uniQure has announced positive topline data from the pivotal Phase I/II study of AMT-130 for the treatment of Huntington’s disease.
The study demonstrated that high-dose AMT-130 showed a statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) at 36 months compared with a propensity score-matched external control.
The study also met a key secondary endpoint by achieving a statistically significant slowing of disease progression as measured by Total Functional Capacity (TFC) at 36 months compared to a propensity score-matched external control.
Huntington’s disease is a rare, inherited neurodegenerative disorder that leads to motor symptoms including chorea, behavioural abnormalities and cognitive decline, resulting in progressive physical and mental deterioration.
The disease is an autosomal dominant condition caused by a disease-causing CAG repeat expansion in the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain.
Approximately 75,000 people have Huntington’s disease in the US, EU and the UK, with hundreds of thousands of others at risk of inheriting the disease.
Despite the clear aetiology of Huntington’s disease, there are currently no approved therapies to delay the onset or to slow the disease’s progression.
Trial results
The trial saw 29 patients with the disease receive either a low or a high dose of the gene therapy, named AMT-130.
The positive data comes from 12 patients who received the high dose and were evaluated at the 36-month mark, with the outcomes compared to a natural history data set.
The 36-month data revealed a statistically significant 75% reduction in disease progression amongst patients treated with the higher dose of AMT-130.
On average, these patients showed a 0.38-point decline on the Unified Huntington’s Disease Rating Scale, compared with a 1.52-point decline in the historical control group.
“I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists," said Sarah Tabrizi, director of the University College London Huntington’s Disease Centre and joint head of the department of neurodegenerative disease.
"These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.”
With the phase 1/2 results in hand, uniQure Chief Medical Officer Walid Abi-Saab, MD, said the company is eager to review the data in a meeting anticipated later this year, to submit a Biologics License Application (BLA) in the first quarter of 2026.
The company aims to bring AMT-130 to market next year.
“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease,” stated Walid Abi-Saab, chief medical officer of uniQure.
“These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders."
"Today’s outcome reflects the tireless commitment of so many at uniQure and I want to extend my deep gratitude to the team, as well as to the investigators, site personnel, patients and families who made this possible."
"We are eager to discuss the data with the FDA at our pre-BLA meeting expected later this year, with the goal of submitting a BLA in the first quarter of 2026.”
AMT-130 has been granted Breakthrough Therapy designation and Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA.
Hope for the future
The first effective treatment of Huntington's could encourage more people at risk to undergo testing and even influence family planning.
It also signals new hope for treatments for other genetic disorders.
UK genomics expert, Neil Ward, who is currently VP EMEA for genomic sequencing firm PacBio, said: "Until now, there has been no viable treatment for Huntington's, which meant many at-risk individuals weren’t offered testing or chose not to pursue it, even with a family history of the disease."
"This breakthrough could change that by giving people a reason to seek testing and even inform family planning. It also shows what could soon be possible for other devastating genetic disorders."
"Huntington’s is just one of a wider group of ‘repeat expansion disorders’, caused by stretches of repeated DNA that can disrupt how genes work."
"While Huntington’s is relatively straightforward to study, many other conditions have been out of reach for research and testing."
"This is because the repeats are too long or numerous for older genomic technologies and require multiple tests that were not practical for resource-pressured national health systems."
"Advances in sequencing technology now make it possible to study and diagnose these conditions in a single test, opening the door to more timely diagnoses and, ultimately, new therapies that could change lives across many families."
"For example, Wave Therapeutics in the UK is running clinical trials looking at expansions in a gene called C9orf72, which can cause conditions such as ALS or frontotemporal dementia.”
The news signals hope for the future of Huntington’s treatment, after a bit of a bumpy road marked by trial setbacks and company withdrawals.
What appeared to be a positive Phase II result for PTC Therapeutics’ Novartis-partnered candidate in May still knocked 20% off the biotech’s stock amid doubts about the path to accelerated approval.
Back in November 2024, Bayer abandoned work on its own clinical-stage gene therapy for the disease.
Pridopidine, which had shown promise in Phase II trials, hit a roadblock in July of this year when the EMA rejected it for marketing authorisation, citing disappointing clinical data.
However, other companies, such as Skyhawk, have restored hope in research into potential treatments, with their Phase I clinical trial of SKY-051 reducing levels of the mutant huntingtin (mHTT) protein in patients and as well as being well-tolerated.
As more promising data emerge, the field is beginning to shift from disappointment toward genuine optimism for patients and families affected by Huntington’s.