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Eli Lilly’s new Alzheimer’s drug, donanemab, significantly slows cognitive and functional decline in people with early symptomatic Alzheimer’s disease (AD), according to full results from the Phase III TRAILBLAZER-ALZ 2 study. The results support Lilly’s application for regulatory approval to treat people with amyloid-positive early symptomatic Alzheimer’s disease (either mild cognitive impairment or mild dementia), regardless of their baseline level of tau.

“The results of this study reinforce the importance of diagnosing and treating disease sooner than we do today,” said Mark Mintun, MD, group vice president Neuroscience Research & Development at Lilly, and president of Avid Radiopharmaceuticals.

The data were shared at the 2023 Alzheimer’s Association International Conference (AAIC) and simultaneously published in the Journal of the American Medical Association (JAMA).

Earlier this month, the FDA granted full approval to Eisai and Biogen’s Leqembi (leconemab), which was heralded as the first drug for this disease that slows progression.

“If approved, we believe donanemab can provide clinically meaningful benefits for people with this disease and the possibility of completing their course of treatment as early as six months once their amyloid plaque is cleared,” said Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience.

In early May, Lilly announced that donanemab met the primary and all cognitive and functional secondary endpoints in the Phase III study. Submission to the U.S. FDA for traditional approval was completed last quarter with regulatory action expected by the end of the year. Submissions to other global regulators are currently underway.

TRAILBLAZER-ALZ 2 enrolled participants with a broad range of cognitive scores and amyloid levels. Participants were stratified by their level of tau, a predictive biomarker for disease progression, into either a low-medium tau group (sometimes referred to as intermediate tau) or a high tau group. All participants were then assessed over 18 months using scales that measure both cognition and function, including the integrated Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

Among participants with low-medium levels of tau (n=1182), donanemab treatment significantly slowed decline by 35% on iADRS and 36% on CDR-SB. Among all amyloid-positive early symptomatic AD study participants (n=1736), treatment with donanemab significantly slowed decline by 22% on iADRS and 29% on CDR-SB.

Donanemab specifically targets deposited amyloid plaque and has been shown to lead to plaque clearance in treated patients. In this study, treatment with donanemab significantly reduced amyloid plaque levels regardless of baseline pathological stage of disease.

Among all participants, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo. Participants were able to stop taking donanemab once they achieved predefined criteria of amyloid plaque clearance. Approximately half of participants met this threshold at 12 months and approximately seven of every ten participants reached it at 18 months.

In 2021, Lilly announced and published in the New England Journal of Medicine (NEJM) results from the Phase II TRAILBLAZER-ALZ study. In addition, Lilly shared data from TRAILBLAZER-ALZ 4, the first active comparator study in early symptomatic Alzheimer’s disease, at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference in 2022.

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, which is focused on preventing symptomatic Alzheimer’s disease in participants with preclinical AD; TRAILBLAZER-ALZ 5, a registration trial for early symptomatic Alzheimer’s disease currently enrolling in China; and TRAILBLAZER-ALZ 6, which is focused on expanding our understanding of ARIA through novel MRI sequences, blood-based biomarkers, and different dosing regimens of donanemab.

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