UniQure unveils mixed Huntington’s gene therapy data, shares tank

UniQure shared updated data from a Phase I/II study that showed a clinical benefit in a small group of patients with Huntington’s disease who received its gene therapy, but conflicting data about the mutant Huntingtin protein sent shares $QURE down by about 40% on Wednesday morning.

The Dutch biotech on Wednesday revealed new data from the placebo-controlled Phase I/II study with 26 patients. Sixteen patients were given a low or high dose of AMT-130, with 10 patients in the control group.

The patients in the low dose group showed an average 1.8 point increase in total motor score, a measure of motor symptoms, at two years, while the high dose group demonstrated a 2.7 point increase at one year. UniQure did not share data for the low dose group at the 12-month mark.

The company also reported improvements in two other endpoints: total functional capacity, a measure of daily life activities, and the composite Unified Huntington’s Disease Rating Scale, which tracks progression of the disease.

UniQure noted four serious adverse events that it said were unrelated to the one-time gene therapy.

“At face, we’re positively surprised that multiple clinical measures look favorable for AMT-130,” Stifel analyst Paul Matteis told investors. “Moreover, at two years, neurofilament is below baseline, encouraging considering the historical tominersen overhang. The one caveat to the above: the mHTT data are very confusing and are discordant with the prior one-year data.”

A year ago, uniQure reported a 53.8% mean decrease in mutant Huntingtin protein, or mHTT, in cerebrospinal fluid (CSF) in four patients in the low dose group after one year. But the updated data showed a mean decrease of 8% in the low dose group over two years and a 40% increase in mHTT in the high dose group at one year, compared to a 4.7% increase in the control group at one year.

Ricardo Dolmetsch

“There is a lot of variability in mutant Huntingtin in CSF that we don’t understand,” Ricardo Dolmetsch, uniQure’s president of R&D, told Endpoints News.

The biotech plans to start a third cohort in the US trial looking at different immunosuppression regimens to prevent serious adverse events, which resulted in several patients being hospitalized last year. Dolmetsch said uniQure believes those events likely stem from a reaction to infusions.

“We are cautiously optimistic that we can manage that side effect,” Dolmetsch said, adding that all patients are now being dosed with perioperative steroids.

The company expects to finish enrolling an open-label Phase I/II study in Europe in the third quarter, with plans to reveal more data this year, including longer follow-up data for US patients and the first data for patients in Europe. The difference between the US and the European trials is that the US trial is placebo-controlled.

Meanwhile, PTC Therapeutics revealed data for its Huntington’s therapy on Wednesday. The biotech said PTC518, its oral candidate, showed an average reduction of 30% in mHTT in a Phase II trial after 12 weeks.

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