CAMBRIDGE, Mass. — Alnylam Pharmaceuticals announced positive initial results from a Phase 1b clinical trial of brezosiran (ALN-HTT02), an investigational RNA interference (RNAi) therapy for Huntington’s disease, demonstrating substantial and sustained reductions in a protein associated with the progressive neurological disorder.
The findings, presented at the European Huntington’s Disease Network Clinical Research Congress 2026 in Krakow, Poland, showed that patients receiving a single dose of brezosiran experienced significant reductions in mutant huntingtin protein, which plays a central role in the development and progression of Huntington’s disease.
According to Alnylam, patients in the highest dose group evaluated to date achieved an average reduction of 60% to 64% in mutant huntingtin levels in cerebrospinal fluid three months after treatment. Individual patients experienced reductions of up to 83%.
The ongoing study is evaluating increasing doses of brezosiran administered through an injection into the spinal canal. Researchers observed dose-dependent reductions in mutant huntingtin protein across the first five patient groups, with results confirmed using two independent testing methods.
The company said the durability of the treatment’s effects suggests that brezosiran could potentially be administered just twice a year, reducing the frequency of treatment for patients.
Initial safety findings were also encouraging, with some participants followed for up to 12 months after treatment.
Researchers reported no dose-dependent increases in inflammatory markers in cerebrospinal fluid, neurofilament light chain levels or brain ventricular volume, measurements used to monitor potential neurological injury or other treatment-related changes.
Huntington’s disease is an inherited neurological disorder that causes progressive deterioration of nerve cells in the brain. The condition can lead to involuntary movements, cognitive decline and psychiatric symptoms. Although medications are available to manage certain symptoms, there are currently no approved treatments that modify the underlying progression of the disease.
“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 Blair R. Leavitt, a neurologist and director of research at the Centre for Huntington Disease at the University of British Columbia Hospital and a principal investigator in the 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,” Leavitt added.
Brezosiran uses RNA interference technology to reduce production of huntingtin protein, including both the full-length mutant protein and a shorter form known as HTT1a.
Alnylam said this approach could potentially address multiple forms of the abnormal protein believed to contribute to the disease.
Participants who complete the initial Phase 1b study and meet eligibility requirements may enroll in an open-label extension study, where they will receive brezosiran every six months for up to three years.
The extension study will assess long-term safety, sustained reductions in huntingtin protein and exploratory measures of disease progression.
Alnylam also plans to initiate a placebo-controlled pivotal clinical trial in 2027, subject to agreement with regulatory authorities. The study will evaluate whether reducing huntingtin protein levels can slow the progression of Huntington’s disease in adults.
“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,” said Pushkal Garg, M.D., chief research and development officer at Alnylam.
“We plan to evaluate our differentiated huntingtin-lowering approach in a rigorous placebo-controlled study to determine whether it can alter the course of Huntington’s disease. We are deeply grateful to the people living with Huntington’s disease, their families and caregivers, advocacy organizations, investigators and clinical trial staff whose partnership makes this work possible,” Garg added.
The company is scheduled to provide additional details about its Huntington’s disease development program during an RNAi Roundtable discussion on October 26.
Brezosiran remains investigational, and further clinical testing will be necessary to determine whether the observed reductions in mutant huntingtin protein translate into meaningful improvements in patient outcomes.
