The FDA will allow a new dosing schedule for Eli Lilly’s Alzheimer’s drug Kisunla that could lessen a known side effect of the monoclonal antibody drug class that has led to several deaths.
Eli Lilly’s Alzheimer’s drug Kisunla is receiving a label update that the company hopes will give it an edge over Biogen and Eisai’s rival medicine Leqembi. The new dosing schedule, approved by the FDA on Wednesday, reduces the burden of severe side effects of the anti-amyloid antibodies that have led to death in several cases and have challenged the uptake of the first disease-modifying treatment options for the devastating neurodegenerative condition.
Kisunla can now be administered more gradually in the first few months of treatment as patients get up to the recommended monthly dose. The drug was approved in July 2024 for early symptomatic Alzheimer’s disease with a titration schedule of 700-mg intravenous infusion for the first three monthly doses, followed by 1,400-mg doses on a continued monthly schedule until plaques in the brain clear.
This new label update is intended to mitigate safety concerns that have dogged the drug class since rival Eisai and Biogen received approval for Leqembi in January 2023. It was the first drug approved for Alzheimer’s in decades and the first that proclaimed to alter the underlying disease.
Lilly followed Leqembi to the market with Kisunla, but the FDA at time of approval raised concerns about an imbalance of deaths in patients who took Kisunla compared with placebo. The adverse event of concern is known as amyloid-related imaging abnormalities (ARIA) and can show up on brain scans as swelling (ARIA-E) or bleeding in the brain (ARIA-H). It’s typically asymptomatic but can be fatal. Kisunla and Leqembi currently carry a boxed warning for ARIA-E.
In order to mitigate the safety concerns, Lilly continued testing new dosing strategies after approval. The TRAILBLAZER-ALZ 6 study read out in October 2024 showing that lower doses of 350 mg for initial treatment, 700 mg for the second, then 1,050 mg for the third decreased the incidence of ARIA-E by 41% at week 24. At 52 weeks, the risk was reduced by 35%.
Efficacy, meanwhile, was the same as expected from previous studies of Kisunla, which showed that the drug removed amyloid plaques to minimal levels. The removal of plaques has been associated with a slowing of cognitive decline.
Lilly hopes the label update will “aid healthcare professionals in evaluating appropriate treatment options for their patients,” Brandy Matthews, vice president of Global & US Medical Affairs for Alzheimer’s disease at the company, said in a prepared statement.
The safety issues have not been the only hurdle Lilly and Biogen/Eisai have faced as they try to market these new Alzheimer’s drugs. Despite being heralded as a breakthrough for a universally fatal disease that has long lacked treatment options, monoclonal antibodies have not seen significant uptake. Leqembi reportedly had sales of $22.8 million in May while Kisunla brought in $11 million for the same month, according to Jefferies.
Both companies have said that healthcare providers lack access to the testing infrastructure needed to ensure the disease can be diagnosed effectively to get patients on the drugs.
Meanwhile, the approval of these drugs has boosted investment in the Alzheimer’s space. Global Data recently found that deal value for Alzheimer’s-focused companies jumped 780% from just $2 billion in 2022 to $18 billion in 2024.
