FDA Approves Label Change for Alzheimer’s Amyloid Drug

The FDA approved a label update with a new titration schedule for donanemab (Kisunla), an anti-amyloid drug approved to treat early symptomatic Alzheimer’s disease, drugmaker Eli Lilly said.

The move was designed to reduce the risk of a potentially serious or fatal adverse event — known as amyloid-related imaging abnormalities with edema and effusion (ARIA-E) — while maintaining sufficient amyloid reduction.

Donanemab is administered as a monthly intravenous infusion. The original dosing plan called for 700 mg (two 350 mg vials) every 4 weeks for three doses, followed by 1,400 mg every 4 weeks after that. The new dosing regimen shifts one 350 mg vial of donanemab from the first dose to the third dose, delivering the same amount of drug by week 24.

In the TRAILBLAZER-ALZ 6 study, the modified titration schedule significantly lowered the incidence of ARIA-E versus the original dosing schedule while still achieving similar levels of amyloid plaque removal.

Findings from TRAILBLAZER-ALZ 6, which were presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) meeting, showed that the frequency of ARIA-E was 13.7% in the modified titration arm compared with 23.7% in the standard arm, at week 24.

“We were able to demonstrate that one of the dosing paradigms — the modified titration arm — did achieve success in lowering ARIA-E rates,” Eli Lilly’s John Sims, MD, said at the CTAD meeting. “That was accompanied by lower symptomatic frequencies, lower radiographic severities, and a fairly dramatic impact on the [APOE4] homozygous population.”

Donanemab was approved by the FDA in July 2024 to treat adults with early symptomatic Alzheimer’s disease with confirmed amyloid pathology. The agency’s decision was based on results of the phase III TRAILBLAZER-ALZ 2 trial, in which donanemab slowed clinical progression relative to placebo (P<0.001).

In the pivotal trial, 24% of donanemab-treated participants had ARIA-E and 31.4% had ARIA with cerebral microhemorrhages and hemosiderin deposits (ARIA-H). Two ARIA-related deaths were attributed to donanemab in that study. ARIA occurred more frequently in APOE4 homozygotes than in heterozygotes or noncarriers.

The prescribing information for donanemab includes a boxed warning for ARIA and says APOE4 testing should be performed before starting treatment. ARIA-E is usually asymptomatic, although serious and fatal events can occur.

The warning also cautions that serious intracerebral hemorrhages, including fatal hemorrhages, have been seen with this class of medications.

Donanemab currently is being studied in several clinical trials, including TRAILBLAZER-ALZ 3, which is evaluating the drug’s potential to reduce the risk of disease progression in people with asymptomatic Alzheimer’s.

MedPage Today. She writes about brain aging, Alzheimeru2019s disease, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinsonu2019s disease, ALS, concussion, CTE, sleep, pain, and more. Judy started her career with the Congressional watchdog agency GAO and has been a magazine reporter, academic text editor, and radio producer. She holds a BA in English from University of Detroit, MBA from Xavier University, and attended Columbia Radcliffe Publishing Course. Besides writing about neurology, sheu2019s reported on topics ranging from mental health to environmental contamination. Her work has been published in outlets as diverse as Business Week, Conde Nast’s Self, and AlterNet.”,”affiliation”:””,”credential”:””,”url_identifier”:”jg8109″,”avatar_url”:””,”avatar_alt_text”:”Judy George”,”twitter”:”https://twitter.com/MedPageNeuro”,”byline”:”Deputy Managing Editor, MedPage Today”,”full_name”:”Judy George”,”title”:”Deputy Managing Editor, MedPage Today, “,”url”:”https://www.medpagetoday.com/people/jg8109/judy-george”}]”>