FDA Places Gene Therapy AMT-130 on Fast Track to Speed Development

The U.S. Food and Drug Administration (FDA) has given fast track designation to AMT-130, uniQure’s gene therapy candidate for the treatment of Huntington’s disease.

The designation helps to speed the development, testing, and review of therapies for serious diseases with high unmet medical need.

“Achieving Fast Track Designation from the FDA underscores the high unmet medical need for patients suffering from Huntington’s disease, for which there are currently no approved, disease-modifying treatments,” Matt Kapusta, chief executive officer of uniQure, said in a press release.

uniQure is now finalizing arrangements for the first human clinical trial for AMT-130, and patient enrollment is set to begin this year.

“We are nearing the initiation of a Phase I/II study of AMT-130, the first one-time administered AAV gene therapy to enter clinical testing for Huntington’s disease, and are on track to treat the first patient in the second half of 2019,” Kapusta said.

AMT-130 is an experimental gene therapy designed to block production of the mutated form of the huntingtin (HTT) protein, the underlying cause of Huntington’s disease. It consists of a small portion of synthetic genetic material, called microRNA (miRNA), which binds to the RNA messenger molecule carrying the genetic information needed to make the huntingtin protein, marking it for elimination. As a result, the gene therapy prevents the production of a faulty HTT protein.

AMT-130 is carried inside nerve cells via a noninfectious virus called an adeno-associated virus (AAV).

Preclinical data has shown encouraging results for AMT-130. In a mouse model of the disease, three months after AMT-130 was injected into the striatum — a brain region that controls movement — researchers detected significant levels of AMT-130 microRNA in the treated areas. Treatment also led to a marked reduction of the mutant HTT protein. Further analyses showed improvement in brain cell function and a partial reversal of volume loss in the hippocampus — a brain area involved in memory.

Using healthy mini pigs (an animal model used to study disease), researchers detected no antibodies against AMT-130’s viral vector in the animals’ cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. The presence of antibodies against AMT-130’s viral vector can lower its effectiveness. These results are seen as promising, as they suggest that AMT-130’s potential is not compromised when administered to the brain or spinal fluid.

In another study, researchers used high-resolution magnetic resonance imaging (MRI) scans of 20 Huntington’s patients to identify the path through which they could safely and efficiently deliver AMT-130 to the desired regions of the brain.