Alnylam cuts mutant huntingtin protein 60–64% in preliminary Phase 1b data
Key Facts
Alnylam Pharmaceuticals announced positive preliminary Phase 1b results on October 23, 2026, for its investigational drug brezosiran, also known as ALN-HTT02, to treat Huntington’s disease. The company said the highest dose group evaluated recorded an average reduction of 60–64% in mutant huntingtin protein in cerebrospinal fluid after 3 months compared with baseline, while the largest individual reduction was 83%. Alnylam presented the data at the 2026 European Huntington’s Disease Network Clinical Research Congress in Krakow, Poland. It said the study focuses on safety, tolerability and proof that the drug targets the protein, objectives that differ from demonstrating an improvement in the course of the disease. The company said it plans a placebo-controlled pivotal study in 2027, subject to regulatory alignment, to assess whether the treatment slows Huntington’s disease progression.
The announced results included data from 48 participants across 5 single-dose groups, while enrollment of 12 participants in a sixth dose group was ongoing and that group had not been evaluated when the results were announced. The Phase 1b trial was designed as randomized, double-blind and placebo-controlled, allowing a single dose to be compared with a control group. Alnylam said the decline in mutant protein was dose-dependent and that target engagement was demonstrated using two independent assays. The study included adults aged 25 to 70 with a genetically confirmed diagnosis of the disease who were in Stage II or early Stage III according to the Huntington’s Disease Stages scale. These details provide context for the size of the preliminary data set and the scope of participants evaluated, while the sixth group remains outside the announced results.
The company said some participants in the preliminary data had been followed for up to 12 months and that it had observed no dose-related increases in cerebrospinal fluid inflammatory markers, neurofilament light chain protein or brain ventricular volume. It described safety and tolerability as encouraging, without these measures providing evidence that the disease had slowed clinically. It added that sustained reduction of mutant protein could allow the company to explore a twice-yearly dosing regimen in later development stages. That frequency remains a future development possibility, while the open-label extension study is evaluating administration once every 6 months for up to 36 months. That phase will track long-term safety, sustained protein target engagement and exploratory measures of disease progression.
Brezosiran targets exon 1 of the huntingtin gene messenger RNA and was designed to reduce both full-length mutant protein and the shorter HTT1a form. The treatment uses RNA interference technology, is administered into the cerebrospinal fluid, and is being developed by Alnylam in collaboration with Regeneron Pharmaceuticals. Alnylam said the treatment’s safety and efficacy have not been evaluated or established by the U.S. Food and Drug Administration or any other health authority. There are currently no approved disease-modifying treatments capable of slowing, stopping or reversing its progression, according to the company. In a separate earlier trial, Roche announced in March 2021 that it was stopping dosing of tominersen in the Phase 3 GENERATION HD1 study, following a recommendation from an independent data monitoring committee that assessed potential benefits and risks for participants. Roche said at the time that its data review had identified no new or emerging safety signals, and participants continued to be followed without receiving the drug or placebo.
Roche described Huntington’s disease as genetic, rare and progressive, and estimated that average survival after the onset of motor symptoms ranges from approximately 10 to 20 years. In Australia, the number of residents with the disease was estimated at about 2,400 in 2024, according to the Australian Institute of Health and Welfare; this is a local estimate. The institute said care focuses on symptom relief, support and quality of life, and that no treatments are available to slow or prevent the disease. At the treatment-program level, the protein-reduction results indicate that the biological target is being engaged, while measuring the treatment’s effect on disease progression requires a pivotal trial designed for that purpose. Alnylam is scheduled to discuss brezosiran and the Phase 1b results in a webcast on October 26, 2026, at 10:00 a.m. U.S. Eastern Time.