Alnylam Pharmaceuticals has reported preliminary results from an ongoing Phase Ib clinical study assessing its investigational ribonucleic acid interference (RNAi) candidate, brezosiran (ALN-HTT02), in adult patients with Huntington’s disease (HD).
The preliminary data were presented during oral and poster sessions at the European Huntington’s Disease Network Clinical Research Congress 2026 in Krakow, Poland.
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The trial is designed to assess single ascending intrathecal brezosiran doses in adult patients aged 25 to 70 years with genetically confirmed HD classified as HD-ISS Stage 2 or early Stage 3.
Across five completed cohorts comprising 48 enrolled participants, the therapy generated dose-dependent decline in mutant protein levels, confirmed using two separate assays.
Patients in the highest dosage cohort tested so far recorded an average mutant protein drop of 60% to 64% from baseline at month 3, with an individual peak reduction reaching 83%. A sixth cohort consisting of 12 participants is actively recruiting.
Over monitoring periods lasting up to 12 months, researchers noted no dose-dependent gains in ventricular brain volume, neurofilament light chain levels, or inflammatory markers in cerebrospinal fluid.
The longevity of the response indicates that twice-yearly administration may be feasible in subsequent development programmes.
Following the primary phase, eligible subjects can join an open-label extension to receive intrathecal injections once every six months for up to 36 months, facilitating the assessment of long-term safety, sustained target engagement, and exploratory disease progression metrics.
Alnylam chief research and development officer Pushkal Garg said: “The deep and durable mutant huntingtin lowering observed after a single dose, together with the encouraging safety profile seen to date, give us confidence to advance brezosiran into a pivotal study.
“We plan to evaluate our differentiated huntingtin-lowering approach in a rigorous placebo-controlled study to determine whether it can alter the course of HD.
“We are deeply grateful to the people living with Huntington’s disease, their families and caregivers, advocacy organisations, investigators and clinical trial staff whose partnership makes this work possible.”
Subject to regulatory alignment, Alnylam plans to launch a placebo-controlled pivotal study in 2027 to assess whether the therapy slows disease progression.
The ongoing randomised, double-blind, placebo-controlled study is running across clinical sites in the UK, Germany, and Canada.
Brezosiran uses the company’s C16 conjugate platform to deliver treatment directly to the central nervous system and is developed alongside Regeneron Pharmaceuticals.
HD is a fatal, inherited neurodegenerative condition triggered by an expanded cytosine-adenine-guanine (CAG) repeat in exon 1 of the huntingtin gene.
Brezosiran has not received safety or efficacy clearance from the US Food and Drug Administration or any other health authority.
In September 2025, Alnylam disclosed new analysis findings from the HELIOS-B Phase III clinical trial of RNAi therapeutic Amvuttra (vutrisiran) for adults with cardiomyopathy caused by wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM).
