uniQure poleaxed as FDA blocks Huntington's therapy

Dutch biotech uniQure has lost around half of its value after revealing that the FDA has indicated it is not prepared to review its gene therapy for Huntington's disease, which currently has no recognised treatments.

Shares were down more than 53% to around $31.60, a sharp fall, but still ahead of the value of the stock before it revealed that the AMT-130 gene therapy met its primary efficacy objective in the phase 1/2 trial in September.

AMT-130 is administered as a single dose via injection directly into the brain, in a surgical operation lasting over 12 hours, and consists of an adeno-associated virus (AAV) vector carrying a micro-RNA that is designed to switch off a mutation in the huntingtin gene and prevent it from producing a toxic form of the protein that attacks neurons in the brain.

In the study, the therapy achieved a statistically significant 75% slowing of disease progression three years after the one-shot treatment was administered.

Sadly, after that euphoric announcement, which was also celebrated by patient organisations like the Huntington's Disease Association (HDA) in the UK, uniQure has now been brought back to earth with a bang.

The company said it has just completed a pre-Biologics License Application (BLA) meeting with the FDA to gauge whether its data is strong enough to support a filing. Unfortunately, it now seems that the US regulator no longer believes that the protocol used in the trial is adequate to support a review.

Specifically, it seems to have lost confidence in comparing AMT-130 to an external control, according to uniQure's statement. If it now seeks a placebo-controlled assessment of AMT-130, the programme could be in for a lengthy delay.

"We are surprised by the FDA's feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing phase 1/2 studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the accelerated approval pathway," said uniQure's chief executive, Matt Kapusta.

"This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease."

The news has raised further questions about the direction of US regulation of cutting-edge therapies, given the rejections earlier this year of Replimmune's oncolytic virus RP1 for melanoma and Capricor Therapeutics' cell therapy deramiocel for Duchenne muscular dystrophy, even as it tries to lower hurdles for generics and biosimilars.

While the path to US approval now seems uncertain – uniQure will need to wait for the final minutes from the FDA meeting to gauge the impact – the company said it intends to press on with discussions with regulators in Europe, including the UK's MHRA.

There was more encouraging news for uniQure from the UK regulator, which said today that it intends to "overhaul the rulebook" for rare disease therapies to make it quicker and easier to get them "tested, manufactured, and approved" in the UK.

"The successful results of the AMT 130 trial have not changed," commented Cath Stanley, HDA chief executive.

"It seems the USA will not be fast-tracking the drug as previously agreed, so the timeline previously shared about where and when the drug will be available in the US has now changed," she added. "However, the UK regulatory body is independent of others; this decision today will not influence what happens here, and today's news from MHRA may have the potential to accelerate the decisions of MHRA for treatments like this."