FDA Reverses Course on uniQure's Huntington's Gene Therapy
Updated: 1 day ago
On June 17, 2026, uniQure announced that the FDA had agreed its three-year clinical data for AMT-130 could support an application for accelerated approval in Huntington's disease. It was a stunning reversal. In late 2025, FDA officials had questioned whether the same data were strong enough. Investors reacted immediately. uniQure's shares jumped nearly 80% in a day.
The company went on to file its application with the FDA, and with UK regulators, on September 2. If approved, AMT-130 would be the first gene therapy for Huntington's disease.
A disease written in repeats
Huntington's disease is caused by a stretch of repeated DNA letters, CAG, in the HTT gene. Most people have fewer than about 36 repeats. People with Huntington's have more. The expanded gene produces a toxic version of the huntingtin protein that slowly damages neurons, especially in a brain region called the striatum, which helps control movement, mood, and thinking.
Symptoms usually start in mid-adulthood. They include involuntary movements, psychiatric changes, and cognitive decline that progresses over 15 to 20 years. The disease is dominantly inherited, so each child of an affected parent has a 50% chance of carrying it. There are treatments for some symptoms, but nothing that slows the disease itself.
How AMT-130 works: silencing the message
AMT-130 doesn't replace or repair a gene. It lowers the amount of huntingtin protein the brain makes.
It uses an AAV5 vector carrying a gene that encodes a small microRNA. Once inside neurons, that microRNA finds the messenger RNA copies of the huntingtin gene and marks them for destruction. Less mRNA means less protein, including less of the toxic form. If the HTT mRNA is silenced continuously, huntingtin protein levels in treated neurons should stay lower over time.
Delivery is precise and demanding. AMT-130 is infused directly into the striatum during a neurosurgical procedure. It's given once and meant to keep working for years.
What the data showed
The key results come from uniQure's Phase 1/2 trials. Among 12 patients who received the higher dose, disease progression slowed by 75% after three years. That comparison was made against an external control group drawn from Enroll-HD, a large database that tracks how Huntington's naturally progresses in untreated people.
That external control is at the heart of the controversy. Randomized, placebo-controlled trials are the gold standard. In a neurosurgical gene therapy trial, though, a placebo arm would mean sham brain surgery, which raises real ethical and practical problems. The question is whether a well-matched natural-history comparison is reliable enough to count.
Why the FDA changed its mind
In late 2025, FDA leadership signaled doubts about relying on the external control. That left uniQure's path uncertain and suggested the company might need a new, larger trial, adding years.
Then the agency changed. Between April and May 2026, several senior figures departed, including Commissioner Marty Makary and Vinay Prasad, who had overseen the office responsible for vaccines and gene therapies. By June, the FDA confirmed the existing data could support accelerated approval.
Analysts at RBC Capital Markets described the shift as "the pendulum between regulatory leniency vs inflexible scientific rigor" swinging back toward flexibility. uniQure wasn't the only company affected. The same month, Regenxbio said it had aligned with the FDA on a path to resubmit its Hunter syndrome gene therapy without new patients. (That plan later ran into trouble of its own.)
The two sides of the debate
The case for flexibility: Huntington's is relentless and has no disease-modifying treatment. A 75% slowing over three years, if real, would be enormous. Accelerated approval lets patients get access while confirmatory evidence is gathered.
The case for caution: Twelve patients is a small group, and external controls can introduce bias. People who enroll in trials may differ from those in a registry in ways that affect how quickly the disease progresses. If the effect proves smaller than it looks, patients will have undergone brain surgery for an uncertain benefit.
Both points are serious. That's why the confirmatory evidence required after any accelerated approval will matter so much.
What happens next
uniQure filed its application on September 2. If the FDA grants priority review, a decision could come around late April or early May 2027. Analysts at William Blair estimate peak global sales could reach $3.2 billion by 2035, reflecting both the size of the unmet need and AMT-130's potential as a first-in-class treatment.
The bottom line
For families living with Huntington's, June brought news many had stopped hoping for. The science behind AMT-130 hasn't changed. What changed was the FDA's view of how much evidence is enough. Whether that shift is a welcome dose of pragmatism or a risky lowering of the bar is a debate that will follow this therapy all the way to a decision.
Keep exploring with Gene Tech Times
Free guide: subscribe to the Gene Tech Times Briefing on our homepage and get Every FDA-Approved Gene Therapy at a Glance in your inbox.
Watch: 30-second gene therapy Shorts on Gene Tech Times Academy.
Read: The Cheat Codes of Our Genes, real stories of mutations that make some people immune to disease.
New to gene therapy? Start with The Life-Changing Power of Gene Therapy.
— T.N., Gene Tech Times
Comments