Huntington Disease Gene Therapy AMT-130 Wins FDA Fast Track Designation


The planned phase 1/2 trial of the recombinant AAV5 vector treatment, the first one-time administered AAV gene therapy to enter clinical testing for Huntington disease, is expected to begin dosing patients in the second half of 2019.

Dr Bruce Bebo

Matt Kapusta, MBA, chief executive officer of uniQure

Matt Kapusta, MBA

The FDA has granted fast track designation to uniQure's AMT-130, a gene therapy candidate for the treatment of Huntington disease.

The drug is comprised of a recombinant AAV5 vector and carries a DNA cassette encoding a microRNA that non-selectively lowers, or knocks down, human huntingtin protein in Huntington disease, and targets the exon1 protein fragment.

“Achieving fast track designation from the FDA underscores the high unmet medical need for patients suffering from Huntington disease, for which there are currently no approved, disease-modifying treatments,” Matt Kapusta, MBA, chief executive officer, uniQure, said in a statement.1 “We are nearing the initiation of a phase 1/2 study of AMT-130, the first one-time administered AAV gene therapy to enter clinical testing for Huntington disease, and are on track to treat the first patient in the second half of 2019.”

The planned phase 1/2 dose-escalating study will assess the safety, tolerability, and efficacy of 1-time treatment of AMT-130 in patients with Huntington disease.

Data from 5 preclinical animal models show that a single administration of AMT-130 resulted in a dose-dependent and sustained reduction of mutant huntingtin protein in deep structures of the brain including the striatum, putamen, and cortex. After direct injection, AMT-130 was observed to spread to the cerebral cortex and lowered mutant huntingtin protein in frontal areas of the brain.2

In rodent trials, delivery of AMT-130 showed dose-dependent vector DNA and microRNA expression, up to 12-months of lowering of huntingtin protein, a reduction of huntingtin aggregation in the brain of rats, the prevention of neuronal dysfunction, and an improvement in Huntington disease-like symptoms and a median survival increase of 24%.3

The FDA completed a review of an investigational new drug application for AMT-1302 for Huntington disease in January 2019, which allowed uniQure to begin its planned phase 1/2 trial, and in October 2017, the FDA granted orphan drug designation to AMT-130 for the same indication.

In January 2018, the European Medicines Agency granted the therapy an orphan medicinal product designation for the same indication, which made it the first investigational AAV-gene therapy for Huntington disease to receive such designation.


1. uniQure Receives FDA Fast Track Designation for AMT-130 Gene Therapy for the Treatment of Huntington’s Disease [news release]. Lexington, Mass. and Amsterdam, the Netherlands: uniQure; April 8, 2019. Accessed April 8, 2019.

2. uniQure has demonstrated preclinical proof-of-concept and has submitted an IND in Huntington's disease. UniQure website. Accessed April 8, 2019.

3. Evers M. Establishing preclinical proof-of-concept of gene therapy for Huntington disease. Presented at: American Academy of Neurology 2018 Annual Meeting; Los Angeles, CA; April 21 to 27, 2018. Accessed April 8, 2019.

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