uniQure N.V. (NASDAQ: QURE) has announced that the U.S. Food and Drug Administration (FDA) has agreed to key elements of an Accelerated Approval pathway for AMT-130, the company's investigational gene therapy for Huntington's disease. This agreement paves the way for a potential expedited route to market for what could be a transformative therapy for this devastating neurodegenerative disorder.
FDA Alignment on Accelerated Approval
Following a Type B meeting in November, the FDA has indicated that data from uniQure's ongoing Phase I/II studies, when compared to a natural history external control, may serve as the primary basis for a Biologics License Application (BLA) under the Accelerated Approval pathway. This decision eliminates the need for an additional pre-submission study, potentially saving significant time and resources in the drug development process.
Walid Abi-Saab, M.D., chief medical officer of uniQure, stated, "Our alignment reflects the strength of our data and collaborative discussions with the staff and senior management at FDA’s Center for Biologics Evaluation and Research (CBER). This is an important milestone for the Huntington’s disease community as it puts us on the most rapid and efficient pathway to deliver a potentially life-changing therapy."
cUHDRS as a Clinical Endpoint
The FDA has also agreed that the composite Unified Huntington’s Disease Rating Scale (cUHDRS) may be used as an intermediate clinical endpoint for Accelerated Approval. The cUHDRS is a comprehensive assessment tool that measures motor function, cognitive abilities, and behavioral aspects of Huntington's disease, providing a holistic view of disease progression.
Neurofilament Light Chain (NfL) as Supportive Evidence
In addition to cUHDRS, the FDA has indicated that reductions in neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) may serve as supportive evidence of therapeutic benefit in the application for accelerated approval. NfL is a biomarker of neurodegeneration, and its reduction suggests a potential slowing of neuronal damage.
Clinical Trial Data
uniQure is currently conducting two multi-center, dose-escalating, Phase I/II clinical studies to evaluate the safety, tolerability, and exploratory efficacy signals of AMT-130. The U.S. study (NCT04120493) involves 26 patients with early manifest Huntington’s disease, while the European study (NCT05243017) has enrolled 13 patients. A third cohort is enrolling an additional 12 patients across sites in the U.S. and EU to explore the therapy in combination with immunosuppression.
Interim data presented in July 2024 showed durable, dose-dependent slowing of disease progression based on the cUHDRS of treated patients compared to a propensity-weighted natural history. These data also showed reductions in CSF NfL, a measure of neurodegeneration, in treated patients at 24 months compared to baseline. Specifically, the high-dose cohort had an 80% slowing in disease progression versus external controls (P = .007), while the low-dose cohort showed a non-statistically significant 30% slowing (P = .21).
Huntington's Disease: An Unmet Need
Huntington’s disease is a rare, inherited neurodegenerative disorder affecting approximately 70,000 people in the U.S. and Europe. It leads to motor symptoms, behavioral abnormalities, and cognitive decline, with no currently approved therapies to delay onset or slow progression. AMT-130 represents a potential breakthrough in addressing this unmet medical need.
Next Steps
uniQure has initiated BLA readiness activities and plans to engage further with the FDA in the first half of 2025 to discuss its statistical analysis plan and technical CMC (chemistry, manufacturing, and controls) requirements.
Financial Implications
The announcement of the FDA agreement led to a surge in uniQure's stock price, reflecting investor optimism about the potential for AMT-130 to reach the market sooner than expected. Stifel analyst Paul Matteis described the alignment as a "best-case scenario" for uniQure, given low expectations for an accelerated approval path.
