FDA Rejects uniQure's AMT-130 Approval Pathway for Huntington's Disease

uniQure's shares fell over 40% following the U.S. Food and Drug Administration's (FDA) rejection of its data package for AMT-130, a gene therapy aimed at treating Huntington's disease. The FDA determined that the data from uniQure's Phase 1/2 studies, which compared AMT-130 to an external control, were insufficient to support a marketing application. Instead, the agency recommended a prospective, randomized, double-blind, sham surgery-controlled study, significantly extending the timeline for potential approval.

Fierce BiotechThe road ahead for uniQure: FDA says more data needed for AMT-130 gene therapy – HDBuzzBioSpace

AMT-130 is designed to reduce levels of the huntingtin protein in the brain, utilizing an adeno-associated virus (AAV) to deliver microRNA directly into the striatum, a brain region affected by Huntington's disease. Previous studies indicated a statistically significant reduction in disease progression, leading to initial optimism about the therapy's potential. However, the FDA's recent feedback indicates a shift in its stance, highlighting concerns over the lack of treatment effects relative to sham subjects after 12 months.

The road ahead for uniQure: FDA says more data needed for AMT-130 gene therapy – HDBuzz

uniQure's CEO, Matt Kapusta, expressed disappointment over the FDA's decision, emphasizing the need for regulatory flexibility given the severity of Huntington's disease, which currently lacks approved disease-modifying treatments. He stated, “While we respect the agency’s perspective... we believe it’s appropriate to fully and carefully consider how regulatory flexibility is applied in the context of a rare, monogenic, slow-progressive and ultimately fatal neurodegenerative disorder.”

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The FDA's stance has drawn criticism from various stakeholders, including Stephen Majors from the Alliance for Regenerative Medicine, who noted the inconsistency between the FDA's commitment to regulatory flexibility and its recent demands for more rigorous trial designs.

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The FDA's decision has faced backlash from patient advocacy groups and analysts, who argue that the agency's heightened requirements could hinder access to potentially life-saving therapies for rare diseases. A petition on Change.org, initiated by a Huntington's family member, has garnered over 40,000 signatures urging the FDA to approve AMT-130 based on existing data. Critics highlight the ethical implications of requiring invasive procedures for sham surgeries, which could impose significant risks on patients.

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There is a notable discrepancy between uniQure's previous understanding of the FDA's guidance and the current requirements. Initially, the FDA had indicated that data from the Phase 1/2 study could serve as a basis for a biologics license application (BLA). However, the recent communication suggests a reversal, leaving stakeholders uncertain about the regulatory landscape for gene therapies targeting rare diseases.

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uniQure plans to engage further with the FDA, requesting a Type B meeting in the second quarter of 2026 to discuss potential Phase 3 study designs. The company also intends to update its statistical analysis plan to include a four-year analysis to demonstrate AMT-130's treatment durability. Meanwhile, uniQure is exploring regulatory pathways in Europe, where ongoing trials may provide additional data to support its case.

The road ahead for uniQure: FDA says more data needed for AMT-130 gene therapy – HDBuzz

• “The FDA strongly recommended uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study,” — uniQure

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• “While we did not reach alignment on a submission pathway based on the Phase I/II data, we believe the totality and durability of our data warrant continued substantive dialogue regarding how the FDA’s stated commitment to regulatory flexibility may be appropriately applied in this setting.” — Matt Kapusta, CEO of uniQure

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• “ARM implores the FDA to back up its positive rhetoric about cell and gene therapies and rare diseases with concrete, common-sense actions that will quickly restore confidence among patients, companies, and investors.” — Stephen Majors, VP of Global Communications, Alliance for Regenerative Medicine

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The FDA's rejection of uniQure's AMT-130 approval pathway underscores the complexities and challenges faced by companies developing therapies for rare diseases, as regulatory expectations evolve in response to emerging data and ethical considerations.

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