At 12 months, AMT-130 showed no measurable treatment effect compared to sham subjects. That number matters more than the 75% slowdown reported at 3 years, because the 3-year comparison was not made against a concurrent sham arm. It was made against an external database. The FDA is right to require a prospective, sham-controlled Phase 3 trial before approving this therapy, and the ethical arguments against that requirement, while real, do not override the scientific ones.
What 12 Months of Silence Should Tell Us
I spend most of my time evaluating energy technologies where the pattern is identical: a startup reports dazzling results, but the measurement window and the control group do not survive scrutiny. Press releases do not reduce emissions, and press releases do not slow Huntington's disease.
UniQure's own chief medical officer, Walid Abi-Saab, acknowledged that 1 year is generally insufficient to detect meaningful progression in early Huntington's patients. That is a reasonable explanation for why the 12-month sham comparison showed nothing. It is also a reasonable explanation for why the therapy itself might not work. Both hypotheses fit the data equally well. That ambiguity is exactly what a controlled trial resolves.
The 3-year data compared 12 treated patients to trajectories from the Enroll-HD observational database, which tracks over 20,000 patients. Observational databases are valuable. They are not randomized. They cannot control for the placebo effect of brain surgery, which is documented and substantial in the neurosurgical literature. Nor can they control for selection bias in who enrolls in a gene therapy trial versus who appears in a registry.
Twelve treated patients. No concurrent control arm at the timepoint where the effect appears. This is not a rigorous basis for approving a one-time, irreversible intervention delivered directly into the brain.
The Ethics Cut Both Ways
Edward Wild's point about sham-arm patients losing 3 to 5 years of function is the strongest argument against this trial design. Some patients will progress beyond eligibility. That cost is concrete and painful.
But consider the alternative cost. The FDA approves AMT-130 based on 12 treated patients and an external comparison. Thousands of Huntington's patients undergo brain surgery. The therapy turns out to deliver less benefit than the uncontrolled data suggested, or the benefit fades after 5 years in ways the short follow-up could not detect. Those patients cannot undo the procedure. They made an irreversible choice based on insufficient evidence, and the regulatory system that was supposed to protect them waved it through.
This is a one-size-fits-all gene therapy, as FDA Director Vinay Prasad noted, not a personalized treatment. It is designed for broad deployment across the full Huntington's population. The standard of evidence should match the scale of deployment.
I will grant this: the FDA's reversal was handled badly. Granting Breakthrough Therapy and RMAT designations in June 2025, signaling acceptance of external controls, and then reversing in November introduces exactly the kind of regulatory unpredictability that chills investment in gene therapy development. The process failure is real. The scientific conclusion the agency landed on is still correct.
The EMA's decision to reject sham surgery as unethical and accept natural history controls will provide its own data. If European patients treated under that approval show durable, unambiguous benefit over the next several years, the FDA will have a much stronger evidence base to act on. That is not a reason to delay. It is a reason the global regulatory divergence might actually serve patients well, by generating 2 independent data streams from different trial designs.
Roughly 1,000 Americans die from Huntington's disease each year. Every one of those deaths is an argument for speed. But speed without rigor is how you get approved therapies that do not work, and the history of medicine is full of them. The 48,000 petition signatures represent real desperation from a community with no approved disease-modifying treatment. That desperation deserves a therapy whose benefit has been proven under conditions that leave no room for doubt.
AMT-130 may well be that therapy. Prove it.
