uniQure falls on long-term Huntington's gene therapy data

uniQure's gene therapy for Huntington's continued to slow disease progression over four years of follow-up in a clinical trial, but signs that efficacy may be starting to wane spooked investors.

Shares in Nasdaq-listed uniQure were trading down more than 39% today after the company released the updated results from the phase 1/2 study of ifezuntirgene inilparvovec (AMT-130), despite what the company called a "meaningful slowing of disease progression" in 12 patients followed for 48 months after the one-shot treatment.

The gene therapy is currently under regulatory review by the FDA, which agreed to consider the marketing application in June, after turning it down last year with a request for another clinical trial. After negotiations, the US regulator said it would accept data from the phase 1/2 trial, which compared the gene therapy to an external control, based on three-year follow-up data. uniQure has also submitted it for approval in the UK.

In its update, uniQure said there was a 44% slowing of disease progression in the 12 subjects measured using the cUHDRS scale, and 61% on using the TFC scale, compared to historical controls. The cUHDRS result did not reach statistical significance, while for TFC it just crossed that threshold.

Updated three-year data – in 15 subjects – was more positive, with improvements of 80% and 67%, respectively, on cUHDRS and TFC that were also nominally significant, according to uniQure, which said the figures show a "substantial effect…further reinforcing the data included in our license applications."

The company said the 48-month results were "likely understated by substantial missing data and survivor bias" in an updated external control, but the scale of the sell-off suggests it will have its work cut out convincing investors there is nothing to worry about.

Using the previous external control group, AMT-130 performed somewhat better, with a 54% improvement on cUHDRS and a 68% improvement on TFC that were both statistically significant.

Victor Sung of the University of Alabama at Birmingham (UAB), who is director of UAB's Huntington's disease clinic, pointed out that TFC "tracks things that matter the most to patients and families – ability to work, perform household chores and handle daily self-care activities."

There is intense interest in the progress with AMT-130 as, at the moment, there are no disease-modifying therapies that can slow disease progression approved for Huntington's, with all current drugs tackling symptoms only. It affects an estimated 30,000 to 41,000 people in the US.

"We believe these data are clinically meaningful for Huntington’s disease patients, and we look forward to presenting them at a future scientific meeting," said uniQure chief medical officer Walid Abi-Saab.