Safety Board Recommends AMT-130 Trial Continue Enrolling, Treating Patients

No significant safety concerns associated with AMT-130, uniQure’s experimental gene therapy for Huntington’s disease, were identified in the first two patients participating in a Phase 1/2 trial assessing the treatment’s safety, tolerability, and efficacy.

These were the main conclusions that came out of the first meeting of an independent Data Safety Monitoring Board (DSMB), which is currently overseeing the trial (NCT04120493). During this first meeting, the DSMB reviewed and analyzed three-month safety data from the first two patients who were dosed in the study, including one who received AMT-130 and the other a sham surgery (control group).

Since no safety signals that could prevent further dosing were identified, the DSMB deemed it would be safe to enroll and treat the next two patients in the trial.

“We are very pleased with the positive outcome from this first DSMB meeting,” Ricardo Dolmetsch, president of research and development at uniQure, said in a press release. “We will now advance the study and expect to enroll the next two patients as soon as possible.”

AMT-130 is a gene therapy that aims to lower the production of a mutated form of the huntingtin protein, the underlying cause of Huntington’s disease.  This therapy is composed of a small portion of synthetic genetic material — called microRNA (miRNA) — that is inserted into cells and carried using an adeno-associated virus (AAV), which has been modified to be harmless.

Once inside a cell, the miRNA targets the RNA molecule that carries instructions to produce the huntingtin protein, and marks it for degradation. In this way, the therapy lowers the production of abnormal huntingtin protein.

This five-year Phase 1/2 trial is evaluating the safety and proof of concept of AMT-130 in up to 26 patients with early Huntington’s disease. During the early stage of Huntington’s, which begins at diagnosis and lasts for approximately eight years, the patient is fully functional at home and at work.

The study, currently recruiting participants at several sites across the U.S., comprises two phases. The first, a one-year period, will focus on assessing the safety and potential impact of AMT-130 on disease progression. The second, four-year phase will gather long-term safety data from patients treated with AMT-130, as well as information on the therapy’s potential effects on disease progression.

Some trial participants will be randomly assigned to receive one of two doses of AMT-130, which will be given through a surgical procedure called MRI-guided convention-enhanced delivery (CED). That procedure allows the therapy to be directly administered to the patients’ striatum — a brain region responsible for movement control. Others will be assigned to undergo a sham surgery (control group).

In addition to safety and tolerability, the trial will assess the effects of AMT-130 on the levels of mutant huntingtin and other disease biomarkers in the cerebrospinal fluid, which is the liquid that circulates in the brain and spinal cord. Disease severity and patients’ motor and cognitive abilities also will be assessed.

AMT-130 was named an orphan drug in 2017 and given fast track designation in 2019 by the U.S. Food and Drug Administration. The European Medicines Agency also granted the therapy the designation of orphan medicinal product in 2018.