Two Companies Advance Novel Therapies for Huntington's Disease

Two pharmaceutical companies are advancing distinct therapeutic approaches for Huntington's disease, with the U.S. Food and Drug Administration agreeing to support an accelerated approval filing for one gene therapy while a UK biotech selects a novel candidate for another. The developments signal progress in a field with currently no approved disease-modifying therapies.

The FDA has agreed that existing trial data could support an accelerated-approval filing for uniQure's Huntington's treatment, sending the Dutch drugmaker's U.S.-listed shares up more than 70% in premarket trading. The decision represents a significant reversal, as FDA officials had indicated late last year that available data was insufficient to support a filing, with one senior regulator describing the company's gene therapy, AMT-130, as a "failed product."

Data from an early-to-mid-stage trial published last year showed patients who received a high dose of AMT-130 saw a 75% reduction in disease progression in a three-year analysis, based on a widely used clinical scale. The FDA has now told the company that the three-year analysis would be sufficient as the main basis for a marketing application. The agency has also agreed to work with uniQure to finalize the design of a required confirmatory study before the filing, including using patients on standard treatment as a comparison instead of a sham procedure. uniQure plans to submit its application in the third quarter of 2026.

The accelerated approval pathway is designed to speed up access to treatments for serious conditions with no good alternatives. Huntington's disease is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain, leading to movement, cognitive and psychiatric problems.

Separately, UK biotech company Harness Therapeutics has selected HRN001 as its lead experimental treatment candidate for Huntington's disease. The therapy works by increasing levels of FAN1, a DNA repair protein shown to help prevent further expansion of Huntington's-causing CAG repeats in nerve cells—a process called somatic expansion. By precisely increasing FAN1, a target with compelling genetic validation in delaying disease onset, HRN001 represents a differentiated, first-in-class therapeutic approach.

Harness plans to continue preclinical development of the therapy this year, with the goal of moving HRN001 into clinical testing next year. The company has assembled a clinical advisory board of experts to guide the therapy's development.

Huntington's is caused by a trinucleotide repeat expansion mutation in the HTT gene. While this gene typically includes 10 to 35 repeats of a trio of DNA building blocks—a cytosine, an adenine, and a guanine—people with Huntington's have an excess number of CAG repeats. This results in the production of a longer-than-normal version of the huntingtin protein that is toxic to nerve cells. Increasing evidence shows that these repeats can grow longer over time in the nerve cells most affected by the disease, a process thought to play a key role in initiation and progression.

HRN001 specifically targets the FAN1 gene's messenger RNA, an intermediary molecule derived from DNA that is used as a template for protein production. The therapy was designed using the company's proprietary MISBA platform, which enables a precise, self-limited increase in FAN1 mRNA levels, thereby preventing excessive FAN1 overproduction that could be damaging. In preclinical models of Huntington's, HRN001 treatment has led to a strong increase in FAN1 levels and a reduction in somatic expansion, according to the company.