An experimental Huntington’s disease drug lowered a disease-linked protein by up to 83 percent after a single dose, drug maker Alnylam Pharmaceuticals said after presenting early trial results. The drug, brezosiran (ALN-HTT02), is an RNA interference therapy given by injection into the spinal canal, designed to lower the mutant huntingtin protein that drives the inherited neurological disorder.
Results from the ongoing Phase 1b study were presented on October 23 at the European Huntington’s Disease Network Clinical Research Congress 2026 in Krakow, Poland. Across the first five dose groups, reductions in mutant huntingtin protein in cerebrospinal fluid rose with the dose. In the highest dose group studied so far, the average fall from baseline was 60 to 64 percent at month 3, measured with two independent tests.
How brezosiran works
Brezosiran is a small interfering RNA therapy aimed at exon 1 of the huntingtin gene. It is designed to lower all forms of the huntingtin protein, including the full-length mutant protein and the shorter mutant HTT1a fragment, which a growing body of evidence suggests may play a role in how Huntington’s disease progresses. Huntington’s disease is an inherited condition that causes the progressive breakdown of nerve cells in the brain, affecting movement, thinking and mood, and there are still no approved treatments that change its course.
The Phase 1b study is randomized, double-blind and placebo-controlled, testing single ascending doses in adults with Huntington’s disease. Data reported so far cover 48 participants across five single-dose cohorts, while a sixth cohort of 12 participants is still enrolling. The trial, registered as NCT06585449, has sites in Canada, Germany and the United Kingdom and an estimated total enrollment of 66 participants aged 25 to 70.
Brezosiran works by silencing the gene that produces huntingtin, using a short strand of RNA that targets the gene’s message before the protein can be made. Because the therapy is given directly into the spinal canal, it reaches the fluid that bathes the brain and spinal cord. Alnylam, based in Cambridge, Massachusetts, has built its work on this RNA interference approach across several diseases, and brezosiran is its candidate for Huntington’s disease. The Phase 1b study tests whether lowering the protein in spinal fluid is safe and how long the effect lasts after one injection.
Huntington’s disease is caused by a faulty gene passed from parent to child, and each child of an affected parent has a 50 percent chance of inheriting it. Symptoms typically appear in adulthood and worsen over time, affecting movement, memory and mood. No treatment yet approved changes the course of the disease, so current care focuses on managing symptoms. That gap is why a therapy that lowers the mutant protein itself has drawn close attention from patient groups and researchers, even at this early stage.
Brezosiran safety results so far
Some participants have been followed for up to 12 months after treatment. Alnylam said the early safety and tolerability profile was encouraging, with no dose-dependent increases in cerebrospinal fluid inflammatory markers, neurofilament light chain levels or brain ventricular volume. Those three measures are used to watch for possible neurological injury or other treatment-related changes.
Dr. 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 on the study, said the results were a promising advance for the program. “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,” he said.
Brezosiran larger trial planned for 2027
The durability of the protein lowering suggests brezosiran could be given just twice a year in later development, Alnylam said. A placebo-controlled late-stage study is planned for 2027, pending alignment with regulators. The company stressed that the data so far cover a biomarker and safety, and they do not show that the drug slows the disease itself. That question will fall to the larger trial now being planned.