FDA asks uniQure for new controlled study for Huntington’s gene therapy AMT-130
The FDA said uniQure’s Phase I/II data for Huntington’s disease gene therapy AMT-130 are not adequate for a marketing application. The agency recommended a new randomised, double-blind, sham surgery-controlled study.
uniQure said the FDA does not consider the Phase I/II study data adequate to support a marketing application for the Huntington’s disease gene therapy ifezuntirgene inilparvovec, or AMT-130. In a Type A meeting earlier this month, the FDA recommended a prospective, randomised, double-blind, sham surgery-controlled study.
The company’s Huntington’s disease program consists of two Phase I/II trials. The U.S. study (NCT04120493) is double-blind sham-controlled in two cohorts, while the European study (NCT05243017) is open label.
In September 2025, a 75% slower progression of Huntington’s disease in 17 patients across both trials treated at the high dose of the therapy was reported at three years in comparison to the external control arm. The disease was not reversed.
The first trial of any gene therapy in Huntington’s was designed cautiously with safety in mind. The trial criteria outlined specific requirements for the striatal MRI volume per hemisphere, because it needed to be large enough for surgeons to inject the gene therapy, and patients had to meet a certain score on the Diagnostic Confidence Level scale used to indicate disease progression.
In 2018, the FDA insisted on a sham control for 12 months and then patients were rolled over to the treatment arm, while in Europe regulators said implementing a sham control would be unethical and there was no sham arm. The control arm in the study was a natural history study of 2,500 patients suitable for inclusion.
uniQure has said it will request a Type B meeting with the FDA in Q2 2026 to explore next steps. MRI-guided surgery necessary to deliver the gene therapy may not be possible in all countries, which could be a bottleneck for access.