Ryan Cross
Senior Science Correspondent
Eli Lilly’s new Alzheimer’s drug is off to a slow start, but the Indianapolis drugmaker hopes that an update to the treatment’s prescription label may help build confidence among doctors and patients who have been hesitant to try it.The FDA has approved a new dosing regimen for Kisunla, which significantly lowers the risk of brain swelling, one of the potential side effects associated with antibody therapies that remove amyloid from the brain.
The Kisunla update could help level the playing field with a competing drug sold by Eisai and Biogen. It may also play an important role in an ongoing reassessment in Europe, after drug evaluators recently recommended against Lilly’s drug.
Brandy Matthews
Brandy Matthews, Lilly’s VP of global & US medical affairs for Alzheimer’s, told Endpoints News that the update “should have a positive impact for patients and likely grow confidence across clinicians in their use in the US.”
The dosing change is based on data from a new Phase 3 study of more than 800 patients in the early stages of Alzheimer’s.
After 24 weeks of treatment, a slightly slower ramp-up of the drug’s dose reduced the relative risk of brain swelling by 41% compared to the older dosing schedule. The relative risk was reduced by 35% after one year of treatment.
Matthews said the new dosing provides the same reduction in amyloid and the same lowering of blood biomarkers associated with the disease as the old dosing.
Lilly reported $21 million in sales of Kisunla in the first quarter of 2025, a far cry from the billions of dollars that experts once imagined a long-sought Alzheimer’s drug would reap. Concerns about brain bleeding and swelling, measured as amyloid-related imaging abnormalities (ARIA) — which have been fatal for some patients — have likely stymied uptake.
The committee responsible for evaluating new drugs in Europe recommended in March that regulators reject Kisunla due to high rates of ARIA and three patient deaths from the drug. The committee also rejected Biogen and Eisai’s Leqembi before reversing course. It recently said that it would reexamine Kisunla.
Matthews said the reexamination was “ongoing” and noted that the data supporting the new and safer dosing strategy were published in April.
Searching for a safer dose
According to ClinicalTrials.gov, Lilly began its study searching for a safer dosing strategy at the end of February 2023, just a couple of months before announcing the results of the larger 1,700-person trial of the drug, which was used as the basis for FDA approval last summer.
The new study compared the standard dosing of Kisunla to three new dosing regimens, with about 200 people in each group.
The method that worked best, and the one that the FDA just approved, is simple. Rather than infusing two 350 mg vials of the drug during each of the first three sessions, patients get one vial during the first session, two vials in the second session and three vials in the third session. The full dose of four vials each month for the fourth session onward is unchanged.
In Lilly’s original study, 24% of treated patients had brain swelling, known as ARIA-E. In Eisai’s study, the side effect was only detected in 13% of patients. In Lilly’s new study, 14% of patients with modified dosing developed ARIA-E compared to 24% of patients who got the original dosing.
The results for brain bleeding, known as ARIA-H, were not as clear-cut.
In Lilly’s prior study, 31% of patients had ARIA-H compared to 17% of patients in Eisai’s study. In Lilly’s new study, about 25% of patients who got the original dosing developed ARIA-H, compared to 20% who got the modified titration. The difference was not statistically significant.
