UniQure’s Huntington’s Gene Therapy Slowing Decline at Four Years

Rare Daily Staff

UniQure said that its experimental gene therapy AMT-130 for the rare neurodegenerative condition Huntington’s disease continued to slow the disease’s progression four years after a single treatment.

The results come from phase 1/2 studies with a data cutoff of June 30, 2026. Twenty-nine patients have been treated in the studies’ first two cohorts: 17 at a high dose and 12 at a low dose. UniQure compared their outcomes with a matched group of people from ENROLL-HD, a natural history dataset. That group is known as an external control.

Huntington’s disease leads to motor symptoms including chorea, behavioral abnormalities and cognitive decline resulting in progressive physical and mental deterioration. The disease is an autosomal dominant condition with a disease-causing CAG repeat expansion in the first exon of the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain. There are currently no approved therapies to delay the onset or to slow the disease’s progression.

Huntington’s disease is caused by a mutation in the HTT gene. It typically appears in mid-adulthood and leads to progressive loss of motor control, cognitive decline, and psychiatric symptoms. There are no approved treatments that can halt or reverse the underlying course of the disease, and patients often face a gradual loss of independence over 10 to 20 years.

AMT-130 is designed as a one-time gene therapy delivered directly to the brain using an adeno-associated virus vector. The treatment aims to silence the mutant huntingtin gene that drives the disease process, with the goal of slowing or preventing neuronal damage. It has FDA Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Fast Track designations.

At 36 months, the company now has data on 15 high-dose patients, up from 12 in a September 2025 analysis. UniQure reported that the therapy slowed progression by 80 percent on the composite Unified Huntington’s Disease Rating Scale (cUHDRS), a combined measure of movement, thinking and function. On Total Functional Capacity (TFC), which tracks the ability to work, manage finances and handle daily self-care, the reported slowing was 67 percent.

At 48 months, in 12 high-dose patients, the picture was mixed. On the primary endpoint of cUHDRS, the study showed 44 percent slowing. That result was not statistically significant. TFC showed 61 percent slowing. Treated patients’ TFC score fell by 0.37 points on average, versus 0.94 points in the control group.

The company also compared the two doses at 48 months. High-dose patients declined less than low-dose patients on both measures, which UniQure said is consistent with a dose-dependent effect.

UniQure argues the 48-month benefit is understated. It said 53 percent of data were missing in the updated control group at 48 months. It also said people who dropped out of follow-up were progressing faster than those who stayed, which would make the remaining controls look healthier.

UniQure described the therapy as generally well tolerated. The most common side effects were tied to the administration procedure, and all have resolved. As previously disclosed, five high-dose participants (17 percent) had serious side effects involving inflammation of the central nervous system, and all fully resolved.

One low-dose patient died by suicide about five years after treatment. The study investigator assessed the death as unrelated to treatment. The company noted that suicide and suicidal thoughts occur at substantially elevated rates in Huntington’s and are among the disease’s leading causes of death.

At a June 2026 meeting, the U.S. Food and Drug Administration told UniQure that 36-month data from 12 high-dose patients would be acceptable as the primary basis for an application for marketing approval under the accelerated approval pathway. These news results were not part of the application the company submitted.

Victor Sung, a neurologist who directs the University of Alabama at Birmingham’s Huntington’s Disease Clinic, said the control group’s decline slowed in a way that doesn’t match the disease’s typical course. “Huntington’s disease does not slow on its own; the biology is one of inevitable progressive decline,” he said. “Seeing that treatment difference maintained at four years is meaningful for people living with this relentlessly progressive degenerative disease.”