An experimental drug for Huntington’s disease lowered the harmful protein behind the illness for months after a single injection, its maker Alnylam Pharmaceuticals reported on October 23, 20261. In the highest dose group tested so far, levels of the mutant huntingtin protein in spinal fluid fell by 60% to 64% on average three months after one dose, and by as much as 83% in one person1. The company called the early safety picture encouraging and plans a larger trial in 2027 to test whether the drug, called brezosiran, can actually slow the disease2.
The results were presented at the European Huntington’s Disease Network Clinical Research Congress in Krakow, Poland1. They have not yet been published in a peer-reviewed journal.
What happened
Huntington’s disease is an inherited brain disorder that causes movement problems, a decline in thinking and psychiatric symptoms2. It is caused by a genetic change that leads the body to make a faulty, or mutant, form of a protein called huntingtin2. Symptoms usually start between ages 30 and 50, and the disease progresses over 15 to 20 years2. There are no approved treatments that slow, stop or reverse it2.
Brezosiran, previously known by the code ALN-HTT02, uses RNA interference, a way of silencing a gene2. It targets messenger RNA, the copy of the instructions that cells use to build huntingtin, with the aim of turning down how much protein gets made3. It is given by spinal tap, an injection into the cerebrospinal fluid that surrounds the brain and spinal cord3.
The study is still running in Canada, Germany and the United Kingdom1. It is randomized and double-blind, meaning people were assigned by chance to the drug or a placebo (a dummy treatment), and neither they nor their doctors knew which they got1. The reported results cover 48 adults aged 25 to 70 with genetically confirmed Huntington’s, split into five groups that each got a single, increasingly higher dose1. All were at a stage where movement or thinking had measurably changed, but their ability to work and manage daily life was still largely intact or only starting to decline3. A sixth group of 12 people is now being enrolled2.
The evidence so far
The amount of mutant huntingtin that dropped grew with the dose, and the company measured it with two separate lab tests2. The 60% and 64% figures for the top dose reflect the two different tests4.
Alnylam said the effect lasted long enough that the drug might one day be given twice a year1. HDBuzz, a news site that explains Huntington’s research to patients and families, noted that longer-term data are needed to confirm this3.
On safety, some participants have been followed for up to 12 months2. The company reported no dose-linked increases in spinal fluid markers of inflammation, in neurofilament light chain (a marker of nerve-cell injury), or in the size of the brain’s fluid-filled spaces, called ventricles2. Four serious adverse events were reported, none considered related to the drug itself, and two were linked to the spinal injection procedure3.
Huntingtin is a normal protein with many important jobs in cells, and brezosiran lowers both the faulty and the regular forms, so researchers need to know that cutting it is safe3. Before the human study, Alnylam had shared data from monkeys suggesting that deep and lasting huntingtin lowering with the drug was tolerated after single and repeated injections5.
What it does not show yet
The findings show the drug reaches its biological target, but they do not show whether it can slow Huntington’s or help people keep their ability to move, think or manage daily activities2. Alnylam did not share any information on whether patients improved, because the follow-up was too short, analysts at Oppenheimer noted6.
There is a cautionary history. Analysts at Stifel pointed out that Roche’s drug tominersen also lowered mutant huntingtin in spinal fluid, but that did not translate into a benefit for patients6. Roche has since abandoned it6. HDBuzz also stressed that this is a relatively small, early study and that longer monitoring will be essential to confirm the safety findings3.
Why the shorter protein matters
One feature that sets brezosiran apart is where it hits. It targets a region of the huntingtin instructions called exon 1, which lets it lower both the full-length protein and a shorter mutant fragment known as HTT1a2. HTT1a is thought to be a driver of damage in people with Huntington’s3, and researchers are still investigating its role in how the disease progresses2.
The drug also uses Alnylam’s C16 technology, which attaches a small fat-like molecule to the RNA drug to help it get into and spread through cells in the brain and spinal cord3. Getting RNA medicines to their targets in the nervous system has been a hurdle, so delivery is an important part of the design3.
Who is behind it
Alnylam runs and pays for the study1, and the drug is being developed with Regeneron Pharmaceuticals2. The partnership was first signed in 2019 and is worth upward of $1 billion6. Business stakes are high: Alnylam had recently cut its revenue guidance, and analysts had flagged brezosiran as a possible morale booster6.
Dr. Blair Leavitt, a neurologist at the University of British Columbia and a principal investigator on the study, said in the company’s announcement:
“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.”1
Pushkal Garg, Alnylam’s head of research and development, told STAT: “We’re getting high levels of knockdown with good safety and tolerability, and so this is all very, very encouraging.”4
How it fits the field
Huntington’s is one of the hardest areas in drug development, with many failed treatments along the way6. STAT described brezosiran as the latest in a series of intriguing candidates for the fatal disease4. Another approach, uniQure’s gene therapy, was reported in September 2025 to slow the disease by 75% at three years; more recent data showed a 44% slowing at four years, and the company has filed for approval with the US Food and Drug Administration6.
Oppenheimer said the brezosiran results fell in its “best case scenario,” suggesting “best-in-class knockdown”6. Stifel called it promising proof-of-concept but said it would take more data before judging the program6.
What to watch next
- Results from the sixth dose group, with 12 more people, which has not yet been evaluated1.
- The extension study, where eligible participants can get brezosiran every six months for up to 36 months to track long-term safety, lasting protein lowering and early signs of effects on the disease2.
- A larger placebo-controlled trial in 2027, designed to test whether the drug slows Huntington’s and to provide evidence needed for approval, depending on agreement with regulators31.
Until that larger trial reads out, the key open question remains whether lowering the protein in spinal fluid translates into people living better or longer with Huntington’s.
