Alnylam Announces Positive Initial Phase 1b Data for Brezosiran (ALN-HTT02) Demonstrating Deep and Durable Huntingtin Lowering in Huntington’s Disease
- Initial Phase 1b results show mean reduction of cerebrospinal fluid mutant huntingtin of 60 to 64% at month 3 with individual reduction of up to 83% and encouraging safety and tolerability with potential for twice yearly dosing -
- Unique targeting approach reduces both mutant huntingtin and shorter mutant HTT1a-
- Placebo-controlled pivotal study planned for 2027, pending regulatory alignment -
- Alnylam to discuss Huntington's disease program at October 26 RNAi Roundtable -
CAMBRIDGE, Mass., October 23, 2026--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported positive initial Phase 1b clinical trial results for ALN-HTT02, an investigational RNAi therapeutic in development for the treatment of Huntington's disease, which will be developed under the International Nonproprietary Name (INN) brezosiran (bre-ZOH-sir-an). The data were presented in oral and poster presentations at the European Huntington's Disease Network (EHDN) Clinical Research Congress 2026 in Krakow, Poland.
In the ongoing Phase 1b study, participants on single ascending intrathecal doses of brezosiran experienced robust, dose-dependent reductions of mutant huntingtin protein (mHTT) in cerebrospinal fluid (CSF), with target engagement demonstrated using two independent assays. Across the first five cohorts, dose-dependent reductions of CSF mHTT were observed, with a mean reduction from baseline of 60-64% at month 3 in the highest dose group evaluated to date, with a maximum individual reduction of 83%. The observed durability of mHTT-lowering shows the potential for a twice-yearly dosing paradigm in downstream development. The initial data include individuals followed for up to 12 months, during which an encouraging safety and tolerability profile has been observed with no dose-dependent increases in CSF inflammatory markers, CSF neurofilament light chain (NfL) or brain ventricular volume.
"The evidence suggesting that brezosiran has the potential to achieve robust and durable HTT-lowering, while maintaining an encouraging safety profile, is a very promising advance for this program at a time when there are still no approved disease-modifying therapies for Huntington disease," said Dr. Blair R. Leavitt, MDCM, FRCPC, neurologist and Director of Research at the Centre for Huntington Disease at the University of British Columbia Hospital and a principal investigator on the Phase 1b study. "Brezosiran is designed to lower all forms of HTT, including full-length mutant HTT and the shorter mutant HTT1a, which a growing body of evidence suggests may play a key role in the progression of Huntington disease."