New FDA knockback hits uniQure and Huntington patients hard

uniQure looks like it may have to run another trial of its Huntington's disease gene therapy AMT-130, as the FDA will not accept a filing based on its current clinical data.

Shares in the Netherlands-headquartered company, already depressed by the FDA's refusal to accept its filing for AMT-130 last November and speculation about the programmes in the last few days after comments from FDA Commissioner Marty Makary in an interview with CNBC, lost around 44% of their value after the company revealed the outcome of a meeting with the US regulator.

uniQure held a Type A meeting with the FDA at the end of January and, in a statement released today, said the agency "cannot agree that data from the Phase I/II studies, compared to an external control, are sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130."

It added that the FDA has "strongly recommended" that it carry out a randomised, double-blind study comparing AMT-130 – which is administered as a single dose via injection directly into the brain during a surgical operation – to a sham surgery procedure.

uniQure's phase 1/2 trial – the protocol for which was agreed with the FDA in 2024 – compared the gene therapy to a natural history external control.

Now, the company says it will seek a follow-up, Type B meeting with the FDA to explore what might be required for a phase 3 trial. It's worth noting that a phase 3 programme will likely result in an extensive delay, and some genetic therapy developers, such as Taysha in 2023, have abandoned projects after being told they have to run additional studies.

Huntington's, which affects an estimated 30,000 to 41,000 people in the US and is classed as a rare disease, causes neurons in the brain to decay over time and leads to physical deterioration as well as cognitive and mental health problems. AMT-130 is designed to switch off a mutation in the huntingtin gene and prevent it from producing a toxic form of the protein that attacks nerve cells.

In uniQure's phase 1/2 trial, the gene therapy was associated with a statistically significant 75% slowing of disease progression three years after the one-shot treatment was administered compared to historical controls.

"While we did not reach alignment on a submission pathway based on the phase I/II data, we believe the totality and durability of our data warrant continued substantive dialogue regarding how the FDA's stated commitment to regulatory flexibility may be appropriately applied in this setting," said Matt Kapusta, the biotech's chief executive.

"We remain committed to engaging with the FDA to determine a clear, scientifically grounded, and efficient path forward for AMT-130," he added.

The latest announcement will doubtless be greeted with consternation by patient groups, as there are no approved therapies that tackle the underlying disease mechanism, and has raised eyebrows considering the FDA's much-trumpeted plans for measures that will speed up access to rare disease therapies.

At a meeting of the US Senate Special Committee on Aging last week, lawmakers and patient advocates said the FDA's handling of therapies for rare diseases has been inconsistent and overly cautious, with questions raised about its stance on Biohaven's troriluzole candidate for spinocerebellar ataxia (SCA).