Cambridge, Mass. — Alnylam Pharmaceuticals, Inc. announced progress across several neuroscience programs at the Alzheimer’s Association International Conference 2026, including the launch of a Phase 2 study of mivelsiran in Down syndrome-associated Alzheimer’s disease.
The company also completed enrollment in a Phase 2 study of mivelsiran in cerebral amyloid angiopathy, presented updated Phase 1 data in early-onset Alzheimer’s disease and highlighted its tau-targeting investigational therapy ALN-5288.
Mivelsiran is an investigational RNA interference therapeutic designed to reduce production of amyloid precursor protein, or APP, which contributes to the formation of amyloid beta.
Alnylam has initiated the global Phase 2 APPlauDS study evaluating mivelsiran in people with Down syndrome and early-stage Alzheimer’s disease. The trial is expected to recruit participants at approximately 30 sites worldwide.
“People with Down syndrome have a genetically determined form of Alzheimer’s disease that is now the leading cause of death among adults over age 35 years,” said Michael S. Rafii, M.D., Ph.D., Professor of Neurology at the Keck School of Medicine of USC and presenting author. “APPlauDS is the first clinical trial to evaluate whether an RNAi approach can reduce APP overexpression caused by trisomy 21, where the APP gene is located. By lowering APP expression early in the disease process, this approach has the potential to slow or prevent the progression of Alzheimer’s disease in people with Down syndrome.”
The company also presented updated Phase 1 data from patients with early-onset Alzheimer’s disease who received single or multiple doses of mivelsiran.
The analysis found no evidence of an increased risk of amyloid-related imaging abnormalities, or ARIA. Mivelsiran produced sustained reductions in cerebrospinal fluid levels of soluble amyloid beta precursor protein and amyloid beta 42 during treatment exposure lasting up to 30 months.
In the highest-dose group, mean maximum reductions from baseline were 89.9% for soluble amyloid beta precursor protein and 70.2% for amyloid beta 42.
The most common adverse events were procedural pain and headache. No serious or severe adverse events were considered related to the study drug. Cerebrospinal fluid safety testing also showed no significant increases in total protein or white blood cells.
Alnylam separately completed enrollment in the Phase 2 cAPPricorn-1 study of mivelsiran in cerebral amyloid angiopathy, a condition characterized by the progressive accumulation of amyloid beta in the brain’s blood vessels and a leading cause of hemorrhagic stroke.
The study’s primary endpoint is the rate of new lobar microbleeds detected through magnetic resonance imaging. Initial results are expected in 2028.
Alnylam also presented preclinical findings and details of the ongoing Phase 1 study of ALN-5288, an investigational RNAi therapeutic targeting microtubule-associated protein tau. The program is being developed in collaboration with Regeneron Pharmaceuticals for Alzheimer’s disease and other tau-related disorders.
The first-in-human study began in the fourth quarter of 2025.
Alnylam currently has two RNAi therapies targeting Alzheimer’s disease in clinical development. Including programs conducted with Regeneron, the company has seven clinical-stage neuroscience programs.
“The updates we’re sharing at AAIC 2026 mark an important step forward for Alnylam as we continue to build our leadership in neuroscience,” said Toby Ferguson, M.D., Ph.D., Senior Vice President and Head of the Neuroscience Therapeutic Area at Alnylam. “Our RNAi platform is demonstrating strong potential across neurological diseases, with a favorable safety profile and the possibility to reach broad patient populations. By targeting disease-driving proteins like amyloid and tau at their genetic source, we aim to deliver the kind of transformative, disease-modifying therapies patients and families have long awaited.”
