FDA Approves Lilly's Kisunla Dosing Adjustment to Reduce Brain Swelling Risk

In a significant development in the field of Alzheimer's treatment, Eli Lilly has achieved a notable success with its medication Kisunla (donanemab-azbt). The U.S. Food and Drug Administration (FDA) has approved a revised dosing schedule for Kisunla that considerably lowers the risk of brain swelling, while maintaining its effectiveness in eliminating harmful amyloid plaques. This modification is based on findings from the Phase IIIb TRAILBLAZER-ALZ 6 study, which demonstrated that a gradual increase in dosage reduced the occurrence of amyloid-related imaging abnormalities with oedema (ARIA-E) by 41% at 24 weeks, and by 35% at one year when compared to the previous dosing plan.

Instead of changing the total drug quantity administered, Lilly adjusted the distribution of doses over the first three infusions. Initially, patients received two 350-mg vials for each of the first three monthly doses, which then increased to four vials starting from the fourth infusion. The newly approved dosing strategy introduces a more gradual ramp-up: one vial at the first infusion, two vials at the second, three at the third, followed by the full four-vial dose beginning in the fourth month. This modified titration approach reduced ARIA-E incidence to 14% at 24 weeks, down from 24% with the standard dosing. At 52 weeks, the reduced risk persisted, with 16% experiencing ARIA-E under the new schedule compared to 25% with the original approach. Importantly, the reduction of amyloid plaques and P-tau217 remained effectively unchanged between the two regimens.

Brandy Matthews, the Vice President of Global and US Medical Affairs for Alzheimer's Disease at Lilly, expressed confidence in the updated label for Kisunla, emphasizing its potential to assist healthcare professionals in making informed treatment choices for their patients. This update addresses a critical competitive issue for Kisunla, which had previously shown higher rates of ARIA-E and brain microbleeds relative to Eisai and Biogen's Leqembi (lecanemab) during clinical trials.

Despite being launched 18 months after Leqembi received its initial approval, Kisunla has rapidly gained market traction, with its US sales rising by 46% in March, compared to a 17% increase for Leqembi in the same timeframe. A part of Kisunla’s appeal lies in the possibility of discontinuing treatment once amyloid plaques are cleared, potentially within six months, and its regimen of once-monthly administration from the beginning. In contrast, Leqembi requires an 18-month biweekly regimen before transitioning to a monthly schedule.

The competitive environment in Alzheimer's treatments may undergo further changes, as the FDA is expected to announce a decision by August 31 regarding a weekly maintenance dose of subcutaneous Leqembi, which could potentially enhance sales for Eisai and Biogen's therapy. However, recent surveys indicate that systemic challenges continue to hinder the wider adoption of both therapies. Neurologists report an average delay of seven weeks from the initial treatment discussion to drug administration, with 90% of them finding the process of determining patient eligibility at least somewhat challenging.