Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, has reported positive initial Phase 1b clinical trial results for brezosiran. The investigational RNAi therapeutic, known as ALN-HTT02, targets Huntington’s disease. Alnylam will develop it under the International Nonproprietary Name (INN) brezosiran (bre-ZOH-sir-an). The company presented the data in oral and poster sessions at the European Huntington’s Disease Network (EHDN) Clinical Research Congress 2026 in Krakow, Poland.
In the ongoing Phase 1b study, participants were administered single ascending intrathecal doses of brezosiran. Therefore, they demonstrated potent dose-dependent reductions of the mutant huntingtin protein (mHTT) in the cerebrospinal fluid (CSF). Target engagement was confirmed in two independent assays. In the first five cohorts, the highest dose group tested to date showed a mean reduction from baseline of 60-64% at month 3. The maximum individual reduction was 83%.
Importantly, the drug’s distinctive mechanism not only reduces mutant huntingtin but also the shorter mutant HTT1a. In addition, the durability of mHTT lowering supports a twice-yearly dosing paradigm in later development.
The initial data include individuals followed for up to 12 months. During that time, researchers observed an encouraging safety and tolerability profile. Furthermore, they saw 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.”
Alnylam Plans a Pivotal Study for Huntington’s Disease in 2027
All eligible Phase 1b participants can move into an open-label extension (OLE) study. There, they will receive brezosiran once every six months for up to 36 months. The extension will evaluate long-term safety, sustained target engagement, and exploratory measures of disease progression.
Meanwhile, Alnylam plans to start a placebo-controlled pivotal study in 2027, pending regulatory alignment. The study will test whether brezosiran can 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.”
Additionally, Alnylam will feature brezosiran and the Phase 1b results at its 10th “RNAi Roundtable” on October 26, 2026, at 10:00 a.m. ET. Interested readers can register for the webcast or find replay details in the Events and Presentations section of investors.alnylam.com. Finally, the EHDN Clinical Research Congress 2026 presentations are available on Capella.
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News Source: Businesswire.com
