A uniQure gene therapy slowed progression of Huntington’s disease by 75% after three years, statistically significant clinical trial results the company says will support plans for a regulatory submission next year. If approved, the gene therapy would become the first treatment for this progressive neurodegenerative disorder.
The uniQure gene therapy, AMT-130, is not a cure for Huntington’s. But the results reported Wednesday indicate disease-modifying effects along with a manageable safety profile — benchmarks that have eluded many drug research efforts in this rare disease.
Huntington’s stems from mutations to the gene that codes for huntingin, a protein important for neuronal function. The buildup of mutant huntingin in the brain damages and kills neurons. Disease symptoms include involuntary muscle movements as well as cognitive and behavioral changes. According to Amsterdam-based uniQure, an estimated 75,000 people in the U.S. and Europe have Huntington’s.
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AMT-130 uses an engineered virus to deliver to brain cells micro RNA designed to silence the huntingin gene and a highly toxic protein fragment. The one-time treatment is administered in a surgical procedure that delivers the gene therapy into the diseased areas of the brain.
UniQure evaluated its Huntington’s gene therapy in an open-label Phase 1/2 study that enrolled 29 patients; 17 received the high dose and 12 received the low dose. The main goal was to measure disease progression at 36 months according to a widely used rating scale that’s a composite of several different assessments of Huntington’s symptoms. This composite measure was compared to an external control group drawn from a natural history study. Last year, uniQure reached agreement with the FDA that this comparison, under a prespecified statistical analysis plan, may serve as the basis for a regulatory submission.
The 75% slowing in disease progression result at 36 months was for 12 patients in the high-dose group with a data cutoff of June 30. These patients also achieved a 60% reduction in disease progression at 36 months measured by total function capacity, a different rating scale. This measure was a secondary goal of the pivotal study. Furthermore, UniQure reported an average 8.2% reduction in neurofilament light protein, a protein whose presence is thought to be indicative of neurodegeneration. For context, a Huntington’s patient would be expected to see a 30% to 45% increase in this protein over three years, Dr. Sarah Tabrizi, professor of clinical neurology and director of the University College London Huntington’s Disease Center, said during a uniQure conference call to discuss the results.
“To me, this suggests that AMT-130’s targeting of mutant huntingin and all its toxic forms is indeed preserving nerve cells and in turn, neurological function,” said Tabrizi, who was a consultant on uniQure’s studies. “I have over 30 years of experience in Huntington’s disease research and clinical care, and I believe these data are the first to provide clear evidence of an investigational therapy inducing Huntington’s disease modification.”
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UniQure said AMT-130 was generally well tolerated by patients and had a manageable safety profile for both doses. The most common adverse effects reported in the study included headache as well as pain associated with the procedure.
The new results for AMT-130 were consistent with an interim data readout last year, when uniQure released data showing an 80% slowing of disease progression and statistically significant lowering of NfL levels in the blood in 21 patients with up to 24 months of follow up.
In a note sent to investors, Leerink Partners analyst Joseph Schwartz said the latest results exceeded expectations. While total function capacity has historically been the FDA’s favored clinical trial goal in Huntington’s, this endpoint has been considered too difficult to show a change in patients with early stage disease — like the patients that uniQure enrolled — and within the timeframe of a clinical trial. But the results show improvement in all measures, including the composite score. That makes this dataset stronger, particularly in the key areas of function and cognition, which matter most to patients, Schwartz said.
“A key question we repeatedly heard going into this readout was, ‘at what point will the data be enough for other investors to care?’” Schwartz said. “We think the wait is over: these data look pretty definitive to us and actually exceed what we thought was reasonable to expect.”
UniQure plans a fourth quarter 2025 meeting with the FDA to discuss the AMT-130 trial results. If all goes well, uniQure expects to file a biologics license application in the first quarter of next year. The company will ask for priority review, which could lead to a regulatory decision in six months.
Shares of uniQure opened Wednesday at $39.20 each, nearly triple Tuesday’s closing price. After releasing the AMT-130 trial results, uniQure made some financial moves to support potential commercialization of the Huntington’s gene therapy. The company extended the term of its $50 million in debt financing to 2030 and secured up to $125 million in additional non-dilutive financing.
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