UniQure announced on Monday that it will likely need to conduct a Phase 3 clinical trial for its investigational gene therapy, AMT-130, targeting Huntington’s disease. This comes after the FDA informed the company that data from uniQure’s Phase I/II studies, which used an external control group, are not sufficient to support a marketing application.
According to minutes from a Type A meeting with the FDA, the agency stated: “it cannot agree that data from [uniQure’s] Phase I/II studies, compared to an external control, are sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130.” UniQure had previously aligned with the FDA on protocols and statistical analyses and had anticipated filing for approval following positive three-year results from its pivotal study. However, the agency now maintains that more robust evidence is necessary.
Analysts have raised concerns about this shift. Truist analysts wrote: “FDA’s comments are inconsistent with regulatory flexibility the FDA professes it will exercise in reviewing rare disease drugs for high unmet diseases.”
In recent months, several biotechnology companies have faced similar reversals by the FDA regarding what constitutes acceptable evidence for drug approval. This trend has led some experts to suggest that the regulator may be taking a more restrictive approach.
The FDA has recommended that uniQure undertake a prospective, randomized, double-blind study using sham surgery as a control. The company indicated it would follow this guidance but left open the possibility of further discussion with regulators. UniQure CEO Matt Kapusta said: “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.”
Other analysts also weighed in on these developments. Stifel analysts noted disappointment over the requirement for sham-controlled studies but were not surprised given recent statements by Commissioner Marty Makary and other negative decisions in rare disease drug reviews. They wrote: “We had been hopeful that QURE would be able to reverse the agency’s stance given the unmet need in this fatal neurodegenerative disease and the support from HD advocacy groups.” Truist added: “[I]n the setting of this devastating disease, we think the risk/benefit is skewed in favor of AMT-130.”
Commissioner Makary commented during an interview last week without naming specific products: “There was a product where researchers drilled a burr hole… into people’s skulls… At the end of randomization period it was found no benefit, and yet this is one of drugs we were pressured to approve.”
AMT-130 is administered via intracranial surgery involving drilling holes into patients’ skulls to inject gene therapy directly into brain tissue.
Recent actions by regulators have affected other companies as well. Disc Medicine received a complete response letter last month for bitopertin—intended for treating painful sunlight sensitivity—and REGENXBIO saw its Hunter syndrome gene therapy rejected earlier this year.
UniQure said it plans ongoing engagement with regulators regarding potential designs for future trials and intends to request another meeting with the FDA later this year.
