Mivelsiran - (APPlauDS)

July 15, 2026: Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) reported multiple neuroscience R&D milestones presented at AAIC 2026.

Mivelsiran (APP-targeting RNAi; in development for CAA and Alzheimer’s disease):

• Initiated the global Phase 2 APPlauDS study in Down syndrome–associated Alzheimer’s disease (DS-AD). The trial will recruit people with Down syndrome and early-stage AD across ~30 sites globally; rationale is APP-lowering to reduce amyloid accumulation driven by trisomy 21.
• Presented updated Phase 1 safety/biomarker data in early-onset Alzheimer’s disease: safety analyses across single and multiple doses showed no evidence of increased ARIA risk. Reported durable CSF biomarker reductions with up to 30 months exposure; mean maximum reductions at the highest dose were -89.9% (sAPPβ) and -70.2% (Aβ42). Most common AEs were procedural pain/headache; no serious or severe AEs were deemed related to study drug.
• Announced completion of enrollment in the Phase 2 cAPPricorn-1 study in cerebral amyloid angiopathy (CAA). Primary endpoint is rate of new lobar microbleeds by MRI; initial results are expected in 2028.

ALN-5288 (MAPT/tau-targeting RNAi; Alzheimer’s disease/tauopathies):

• Shared preclinical data and the design of an ongoing first-in-human Phase 1 trial (NCT07214727), initiated in Q4 2025, in collaboration with Regeneron Pharmaceuticals.