CAMBRIDGE, Mass. — October 23, 2026
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced positive initial Phase 1b results for brezosiran (ALN-HTT02), an investigational RNA interference (RNAi) therapeutic being developed for Huntington’s disease (HD). The findings showed dose-dependent reductions in mutant huntingtin protein (mHTT) in cerebrospinal fluid (CSF), with a mean reduction of 60% to 64% at Month 3 in the highest dose group evaluated to date and an individual reduction of up to 83%. The data were presented at the European Huntington’s Disease Network (EHDN) Clinical Research Congress 2026 in Kraków, Poland. According to Alnylam, target engagement was demonstrated using two independent assays, and reductions in mHTT were observed across the first five dose cohorts. Initial follow-up data include participants monitored for up to 12 months, with an encouraging safety and tolerability profile reported to date. The findings support the company’s plans to advance brezosiran into a placebo-controlled pivotal study in 2027, pending regulatory alignment. However, the Phase 1b study remains ongoing, and the treatment’s ability to slow disease progression has not yet been established.
Phase 1b Study Shows Durable Target Engagement
The ongoing Phase 1b trial is a randomized, double-blind, placebo-controlled, single-ascending-dose study evaluating brezosiran’s safety, tolerability, pharmacokinetics and pharmacodynamics. It has enrolled 48 adult participants across five single-dose cohorts, with an additional Dose 6 cohort of 12 participants currently enrolling and not yet evaluated. Participants are between 25 and 70 years old and have genetically confirmed Huntington’s disease in HD-ISS Stage 2 or early Stage 3. The initial findings indicate that brezosiran produced dose-dependent reductions in CSF mHTT following a single intrathecal dose. Alnylam reported that the durability of the observed reductions could support a potential twice-yearly dosing schedule in later development. The company also reported no dose-dependent increases in CSF inflammatory markers, CSF neurofilament light chain (NfL) or brain ventricular volume in the available data. Eligible participants can transition into an open-label extension (OLE) study, receiving brezosiran every six months for up to 36 months. The extension is designed to evaluate long-term safety, sustained target engagement and exploratory measures of disease progression. The Phase 1b program is being conducted in Canada, Germany and the United Kingdom. Neurologist Dr. Blair R. Leavitt, a principal investigator in the study, described the combination of huntingtin reduction and the observed safety profile as encouraging, while emphasizing the need for therapies that address disease progression.
Differentiated RNAi Approach Targets Multiple HTT Forms
Brezosiran is an investigational RNAi therapeutic administered intrathecally and uses Alnylam’s proprietary C16 conjugate platform for delivery to the central nervous system. It targets exon 1 of the huntingtin (HTT) messenger RNA transcript, with the aim of reducing production of multiple forms of huntingtin protein. This includes full-length mutant huntingtin and the shorter mutant HTT1a form, which may contribute to disease progression. According to the company, this targeting strategy is designed to address both forms rather than focusing solely on full-length mutant huntingtin. Alnylam is developing brezosiran in collaboration with Regeneron Pharmaceuticals. Pushkal Garg, M.D., Alnylam’s Chief Research and Development Officer, said the depth and durability of mHTT lowering observed after a single dose, alongside the safety findings reported so far, support advancing the program toward a pivotal study. The planned study is intended to rigorously assess whether brezosiran can slow disease progression in adults with Huntington’s disease. The current findings primarily demonstrate target engagement and provide initial safety information; they do not establish a clinical benefit or confirm that the therapy alters the course of the disease.
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Pivotal Study Planned for 2027 as Alnylam Prepares Webcast
Alnylam plans to initiate a placebo-controlled pivotal study in 2027, subject to regulatory alignment, to evaluate brezosiran’s potential to slow disease progression in adults with Huntington’s disease. The company will also feature the program and Phase 1b results during its 10th RNAi Roundtable webcast on October 26, 2026, at 10:00 a.m. Eastern Time. Registration and replay information will be available through the Events and Presentations section of Alnylam’s investor website. Huntington’s disease is an inherited, progressive neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It can lead to motor dysfunction, cognitive decline and psychiatric symptoms, and the disease progressively affects daily functioning. Alnylam noted that there are currently no approved disease-modifying therapies capable of slowing, halting or reversing HD progression. While the initial brezosiran data provide evidence of sustained biological activity and an encouraging early safety profile, additional clinical evaluation will be required to determine whether these effects translate into meaningful outcomes for patients. The safety and efficacy of brezosiran have not been established by the U.S. Food and Drug Administration or any other health authority.
Source: Alnylam Pharmaceuticals release
