FDA Reverses Course on uniQure Huntington's Gene Therapy, Clearing Path to Q3 Filing

What Changed

As of Wednesday, June 17, 2026, uniQure has a green light from the FDA to file a biologics license application for AMT-130, its Huntington's disease gene therapy, based on three-year data from a Phase 1/2 study. The FDA had rejected that same data as insufficient as recently as March 2026, according to pharmaphorum.

The about-face came after uniQure arranged a follow-up Type B meeting with the agency. Out of that meeting, the FDA communicated that three-year Phase 1/2 trial results would serve as "the primary basis" for an accelerated approval BLA, uniQure stated in its June 17 press release. The company plans to submit in the third quarter of 2026.

The Data Behind the Filing

In uniQure's Phase 1/2 trial, AMT-130 was associated with a statistically significant 75% slowing of disease progression three years after a single-dose treatment, measured against historical control data, according to pharmaphorum. That comparison to historical controls, rather than a concurrent control group, had been the FDA's original sticking point.

Huntington's disease affects an estimated 30,000 to 41,000 people in the U.S. It causes progressive neuronal decay, leading to physical deterioration and cognitive decline. Zero disease-modifying therapies are currently approved. Every drug on the market only addresses symptoms like involuntary movement. AMT-130 targets the HTT gene mutation using RNA interference, blocking production of the toxic huntingtin protein.

The Stock Reaction

Shares of uniQure opened Wednesday up roughly 62% to $44, according to BioSpace. Premarket, Fierce Biotech reported shares as high as $48.51, a gain of approximately 80%. For context, pharmaphorum noted the stock had been trading above $70 before the FDA's original refusal-to-file decision and had closed at $26.99 on Tuesday.

Small share-price upticks were also seen in Rezolute and Regenxbio, per Fierce Biotech, which noted investors may be reading the FDA's flexibility as a broader signal on rare disease evidence standards.

Stifel's reaction was blunt. The firm's Wednesday morning note to investors, cited by BioSpace, opened with "WOW" and described the development as "a ~180 from FDA."

What's Driving the Regulatory Shift

Guggenheim Securities analysts pointed to a structural explanation: the FDA's "appreciation of the challenges in rare disease following the overhaul of its leadership," according to Fierce Biotech. Former FDA Commissioner Marty Makary and former FDA official Vinay Prasad had both been in place when uniQure first pressed for accelerated approval. Both have since left the agency. BioSpace noted uniQure's stock had already begun climbing in May on rumors of Makary's impending departure, citing investor sentiment that his exit could ease the regulatory posture.

Leadership change does not automatically mean standards got looser. It may mean the agency reassessed a genuinely difficult evidentiary question in rare disease, where randomized controlled trials face real ethical and logistical constraints. Attributing the reversal purely to political personnel shifts is a partial read.

The Sham Surgery Question

One concrete piece of the regulatory picture also shifted. The FDA had previously insisted on a sham surgery-controlled Phase 3 confirmatory trial before it would consider full approval. Sham procedures, in which patients undergo the same surgical process as treated patients but receive no actual therapy, are considered by many researchers and patient advocacy groups to be ethically unacceptable for a fatal, progressive disease with no alternatives, according to BioSpace.

The FDA has now signaled it may accept a standard-of-care control design instead, which would mean comparing AMT-130 patients to patients receiving existing symptom-management drugs rather than a placebo surgery. That is not a final agreement. UniQure and the FDA still need to align on the confirmatory study design before the BLA submission, and uniQure noted the agency "seeks to align on the confirmatory study design prior to the BLA submission."

Strongest Counterpoint

Critics of accelerated approval pathways have a legitimate concern: the program has a track record of approvals that later failed in confirmatory trials, sometimes leaving patients exposed to drugs with uncertain benefit. Phase 1/2 data against historical controls, rather than a randomized concurrent comparator, carries real uncertainty. The 75% slowing figure is striking, but it comes from a small early-phase study and is compared to external historical data, not a blinded control group. Those asking the FDA to hold the line on more rigorous evidence before granting marketing approval have a reasonable point. The question is whether that standard is achievable, or whether it imposes a barrier that, in practice, means no treatment ever reaches Huntington's patients.

What Comes Next

UniQure CEO Matt Kapusta said in the company's press release, quoted by pharmaphorum: "The consistency and strength of the clinical data generated to date give us great confidence in the product's potential to make a meaningful difference for patients."

The company still needs to receive formal written minutes from its FDA meeting before it can proceed with filing. Pharmaphorum flagged that procedural step explicitly. Confirmatory trials under accelerated approval typically need to be underway at the time of FDA action, and in some cases the agency requires full enrollment before granting approval, per Fierce Biotech. How the FDA structures that requirement for AMT-130, given the ongoing debate over trial design, is the central unresolved question between here and any potential approval, which pharmaphorum projected could come as early as 2027.