- UniQure can begin treating patients with the highest dose of its experimental Huntington's disease gene therapy, announcing Thursday that clinical trial monitors found no safety concerns after reviewing data from the first 10 participants who received lower doses.
- The safety panel's go-ahead clears the way for the Massachusetts-based company to enroll another 16 patients. The trial is primarily assessing the safety of the gene therapy, called AMT-130, but will also measure biomarkers, cognition and motor function.
- Huntington's disease drug development has seen two major setbacks, with Roche halting dosing of partner Ionis Pharmaceutical's drug tominersen and Wave Life Sciences canceling two separate programs. UniQure may have more signs of how well AMT-130 works later this year when brain scans and other biological tests of the first patients treated in the trial will be available.
After Ionis announced, without detailing why, that Roche had stopped dosing in the tominersen trial on the advice of its trial's data monitors, investors have wondered what would happen when AMT-130 went under the same review, wrote Paul Matteis, an analyst at Stifel. That worst-case scenario has not materialized, although AMT-130 has a long way to go to prove it can alter the course of Huntington's disease.
Tominersen and Wave's two candidates, WVE-120101 and WVE-120102, aimed to block portions of patients' genetic code that resulted in a mutant form of the protein huntingtin, which is linked to neurodegenerative decline. All three were delivered by spinal injections.
AMT-130, by comparison, uses adeno-associated viruses to deliver artificial microRNA to silence the gene signaling the production of the mutant protein. Because it is implanted via surgery into brain tissue, treatment could in theory result in greater uptake among diseased cells, Joseph Schwartz, an analyst at SVB Leerink, wrote in a May 27 note to clients.
The announcement Thursday gives no insight into that question, however. The trial's data safety monitoring board gave the go-ahead for the high-dose group, expected to begin receiving AMT-130, after reviewing safety measures from the first 10 patients in the trial, four of whom have received a sham procedure that involves skin incisions only. The longest follow-up is in the first two patients, which received the gene therapy nine months before the safety review.
In the high-dose group, 10 patients will receive AMT-130 and six a sham procedure.
Whether AMT-130 actually helps patients won't be clear for some time. Later this year, UniQure could get some early signs, with magnetic resonance imaging measuring brain and nervous system shrinkage from the first four patients serving as a key indicator that the gene therapy may be slowing disease progression.
While Wave and Ionis have met setbacks, UniQure still has company in developing a gene therapy for Huntington's, including Voyager Therapeutics.
Neurological diseases like Huntington's are of high interest for gene therapy developers. According to a count by Cowen, an investment bank, a third of all disclosed preclinical or clinical gene therapy programs as of January 2021 were in neurology.