportunity” that can help speed up a “slow-building launch.” The analysts estimate peak Leqembi revenues in the EU to be $1.6 billion.
In the first quarter of 2024, the drug pulled in around $19 million in sales. The monoclonal antibody is already approved in the U.S., Japan, China, South Korea, Hong Kong and Israel.
