- 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
Oct 23, 2026--CAMBRIDGE, Mass.--(BUSINESS WIRE)-- 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.”
All eligible Phase 1b study participants have the option to transition into a Ph1b open-label extension (OLE) study, receiving brezosiran once every six months for up to 36 months to evaluate long-term safety, sustained target engagement, and exploratory measures of disease progression. Alnylam plans to initiate a placebo-controlled pivotal study in 2027, pending regulatory alignment, to evaluate the ability of brezosiran to slow disease progression in adults with Huntington’s disease.
“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.”
Brezosiran and the Phase 1b results will be featured as part of Alnylam’s 10th “RNAi Roundtable” series on October 26, 2026, at 10:00 a.m. ET. To register for the webcast or access replay details, please visit the Events and Presentations section of the Alnylam website at investors.alnylam.com.
To view Alnylam’s EHDN Clinical Research Congress 2026 presentations, please visit Capella.
About the Phase 1b Study of Brezosiran (ALN-HTT02)
The Phase 1b trial is a randomized, double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of brezosiran (ALN-HTT02). The ongoing study includes adult patients aged 25 to 70 years with genetically confirmed Huntington’s disease in HD-ISS Stage 2 or early Stage 3. Reported data include a total of 48 enrolled participants across five single-dose cohorts with doses increasing by no more than 3x when escalating to the next cohort (with an additional Dose 6 cohort (N=12) currently enrolling and yet to be evaluated). The Phase 1b single ascending dose (SAD) study is focused on assessing safety and tolerability as well as target engagement (HTT-lowering). The Phase 1b study is ongoing in Canada, Germany, and the United Kingdom, with patients receiving brezosiran every 6 months in the open-label extension (OLE).
About Brezosiran (ALN-HTT02)
Brezosiran (ALN-HTT02) is an investigational, intrathecally administered RNAi therapeutic in development for the treatment of Huntington’s disease (HD), which utilizes Alnylam’s proprietary C16 conjugate platform for delivery to the central nervous system. Brezosiran targets exon 1 of the huntingtin (HTT) mRNA transcript — a differentiated targeting strategy designed to reduce the production of all forms of the huntingtin protein, including full-length mutant HTT and the shorter mutant HTT1a, both of which may be important contributors to disease progression. This program is being developed by Alnylam in collaboration with Regeneron Pharmaceuticals. The safety and efficacy of brezosiran have not been evaluated or established by the U.S. Food and Drug Administration or any other health authority.
About Huntington’s Disease
Huntington’s disease (HD) is an autosomal dominant, progressively fatal neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin (HTT) gene. The accumulation of toxic mutant huntingtin proteins drives disease progression, resulting in widespread neuronal loss, motor dysfunction, cognitive decline, and psychiatric symptoms. HD typically presents in adults aged 30 to 50 and relentlessly progresses over 15 to 20 years. More than one hundred thousand individuals are living with symptomatic disease globally, with many gene-positive individuals and family members and caregivers impacted. There are currently no approved disease-modifying therapies capable of slowing, halting, or reversing HD progression.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that has become an important and clinically validated platform for drug development. Its discovery was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing RNAi, Alnylam pioneered a new class of medicines known as RNAi therapeutics. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. RNAi therapeutics have been used to treat hundreds of thousands of patients worldwide, demonstrating the impact of this approach across rare and common diseases.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt, or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health.