The Year in Alzheimer Disease: Disease-Modifying Therapies, Regulatory Approvals, and Safety

The year 2025 was a dynamic and transformative one for the management of Alzheimer disease (AD), marked by progress in regulatory approval and long-term efficacy validation, but by significant clinical trial setbacks as well. In this quick look back at the developments this year, Patient Care highlights the acceleration of disease-modifying therapies (DMTs), particularly focusing on anti-amyloid antibodies and novel oral agents.

Pipeline activity was consistent throughtout the year, with the FDA granting Fast Track designation to several emerging therapies, including a novel AD antibody from Merck and tau-targeting agents like anti-MTBR Tau antibody BMS-986446 and etalanetug. There were positive outcomes for oral agents as well. Blarcamesine, an orally available small-molecule activator of the sigma-1 receptor, was associated with cognitive decline comparable to prodromal aging, and ALZ-801 (valiltramiprosate), an orally administered prodrug of tramiprosate that slowed brain atrophy specifically in individuals homozygous for APOE4. The were some disappointing phase 3 readouts, however, notably the inability of the glucagon-like peptide-1 receptor agonsit semaglutide to slow AD progression, and the failure of J&J's anti-tau drug posdinemab to meet its primary endpoint.

A signficant milestone was the FDA approval of the subcutaneous autoinjector for lecanemab (Leqembi; Eisai) for maintenance therapy in early AD, signaling a step toward easier at-home administration. At about the same time, donanemab was authorized in Europe, supported by data showing sustained cognitive benefits over 3 years and reduced risk of serious ARIA through revised dosing schedules.

Following in chronological order is a selection of the top news covered by Patient Care this year in drug research and development and regulatory achievements in the rapidly expanding area of AD and related dementias.

Alzheimer Disease: New Brain Targets and the New Drug Pipeline Among 180+ active AD trials, 15 biological targets span traditional Aβ and tau proteins as well as new pathways in brain metabolism, neuroinflammation, and synaptic health.

Alzheimer's Drug Discovery Foundation Responds With Optimism to Disappointing Results from evoke Late Stage Trials. The phase 3 results offer key lessons for metabolic and inflammatory pathway targets, ADDF notes, highlighting biomarker findings that advance Alzheimer science.

Merck Secures Fast Track for Novel AD Antibody and Reports First-in-Human Data. New safety and biomarker results from MK-2214 and MK-1167 advance Merck’s dual approach to Alzheimer therapy.

J&J's Investigational Anti-Tau Alzheimer Drug Posdinemab Fails to Meet Primary Endpoint in Phase 2b Trial. J&J halts phase 2b AuTonomy trial after anti-tau antibody posdinemab fails to slow clinical decline, marking another setback for tau-targeting therapeutics.

Semaglutide Fails to Slow Progression of Alzheimer Disease Compared to Placebo: Novo Nordisk Phase 3 Trial Update. Evoke trials testing semaglutide for Alzheimer disease missed primary endpoint, failing to demonstrate benefit on cognition despite positive effects

Two Alzheimer Disease Therapies to Watch at CTAD 2025: Lecanemab and Sabirnetug Updates. Eisai and Acumen Therapeutics will present new data in areas including long-term outcomes, brain delivery strategies, and early-stage Alzheimer disease.

Axsome Submits sNDA for AXS-05 to Treat Agitation in Alzheimer Disease Submission of the sNDA suggests a potential FDA decision on the dextromethorphan-bupropion combination sometime during the first quarter of 2026.

Investigational Oral Agent ALZ-801 Slows Brain Atrophy and Cognitive Decline in APOE4 Homozygotes with Early AD Valiltramiprosate is a novel disease modifying therapy designed to inhibit formation of soluble neurotoxic amyloid oligomers, acting upstream in the in the amyloid cascade.

Plasma Biomarkers Achieve High Accuracy for Confirmatory Aβ Positivity in Eligibility Test for DMT in Alzheimer Disease Plasma assays combining p-tau217 and Aβ42/40 accurately confirm AD, supporting patient eligibility for anti-amyloid disease-modifying therapies.

FDA Grants Fast Track Designation to Anti-MTBR Tau Antibody BMS-986446 for Alzheimer Disease The FDA has granted fast track designation to BMS-986446, an anti–microtubule binding region tau antibody in phase 2 trials for early Alzheimer disease.

Emerging Tau-Targeting Antibody for Alzheimer Disease Receives FDA Fast Track Designation FDA grants Fast Track designation to etalanetug, a promising tau-targeting antibody for Alzheimer disease that could expand treatment options for the neurodegenerative disease.

Oral Blarcamesine Shows Marked Reduction in Cognitive Decline in Early Alzheimer Disease: Phase 2b/3 Data Once-daily blarcamesine was associated with minimal cognitive decline at 48 weeks, with changes comparable to those observed in prodromal aging.

FDA Approves Subcutaneous Leqembi Autoinjector for Maintenance Therapy in Early Alzheimer Disease The FDA has cleared Eisai and Biogen’s Leqembi Iqlik, the first at-home subcutaneous autoinjector for maintenance therapy in patients with early Alzheimer disease.

For the full year of Patient Care reporting on AD research and drug development, visit the Alzheimer Disease/Dementia Topic Resource Center