- Four patients treated with an experimental gene therapy for the neurodegenerative disorder Huntington’s disease experienced reduced levels of a mutated protein associated with the condition, Dutch biotech UniQure said Thursday, a hopeful sign the experimental drug is working biologically.
- The data were from patients given a low dose of the gene therapy in a Phase 1/2 trial, which is primarily meant to assess safety. UniQure has enrolled a second group who will receive 10 times the dose as the first group, as well as measuring biological markers and disease progression over a total of five years.
- No disease-modifying treatments for Huntington’s disease exist, and experimental genetic treatments developed by Roche and partner Ionis Pharmaceuticals and Wave Life Sciences have had setbacks in the past two years. UniQure’s gene therapy is still likely several years away from reaching regulators, although the company expects to have key data on its effect on patient function next year.
It could be a year before UniQure has clear evidence of whether its gene therapy can alter the course of Huntington’s, which typically results in death 10 to 30 years after first diagnosis. Still, the data released Thursday suggest the drug is at least reaching its intended target.
Code-named AMT-130, the drug delivers a type of RNA that regulates gene expression and is specifically tailored to silence a gene called huntingtin. In patients with Huntington’s disease, that gene produces a mutated form of the huntingtin protein, which is associated with the disease. The therapy is infused into the brain through a surgical procedure.
The data released Thursday came from an evaluation of 10 patients with early disease, six of whom received the treatment and four who underwent a sham procedure. The main goal was to evaluate safety. No drug-related reactions or unexpected adverse events were reported. One patient had a blood clot that resolved with blood thinners after the procedure, while another had post-operative delirium that went away.
Of the patients who received the gene therapy, four had levels of mutant huntingtin protein that could be evaluated in their cerebrospinal fluid. After 12 months, the average reduction in those patients was 54% over the pre-treatment baseline, UniQure said. Mutant protein levels in the patients who didn’t receive the gene therapy declined by an average of 17%, the company said.
The data suggest the trial is “the right experiment, which is to say that we can reduce the amount of the mutant protein in [cerebrospinal fluid],” said Ricardo Dolmetsch, UniQure’s president of research and development. Dolmetsch added that doing so is a “prerequisite” of testing whether lowering mutant huntingtin levels will slow disease progression.
The study also evaluated a second protein biomarker that measures nerve damage. As expected, there was a rise following in patients who received gene therapy, but at 12 months it had declined to 8% above the pre-treatment baseline, UniQure said. Increased levels of that protein were a safety concern in the trial of Roche and Ionis’ drug tominersen.
Paul Matteis, an analyst at Stifel, said in a note to clients that UniQure’s data are a sign the drug is working as intended. “We continue to view the efficacy update including the higher dose cohort next year as the bigger/more definitive catalyst for the program,” he wrote.
UniQure shares rose by more than 20% in morning trading Thursday.