Novel Gene Therapy Significantly Slows Progression of Huntington Disease

The phase 1/2 clinical trial (NCT04120493) of AMT-130 (uniQure) for the treatment of patients with Huntington disease has met its prespecified primary end point, with a high dose of the gene therapy candidate demonstrating statistically significant slowing of disease progression at 36 months compared with a propensity score-matched external control.^1,2

The news, according to a news release from uniQure, offers a possible treatment pathway for patients with this condition that causes degeneration in cognition, behavior, and physical movement.^1,2

Huntington disease is an inherited neurodegenerative disorder. It can lead to severe motor symptoms, including chorea, behavioral abnormalities, and cognitive decline. There remain no approved therapies that can delay the onset or slow the progression of Huntington disease, necessitating continued research into possible paradigm-shifting treatments. Gene therapies present a possibly curative avenue for these patients, allowing for personalized and targeted care.¹

Part of uniQure’s clinical program of AMT-130, the multi-center, dose-escalating phase 1/2 trial aimed to elucidate the safety, tolerability, and exploratory efficacy signals of the medication for the treatment of Huntington disease. A total of 26 individuals with early manifest Huntington disease were randomized to receive either a low dose (n = 6), high dose (n = 10), or an imitation procedure (n = 10). AMT-130 was administered through a single MRI-guided, convection enhanced stereotactic neurosurgical delivery method.¹

According to topline 36-month efficacy results for patients receiving high-dose AMT-130 as of June 30, 2025, a statistically significant slowing of disease progression—as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS)—of 75% (P = .003) was observed, meeting the trial’s primary end point. Patients treated with AMT-130 had a mean change in cUHDRS from baseline of –0.38 compared with a change of –1.52 for patients in the propensity score-matched external control, according to the investigators.¹

Meeting a key secondary end point, there was a statistically significant 60% slowing of disease progression as measured by the Total Functional Capacity (TFC) score at 36 months. Treated individuals had a mean change in TFC from baseline of –0.36 compared with –0.88 for propensity matched patients.¹

A series of positive trends in other secondary end point measures of motor and cognitive function, including Symbol Digit Modalities Test (SDMT), Stroop. Word Reading Test (SWRT), and Total Motor Score (TMS). Specifically, there was an 88% slowing of disease progression as measured by SDMT; a 113% slowing of disease progression according to SWRT; and a 59% slowing of progression measured by TMS.¹

Safety was manageable and ell-tolerated across both doses of AMT-130, and as of the cut-off date, there had been no novel drug-related, serious adverse events observed in 3 years. Common adverse events in the treatment groups were related to the administration procedure and were all resolved, the investigator’s reported. The favorable results garnered from the high-dose group indicate a dose-dependent response to AMT-130, a critical observation that can help guide future treatment strategies and management protocols.¹

It is important for pharmacists to remain attune to the clinical development of AMT-130. If research indicators remain positive, AMT-130 is on a solid path to future FDA approval, at which it could become a paradigm-shifting medication for patients with Huntington’s disease. Pharmacists should learn how the treatment is prepared and administered while ensuring that patients know about possible, easily-treatable adverse effects.¹

“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,” Sarah Tabrizi, MD, FRCP, FRS, FMedSci, PhD, professor of clinical neurology and director of the University College London Hunting’s Disease Center, said in the news release. “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.”¹

REFERENCES

1. uniQure. uniQure announces positive topline results from pivotal phase 1/II study of AMT-130 in patients with Huntington’s disease. News Release. Released September 24, 2025. Accessed September 30, 2025. https://www.uniqure.com/investors-media/press-releases

2. Safety and proof-of-concept (POC) study with AMT-130 in adults with early manifest Huntington’s disease. ClinicalTrials.gov Identifier: NCT04120493. Last Updated September 5, 2025. Accessed September 30, 2025. https://clinicaltrials.gov/study/NCT04120493