Rare Daily Staff

UniQure reported that a small, low-dose cohort of patients in an ongoing phase 1/2 clinical trial its experimental Huntington’s disease gene therapy AMT-130 at 12 months achieved a mean 53.8 percent reduction from baseline in mutant HTT protein, a key biomarker of the deadly neurodegenerative disease.

The results involved four treated patients with evaluable data. The reductions ranged from 44 percent to 71 percent. In all, six of 10 patients were treated the AMT-130 in the randomized, blinded trial while four received a sham procedure. The company expects to present full results from the study next year.

Huntington’s disease is a rare, inherited disorder that leads to motor symptoms, including chorea, and 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. Despite the clear etiology of Huntington’s disease, there are no currently approved therapies to delay the onset or to slow the disease’s progression.

AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene using the company’s miQURE silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT).

The 10 patients enrolled in the low-dose cohort were all clinically diagnosed with early-stage Huntington’s disease with CAG repeats between 40-44, baseline Total Functional Capacity scores of 10-13, and Total Motor Scores of 7-23. Four patients were male and six were female with ages ranging from 34-58 years old. Demographics of the six treated patients were generally consistent with the four control patients.

AMT-130 was generally well-tolerated in treated patients at the lower dose. There were no serious adverse events related to AMT-130 reported in these patients. Two serious adverse events unrelated to AMT-130 occurred: a deep-vein thrombosis in the elbow in one patient that resolved with anticoagulants and transient post-operative delirium in a second patient that was resolved through supportive care.

Measurements of CSF NfL, a key biomarker of neuronal damage, increased as expected following the AMT-130 surgical procedure and approached baseline at 12 months. Two of the six treated patients were at or below baseline at 12 months with an additional patient below baseline at 15 and 18 months.

All 26 patients have been enrolled in the U.S. clinical trial, including the 10 patients in the low-dose cohort and 16 patients in the high-dose cohort. In the open-label European trial, all 6 patients in the low-dose cohort and four of nine patients in the high-dose cohort have received AMT-130.

“We have made excellent progress in our clinical investigation of AMT-130 and now have a total of 36 patients enrolled across our two phase 1/2 clinical studies in the U.S. and Europe,” said Matt Kapusta, CEO of UniQure. “Enrollment in the high-dose cohort of our open-label European study is well underway and is expected to be completed by the end of this year.”

Photo: Matt Kapusta, CEO of UniQure

X