A uniQure gene therapy for Huntington’s disease has interim clinical data showing an 80% slowing of disease progression. An accelerated approval pathway is one of the topics the company wants to discuss with the FDA.

By Frank Vinluan on July 09, 2024A uniQure gene therapy for Huntington’s disease has interim data showing the one-time treatment slows progression of this rare neurodegenerative disorder that has no FDA-approved therapies. Based on these encouraging data, the company said Tuesday it now plans to discuss with regulators the potential for a faster clinical and regulatory path forward.
Huntington’s stems from a genetic mutation that leads to abnormal versions of the huntingin protein. The disease leads to motor dysfunction, behavioral changes, and cognitive decline. The uniQure gene therapy, code-named AMT-130, uses an engineered virus to deliver microRNA that silences the huntingin gene and the toxic protein fragment that drives the disease.
Amsterdam-based UniQure is evaluating AMT-130 in a sham-controlled Phase 1/2 sham clinical trial in the U.S. and Europe. After a blinded 12-month period, study participants will be followed unblinded for five years. The studies are intended to determine which dose of AMT-130 to advance to pivotal testing.
The interim results announced Tuesday are from up to 24 months of follow-up in 21 treated patients. A total of 12 patients received the low dose and nine received the high dose as of the March 31 cutoff date. Using a composite scale used to assess Huntington’s progression, these patients were compared with an external control developed using data from natural history studies.
According to uniQure, results so far show a statistically significant 80% slowing of disease progression in patients who received the high dose; 30% slowing of disease progression in those given the low dose. UniQure said the high dose group showed stability of motor and cognitive function that was near baseline levels throughout the 24 months of follow-up.
Another goal of the study is measuring cerebral spinal fluid levels of neurofilament light protein (NfL), proteins that are thought to be an indicator of neurodegenerative disease. There’s precedent for using NfL levels as a biomarker in neurological disease clinical trials. Qalsody, an amyotrophic lateral sclerosis drug developed by Biogen, received accelerated FDA approval last year based in part on clinical data indicating a lowering of NfL levels in the blood. In the AMT-130 study, uniQure reported a statistically significant lowering of NfL levels compared to baseline. To date, the gene therapy has been well tolerated by patients with no reports of serious adverse events.
“These updated results are exciting and provide compelling evidence of potential therapeutic benefit,” Dr. Victor Sung, professor of neurology at the University of Alabama at Birmingham (UAB), and director of the UAB Huntington’s Disease Clinic, said in a prepared statement. “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.”
Based on these interim data, uniQure said it plans to meet with the FDA later this year to discuss expedited clinical development of the therapy, including a potential pathway for accelerated approval. In a note sent to investors last week, William Blair analyst Sami Corwin wrote that FDA feedback on the regulatory path for AMT-130 is key, as it will provide clarity on the viability of an accelerated approval. This pathway could use surrogate biomarkers such as measures of NfL. UniQure also needs to hear whether the agency’s Center for Biologics Evaluation and Research (CBER) will require a placebo-controlled clinical trial or if a natural history or external comparator arm will suffice as a control.
“Recent commentary from Peter Marks, M.D., Ph.D., the director of CBER, indicates that the division will look to increasingly use accelerated approval pathways and more flexible pivot trial designs for gene therapies, which we believe could be a tailwind for uniQure as it begins regulatory discussions from AMT-130,” Corwin said.
UniQure said a third cohort in the U.S. portion of the Phase 1/2 study is expected to complete enrollment in the second half of this year. This group is evaluating the gene therapy in combination with immunosuppression. UniQure anticipates safety data from this group will be ready in the first half of next year. By mid-2025, uniQure anticipates presenting another interim analysis from the Phase 1/2 trial, this time with 36 months of data.
Investors welcomed the interim results. Shares of uniQure soared more than 70% in trading on Tuesday.
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