ALPHA-1062 Approved for Alzheimer Disease, GLP-1 Agonist Shows Neuroprotective Effects Against Dementia, Lecanemab 3-Year Data Reported

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to an announcement, the FDA has approved Alpha Cognition’s ALPHA-1062 (Zunveyl), a prodrug of an approved AChE inhibitor, galantamine, as a treatment for patients with mild-to-moderate Alzheimer disease (AD). ALPHA-1062, a delayed-release oral tablet formulation, is considered a new-generation AChEI inhibitor, with expected minimal gastrointestinal adverse events. The approval was based on results from 4 studies demonstrating the bioequivalence of ALPHA-1062 to galantamine and galantamine extended-release (ER). Across those studies, only 2% of treated patients had AEs from treatment, with no cases of insomnia observed. ALPHA-1062 is absorbed in the small intestine as an insert drug. Binding with AChE in the gastrointestinal nervous system is blocked by the addition of a benzyl ester to galantamine.

Newly reported research from a phase 2b study showed that treatment with liraglutide (Novo Nordisk), a glucagon-like peptide 1 (GLP-1) receptor agonist, has neuroprotective effects against Alzheimer disease (AD) dementia. Presented at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1 in Philadelphia, Pennsylvania, these findings highlight the potential of GLP-1 analogues in the treatment of AD. The study, a multicenter, randomized, double-blind, placebo-controlled trial, featured 204 patients with AD from 7 cohorts in the UK who were treated with either liraglutide or placebo as a daily subcutaneous injection for 12 months. At the conclusion of the treatment period, results on MRI showed a slower decline of temporal lobe volume and total grey matter volume in liraglutide-treated patients relative to those on placebo.

At the 2024 Alzheimer’s Association International Conference (AAIC)is, held July 28-August 1 in Philadelphia, Pennsylvania, Eisai presented new 3-year data from an open-label extension (OLE) of its pivotal phase 3 Clarity AD trial (NCT03887455) highlighting lecanemab (Leqembi), an FDA-approved therapy for early-stage Alzheimer disease (AD). At 3 years, investigators observed a continued clinically and personally meaningful benefit among treated patients, with continued positive impacts on biomarkers after plaque removal. In total, 95% of patients who completed the 18-month core study chose to continue in the OLE, where they continued on lecanemab treatment for up to 3 years. Over 3 years of treatment across the core study and OLE, lecanemab reduced cognitive decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) by –0.95 compared with the expected decline based on those in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) group. For context, a change of –0.45 (P = .00005) was observed between lecanemab and placebo at the 18-month mark of the core study.

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