The trial involved enrolling 46 patients with early Huntington’s disease at 9 study centres in the UK, Germany and Canada. Each patient received four doses of either IONIS-HTTRx or placebo, given by injection into the spinal fluid to enable it to reach the brain.
As the phase 1/2a trial progressed, the dose of IONIS-HTTRx was increased several times according to the ascending-dose trial design. Patient safety was monitored throughout the study by an independent safety committee.
The announcement at completion of the trial confirms that IONIS-HTTRx was well-tolerated by the trial participants and its safety profile supports further testing in patients. Professor Tabrizi, Director of the UCL Huntington’s Disease Centre and IONIS-HTTRx Global Chief Investigator, said:
“The results of this trial are of ground-breaking importance for Huntington’s disease patients and families. For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”
A major unknown was whether the trial would show that IONIS-HTTRx could lower the level of mutant huntingtin protein in the nervous system. Using an ultra-sensitive assay, concentrations of the protein were measured in each patient’s spinal fluid before and after treatment.
As hoped, IONIS-HTTRx produced significant, dose-dependent lowering of the level of mutant huntingtin – the first time the protein known to cause Huntington’s has been lowered in the nervous system of patients.
As a result of these successful outcomes, Ionis’ partner, Roche, has exercised its option to license IONIS-HTTRx and assumes responsibility for further development, regulatory activities and commercialisation activities. Meanwhile, Ionis announced in June that all patients in the completed trial would be offered a place in an open-label extension to receive IONIS-HTTRx.
The results of the trial and plans for the ongoing IONIS-HTTRx programme will be presented in detail at forthcoming scientific meetings and prepared for peer-reviewed publication.
The research is supported by The National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. The centre is a partnership between UCL and University College London Hospitals NHS Foundation Trust funded by the NIHR to translate scientific breakthroughs into better patient treatments.
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