Joy as uniQure Huntington's therapy clears pivotal trial

uniQure's gene therapy for Huntington's has hit the mark in a clinical trial, raising hopes of the first treatment for the devastating neurodegenerative disease.

Shares in the biotech rose sharply this morning after it announced the AMT-130 gene therapy met its main objective in the phase 1/2 trial with a statistically significant 75% slowing of disease progression three years after the one-shot treatment was administered.

The landmark result has delighted patient organisations, including the Huntington's Disease Association in the UK. Chief executive Cath Stanley said it is a "significant breakthrough" that will "bring much-needed optimism to the Huntington's disease community."

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.

The three-year data marks the end of the trial's main follow-up period, and backs up two-year data reported last year that showed similar effects on disease progression measured using the Unified Huntington's Disease Rating Scale (cUHDRS).

In the new data drop, AMT-130 also met a key secondary endpoint by achieving statistically significant slowing of disease progression measured by total functional capacity (TFC) at 36 months, which was accompanied by significant reductions in the neurofilament light protein (NfL) in cerebrospinal fluid (CSF), a biomarker for nerve degeneration in Huntington's.

Now, with the trial completed, uniQure is preparing to file AMT-130 for approval in the US next year, followed by additional submissions in the EU and UK. The gene therapy already has breakthrough and regenerative medicine advance therapy designations in the US, so it could have a swift passage through the regulatory process.

Prof Sarah Tabrizi of UCL's Huntington's Disease Centre said the data "are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington's disease, where an urgent need persists."

Shares in uniQure rocketed 75% when the two-year data was released, and doubled down on that today with the stock leaping almost 160% at the time of writing.

"This result is the good news we've been working and waiting for, not just a treatment that slows progression of this terrible disease, but one that does so with truly stunning effectiveness," commented Prof Ed Wild, consultant neurologist at the National Hospital for Neurology and Neurosurgery at UCL Hospitals NHS Trust.

"It is nothing less than the dawn of a new age for families impacted by Huntington's disease," he added. "We must now work diligently to turn this breakthrough into something that benefits everyone who needs it."

Earlier this year, PTC Therapeutics and Novartis' experimental therapy for Huntington's, mRNA splicing modifier PTC518 (votoplam), also hit its objective in a potentially pivotal trial, putting another potential treatment on the horizon. The orally-active drug, dosed daily, is also designed to reduce levels of mutant huntingtin.

Photo by Quan Nguyen on Unsplash