uniQure claims latest interim data shows gene therapy can slow Huntington’s disease

The clinical journey for uniQure’s Huntington’s disease gene therapy got off to a bumpy start, but now the company says the latest interim data shows a slowing of disease progression. 

The latest readout covers 24-month follow up data for 21 patients with the neurodegenerative disease who received one of two doses of the gene therapy AMT-130 across a pair of phase 1/2 trials in the U.S. and Europe.

The data showed a mean 0.2 point reduction in a Huntington’s disease rating scale for patients who received the higher dose of AMT-130, compared to a 1 point reduction across a propensity-weighted external control group of 154 patients. This equated to an 80% slowing of disease progression.

Meanwhile, the lower dose group saw a 0.7 reduction in their score, representing a 30% slowing of disease progression, the biotech said. These data demonstrated “statistically significant, dose-dependent, and durable evidence of potential therapeutic benefit,” uniQure said in a July 9 release.

Mean cerebrospinal fluid levels of neurofilament light protein—a well-known biomarker of neurodegeneration—were down 11% compared to baseline across all patients who received AMT-130.

The gene therapy continues to be generally well-tolerated, with a manageable safety profile at both doses, the company added. There were no new treatment-related serious adverse events reported.

“We believe this is the first clinical trial of any investigational medicine for Huntington’s disease to show evidence of a potential long-term clinical benefit and reduction of a key marker of neurodegeneration,” uniQure’s Chief Medical Officer Walid A bi-Saab, M.D., said in the release.

“Moreover, given the one-time administration of AMT-130, we are in a unique position to continue accumulating longer-term patient outcomes from the phase 1/2 studies to support the emerging therapeutic benefit,” Abi-Saab added. 

Huntington’s is a rare inherited disease that causes the progressive degeneration of nerve cells in the brain, leading to impairment of physical abilities, movement, thinking and psychiatric disorders. Treatments are available to manage symptoms but there is currently no disease-altering therapy available.

The clinical signals coming out of the AMT-130 trials have slowly become more positive over recent months. But things got off to a rocky start in 2022 when the therapy was scrutinized after safety signals prompted a pause in dosing for two groups in an open-label, European phase 1/2 trial. The pause, which was recommended by a safety monitoring board after three patients were hospitalized with various symptoms, was lifted in November 2022.

The earliest disease data was later deemed “noisy and difficult to interpret,” but interim findings in December 2023 received a warmer reception. Even at that point, the principal investigator was only willing to say that efficacy signals were “on the favorable side.”

Now, observers are more confident to point to AMT-130’s potential, with Victor Sung, M.D., professor of neurology at the University of Alabama at Birmingham, using today’s release to claim the 24-month results “are exciting and provide compelling evidence of potential therapeutic benefit.”

“The preservation of motor and cognitive function observed through two years, combined with reduced NfL levels below baseline, defy expectations about the natural progression of Huntington’s disease,” Sung added in this morning’s release.

Investors also seemed pleased with the latest slice of data, sending uniQure’s stock up 26% to $4.76 in pre-market trading on Tuesday from a Monday closing price of $3.78.

uniQure reiterated this morning that it plans to meet with the FDA in the second half of the year to discuss the potential for expedited clinical development.