Exciting news for the rare disease community: For the first time a therapy has been shown to slow the progression of Huntington’s disease, giving hopes to patients suffering from the terrible, incurable disorder. In what the Huntington’s Disease Society of America has hailed as “a historic moment in the fight against” the disease, an experimental drug has reduced levels of the toxic protein that causes Huntington’s disease in humans.
Huntington’s disease is an inherited disorder in which mutant forms of the huntingtin protein damage nerve cells in the brain. The new drug, Ionis-HTTRx, was shown to be safe in humans and lowered levels of a toxic protein that causes the devastating genetic disease.
Scientists at UK’s University College of London enrolled 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.
The trial investigators confirmed that IONIS-HTTRx was well-tolerated and its safety profile supports further testing in patients.“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.” Professor Tabrizi, Director of the UCL Huntington’s Disease Centre and IONIS-HTTRx Global Chief Investigator.
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 commercialization 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.