UniQure hoping to meet on AMT-130 with regulators in early 2024

Company now advancing Phase 1/2 trials in Huntington's in US and EU

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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With early data on AMT-130 for Huntington’s disease reportedly looking promising, uniQure said it’s planning to meet early next year with regulatory authorities to discuss the late-stage development of its gene therapy candidate.

By that time, more data on the ongoing Phase 1/2 clinical trials testing the therapy will be available, the company said in a new update.

In the past months, uniQure has continued to advance those two AMT-130 trials  — one in the U.S. (NCT04120493) and one in Europe (NCT05243017). Interim results from the U.S. study, shared earlier this year, demonstrated that use of the gene therapy safely preserved clinical function for up to two years relative to the natural history of the neurodegenerative disease.

“We believe that, collectively, the data suggest early and promising evidence of clinical benefit in patients treated with AMT-130 compared to a patient-matched natural history data set,” Matt Kapusta, CEO of uniQure, said in a company press release.

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New update on AMT-130 trials expected by end of year

Additional U.S. trial updates are expected later this year, and the company also plans to enroll an additional group of 10 patients who will receive AMT-130 in combination with immunosuppressive therapies.

Data from the European trial, which is now recruiting up to nine people with early Huntington’s for its second, high-dose group, also are anticipated by the end of the year.

“We look forward to providing another update in the fourth quarter of 2023 that will include data from our European study, as well as preparing for regulatory interactions in the first quarter of 2024 to discuss the data and potential late-stage development of AMT-130,” Kapusta said.

AMT-130 is designed to stop the production of the abnormal form of the huntingtin protein that toxically accumulates in people with Huntington’s. It is delivered via a one-time infusion directly into the striatum, a brain region that’s particularly affected in Huntington’s.

In the placebo-controlled U.S. trial, launched in 2019, 26 patients with early Huntington’s were randomly assigned to one of two groups: low dose or high dose.

The low-dose group consisted of six people given AMT-130 (6 trillion vector genomes) and four who received an imitation surgical procedure. The high-dose group, meanwhile, included 10 patients treated with AMT-130 (60 trillion vector genomes) and six given the sham procedure.

We look forward to providing another update in the fourth quarter of 2023 that will include data from our European study, as well as preparing for regulatory interactions in the first quarter of 2024 to discuss the data and potential late-stage development of AMT-130.

The most recent interim results, announced in June, concerned one-year follow-up data from the high-dose group and two-year data from the low-dose group. The findings indicated that the treatment, at either dose, was well tolerated with a manageable safety profile.

Importantly, clinical and motor function were preserved for up to two years with either dose of AMT-130 relative to a group of untreated early Huntington’s patients included in the observational TRACK-HD study.

These benefits were observed across standard Huntington’s clinical measures, including Total Motor Score, Total Functional Capacity, and the composite Unified Huntington’s Disease Rating Scale.

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uniQure now recruiting more patients for AMT-130 trials

Earlier analyses from the low-dose group had shown that levels of neurofilament light chain (NfL), a marker of nerve cell damage, had initially increased in the cerebrospinal fluid (CSF) following AMT-130 delivery, but declined to near pre-surgical levels after a year. The CSF is the liquid that surrounds the brain and spinal cord.

The more recent data indicated that CSF NfL levels had dropped below those at study’s start (baseline) after two years of treatment in the low-dose group and were declining toward baseline after a year in the high-dose group.

Mutant huntingtin levels in the CSF also were reduced for up to two years in the low-dose group, but one-year findings in the high-dose group were more variable.

Taken together, “these data show that patients treated with AMT-130 appear to have generally preserved clinical and motor function and neurofilament light chain (NfL) levels suggesting a stable to improving neurodegenerative profile,” Kapusta said.

Participants are continuing to be monitored for up to a total of five years. Expected updates due by the end of the year will concern 1.5-year data from the high-dose group and 2.5-year data from the low-dose group. Those updates will include safety, biomarker, and functional results.

Per the study’s design, eligible participants given the sham surgery can crossover and receive AMT-130 after a year of treatment. To date, four patients in the high-dose group have crossed over (three for the high dose and one for the low dose), whereas the remaining two were not eligible, according to uniQure.

All of these patients received a short course of immunosuppressive therapy with AMT-130 administration.

The third group that uniQure plans to enroll in the U.S. trial will include 10 Huntington’s patients. The goal is to determine the short-term safety of AMT-130 given in combination with immunosuppressive treatments at the time of the surgery.

The Phase 1/2 trial in Europe is similar to the U.S. trial, but all participants are receiving AMT-130. The low-dose group is fully enrolled with six participants, and the company expects to complete recruitment of the nine-patient, high-dose group in the coming months.

Enrollment in the trial’s high-dose group was voluntarily paused last year by uniQure after three of the 14 patients given the high dose of AMT-130 across both trials had experienced severe adverse reactions. Recruitment was resumed in November with new safety protocols in place.