Huntington Disease Gene Therapy AMT-130 Completes Trial Enrollment


A sister study of AMT-130 in Europe dosed its first patients in February.

uniQure has completed patient enrollment of the first 2 cohorts in its phase 1/2 clinical trial (NCT04120493) of AMT-130, a gene therapy for the potential treatment of early manifest Huntington disease (HD).1

“We are very pleased to have completed the enrollment of the first 26 patients in this ongoing clinical trial,” Ricardo Dolmetsch, PhD, president, research and development, said in a statement.1 “It’s a major milestone for the trial and an important achievement for our clinical operations team. Our investigators have done an exceptional job in enrolling this important study.”

AMT-130 is a recombinant, adeno-associated virus (AAV) vector 5 gene therapy that consists of a DNA cassette encoding a microRNA that lowers Huntingtin protein. The ongoing, randomized, sham-controlled, double-blind trial is evaluating the safety and tolerability of AMT-130 as well as proof –ofconcept in patients with early manifest HD. A blinded 12-month period will be followed by a 5-year, unblinded long-term follow-up period. Patients are treated with a single administration of AMT-130 using MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum.

The first cohort enrolled consists of 10 patients randomized to AMT-130 treatment (n = 6) or sham procedure (n = 4). The second cohort consists of 16 patients randomized to AMT-103 treatment (n = 10) or sham procedure (n = 6). The study will also enroll a third cohort that will explore the use of an alternative stereotactic navigation system to simplify placement of infusion catheters, with a planned enrolment of up to 18 participants.

READ MORE: Proposed FDA Gene Editing Guidance Emphasizes Long-Term Safety Evaluations

“We look forward to providing a clinical update in the second quarter of this year from the 12-month interim analysis of the 10 patients in the first cohort, including safety, mutant HTT protein (mHTT) and neurofilament light chain (NfL) data. We also remain on track with the enrollment of our European open-label clinical trial of AMT-130,” Dolmetsch added.1 

AMT-130 is developed using uniQure’s proprietary miQURE microRNA platform and is the first clinical-stage candidate developed with the platform. miQURE is designed to spread through an organ viz exosomes and degrade mRNA produced by pathologic genes without causing toxicity. 

A sister, phase 1b/2 study of AMT-130 is also being run in Europe. This study plans to enroll 15 participants across 2 dose cohorts, the first of which were dosed in February 2022.

“We are very pleased to expand the clinical development of AMT-130 and to build on our ongoing experience in the Phase I/II clinical trial in the United States,” Dolmetsch said in a statement at that time.2 “We expect to complete patient enrollment in this European study by the end of the year and to provide safety and target-engagement data from the full 10-patient, low-dose cohort in the US trial in the second quarter of this year.”

Huntington disease presents an area of high unmet need, as there are currently no disease-modifying treatments available. The community was devastated after Roche, who was developing a promising antisense oligonucleotide, tominersen, halted the phase 3 GENERATION HD1 study in March 2021 after a report from an Independent Data Monitoring Committee suggested that the drug’s risk/benefit profile was not in favor of patients.3 In January 2022, Roche announced that after a post-hoc analysis revealed a possible benefit for younger patients with less disease burden, they will be launching a new phase 2 trial of the drug.4 

Other gene therapy ventures from Voyager Therapeutics and Sanofi Genzyme have since been sidelined, while Spark Therapeutics recently announced a new partnership to help develop a gene therapy for the disease.

1. uniQure Announces Completion of Patient Enrollment in the First Two Cohorts of its Phase I/II Clinical Trial of AMT-130 for the Treatment of Huntington’s Disease. News release. Unyque. March 21, 2022.
2. uniQure Announces Dosing of First Patients in European Open-Label Clinical Trial of AMT-130 Gene Therapy in Huntington’s Disease. News release. UniQure. February 7, 2022.
3. Roche provides update on tominersen program in manifest Huntington’s disease. News release. Roche. March 22, 2021.
4. Ionis' partner to evaluate tominersen for Huntington's disease in new Phase 2 trial. News release. Ionis. January 18, 2022.
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