UniQure's stock plummets after data drop for Huntington's disease gene therapy

UniQure’s stock has hit a six-year low after interim data for a study evaluating its investigational gene therapy for Huntington’s disease revealed not-so-straightforward results.

The biotech’s stock cratered nearly 40% Wednesday morning to $12 per share, pricing the biotech hasn’t seen since 2017. This is compared to a $19.44 closing price Tuesday night.

The stock plummet is tied to an interim data release for a phase 1/2 clinical trial assessing uniQure's investigational gene therapy for Huntington’s disease, a rare inherited brain disorder that progressively breaks down nerve cells. The therapy, known as AMT-130, was previously scrutinized after safety signals prompted a pause in dosing for two groups in an open-label, European phase 1/2 trial of the drug. The pause, which was recommended by a safety monitoring board after three patients were hospitalized with various symptoms, was lifted in November.

Now, the company has shared fresh data from 26 patients with early-stage Huntington’s in a placebo-blind, multicenter U.S. trial. Six patients received a low-dose treatment while 10 were part of the high-dose cohort; the rest received placebo. The proof-of-concept study consists of a blinded 12-month period followed by unblinded long-term follow-up for treated patients. The newest data were taken two years after the trial launched for the low-dose group and after one year for the high-dose group.

The interim data showed that the therapy was generally well tolerated with a manageable safety profile in both cohorts, according to uniQure.   

The most commonly reported adverse events were related to the therapy’s administration; AMT-130 is surgically delivered directly into the striatum region of the brain.

Two serious adverse events (SAEs) were reported in the low-dose cohort, one in the high-dose arm and one in the control group, all of which were determined to be unrelated to AMT-130. The biotech also reported two suspected unexpected SAEs (severe headache and central nervous system inflammation) in the high-dose cohort, though the company did not specify if the events were related to treatment or not. All SAEs have resolved, according to uniQure.

Patients in both treatment arms showed an increase on the total motor score, a scale developed by the Huntington Study Group to measure clinical symptoms. Patients in the low-dose cohort showed a mean improvement of 1.8 points in total motor score at the two-year mark, while patients in the high-dose group had an average 2.7-point improvement after one year. Patients in the control group had a worsening total motor score after one year, according to uniQure.

The company also documented improvements in both treatment groups for total functional capacity and disease progression.

UniQure also looked at neurofilament light chain levels, a protein that can be used as a biomarker for neurodegenerative diseases. Higher levels of the protein are tied to disease progression. After two years, the low-dose group saw average neurofilament light chain levels drop 12.9% below baseline. However, the high-dose arm experienced a 51.5% jump after one year, though two high-dose patients had levels drop to 27.4% at 18 months, suggesting levels may decline with time.

The company also examined levels of mutant Huntingtin protein, which plays a key role in the disease’s progression. Patients in the low-dose group had an 8.1% decline in protein levels after two years, while the high-dose arm had a 39.7% increase at one year. Those figures compared to a 4.7% rise for the placebo group.   

While stockholders were less than thrilled by the new data, uniQure is encouraged by the results.

“We are very pleased with the data from the interim analysis of our U.S. phase 1/2 clinical trial of AMT-130,” uniQure R&D President Ricardo Dolmetsch, Ph.D., said in a June 21 release.   

Based on the interim analysis, uniQure is planning to discuss further clinical development of AMT-130 with regulators by the first quarter of next year, according to Dolmetsch.

In the meantime, the company plans to wrap up enrollment in the high-dose cohort of the European trial early in the third quarter of 2023.

UniQure is also set to launch a third cohort in the ongoing U.S. trial sometime this year to further assess both doses in combination with surgical immunosuppression.

All this follows the November FDA approval of uniQure’s and CSL Behring’s hemophilia B gene therapy dubbed Hemgenix. The treatment is not only the first gene therapy approved for the rare disorder but also the most expensive drug in the U.S., sporting an eye-popping price tag of $3.5 million per dose.