FDA Gives uniQure Accelerated Approval Green Light for Huntington's Gene Therapy, Reversing Its Own Position a Second Time

Since our June 17 coverage of the FDA's reversal on accelerated approval, the full picture of how dramatically the agency's position shifted has come into sharper focus, with uniQure's shares surging more than 70% in premarket trading on the news, according to Reuters.

What the FDA Actually Said, and When

The timeline matters here. Under Makary and Prasad, the FDA in November 2025 told uniQure the three-year Phase 1/2 analysis of AMT-130 was insufficient for a regulatory filing. In March 2026, the agency reiterated that position and "strongly recommended" uniQure run a full double-blind study, according to MedCity News. That recommendation struck many rare-disease researchers as impractical — and given that it would mean giving some patients no treatment for a fatal disease, potentially unethical.

Now, following a formal meeting with the reconstituted FDA leadership, the agency has reversed course entirely. The three-year data will serve as the primary basis for a biologics license application. The FDA has also agreed to use patients on standard-of-care treatment as a comparator for the required confirmatory study, rather than a sham procedure. uniQure expects to file in Q3 2026.

The Data Behind AMT-130

AMT-130 is not a pill. It uses an engineered virus to deliver micro-RNA directly into brain cells, silencing the gene responsible for producing the toxic protein fragment that drives Huntington's disease. Administration requires drilling holes in the skull and threading a microcatheter deep into the brain, a one-time surgical procedure, according to MedCity News.

The Phase 1/2 trial was open-label, meaning neither patients nor researchers were blinded to who received treatment. Patients were compared against an external control: a natural history dataset tracking untreated Huntington's progression. That design, according to MedCity News, was previously accepted by FDA leadership before Makary and Prasad took over, then rejected under them, and is now accepted again.

The high-dose group showed a 75% reduction in disease progression over three years on a widely used clinical scale, according to Reuters. September 2025 results also showed statistically significant slowing of progression and reduced blood levels of a protein associated with neurodegeneration.

What Changed at the FDA

Both Makary and Prasad have left the agency. Acting Commissioner Kyle Diamantas met with rare-disease advocacy groups earlier this month, with one attendee describing the meeting as a "breath of fresh air," according to Reuters.

RBC Capital Markets analysts put it plainly in a note cited by Reuters: "We think this is great news for QURE and may suggest that the pendulum between regulatory leniency versus inflexible scientific rigor is swinging back to the former, now that Vinay Prasad and Marty Makary have left the FDA."

Endpoints News, reporting on the same reversal Wednesday, noted that "regulatory flexibility appears to be back on the FDA's menu" and linked the shift directly to the leadership departures.

The Case for the Prior FDA Position

Open-label trials with external controls are inherently less rigorous than randomized controlled trials. The external control, a natural history dataset, is not a matched group of patients randomized at the same time under the same conditions. Prasad, a well-published oncologist and biostatistician, built his career on exactly this critique: that surrogate endpoints and uncontrolled comparisons can mislead regulators and ultimately harm patients if a drug that looks effective in an early trial turns out not to be.

The counterargument, which now appears to have won at FDA, is that Huntington's disease has no approved disease-modifying treatment, the condition is uniformly fatal, and demanding a sham-surgery placebo arm as the standard of comparison is an ethical barrier that would delay or kill development of any surgical intervention for this disease. Prior FDA leadership had accepted that logic. The current leadership has returned to it.

No Charges, No Investigation

No regulatory or legal action has been filed against uniQure or against former FDA officials related to these decisions. The reversal is a policy and scientific judgment call, not a legal or enforcement matter.

What Comes Next

The concrete unresolved question is whether the accelerated approval pathway will hold up after filing. Accelerated approval is granted on the basis of a surrogate or intermediate endpoint — in this case, the clinical progression scale — with a confirmatory trial required afterward. If that confirmatory trial, whose design is still being finalized with the FDA, fails to show benefit, the agency can withdraw approval. The design of that study, specifically whether a standard-of-care comparator is scientifically adequate to establish efficacy or whether critics will argue it sets too low a bar, is the dispute that will define AMT-130's regulatory future beyond the Q3 2026 filing.