uniQure Receives Positive Recommendation from DSMB for Huntington Disease


AMT-130 is uniQure’s first clinical program focusing on the central nervous system incorporating its proprietary miQURE silencing technology platform.

Ricardo Dolmetsch, PhD

Ricardo Dolmetsch, PhD

uniQure announced that the independent Data Safety Monitoring Board (DSMB) overseeing its phase 1/2 clinical trial (NCT04120493) of AMT-130 for the treatment of Huntington disease (HD) found no significant safety concerns, clearing the final 6 patients in the first cohort for enrollment.1

The board reviewed the 6-month safety data from the first 2 enrolled patients and the 90-day safety data from the next 2 enrolled patients within the study. Following the positive recommendation, uniQure expects to achieve full patient enrollment in cohort 1 by mid-year 2021.

"We are encouraged with the positive recommendation to proceed with patient enrollment from this second DSMB meeting,” Ricardo Dolmetsch, PhD, president, research and development, uniQure, said in a statement. “We will now focus on enrolling the last six additional patients in the first cohort and look forward to sharing initial biomarker and imaging data towards the end of the year.”

To date, 2 patients have been treated with AMT-130, and 2 have received the imitation surgery. The company is expected to enroll 26 patients with early manifest HD split into a 10 patient, low-dose cohort followed by a 16 patient, higher-dose cohort randomized to either AMT-130 or sham surgery assess safety, tolerability, and efficacy signals in the HD treatment.

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Patients included in the trial will be evaluated for a 5-year stretch, which includes a 12-month blinded core study period followed by an unblinded long-term follow-up. Administration of AMT-130 will be done through magnetic resonance imaging (MRI)-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum.

The AMT-130 gene therapy product candidate consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingin gene, while also leveraging the company’s proprietary miQURE silencing technology. AMT-130 represents uniQure’s first clinical program focusing on the central nervous system (CNS) using the silencing technology platform.2

According to uniQure, the therapeutic goal of AMT-130 is to inhibit the product of the mutant huntingtin protein (mHTT). Using AAV vectors to deliver micro-RNA’s directly to the brain for non-selective knockdown of the huntingtin gene represents what the company describes as “a highly innovative and promising approach to treating Huntington’s disease.”

Results from 12-month follow-up data in a HD minipig model, the largest available animal model for the disease, were presented in February 2019. All told, the data showed that a single administration of AMT-130 resulted in a dose-dependent and sustained reduction of the mHTT in the deep structures of the brain.

These reductions were seen in the striatum and putamen, where HD is known to manifest, and the cortex. Following administration, the drug was observed to spread to the cerebral cortex and lowered mHTT in the frontal areas of the brain that show neuropathological changes later in the disease course.

AMT-130 has been granted orphan drug designation by the FDA and orphan medicinal product designation from the European Medicines Agency both for the treatment of HD, making it the first investigational AAV-gene therapy in HD to receive such designation. Furthermore, the FDA also granted fast track designation for the therapy in April 2019.

1. uniQure announces positive recommendation from Data Safety Monitoring Board of phase 1/2 clinical trial of AMT-130 for the treatment of Huntington’s disease. News release. uniQure. February 8, 2021. Accessed February 11, 2021. http://www.globenewswire.com/news-release/2021/02/08/2171245/0/en/uniQure-Announces-Positive-Recommendation-from-Data-Safety-Monitoring-Board-of-Phase-I-II-Clinical-Trial-of-AMT-130-for-the-Treatment-of-Huntington-s-Disease.html
2. Silencing the mutant huntingtin gene. uniQure. http://uniqure.com/gene-therapy/huntingtons-disease.php. Accessed February 11, 2021.
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