Roche & Ionis Huntington’s Drug Shows Huge Capabilities in Early Trial
Three months after Pharma gaint Roche forked over a payment of $45 million for rights to Ionis Pharmaceuticals, the latter’s “breakthrough” drug IONIS-HTTRx for the treatment of Huntington’s disease has showcased that the treatment is effective in lowering the mutant huntingtin (mHTT) protein, which destroys neurons in the brain and results in a decline in mental abilities and physical control.
Huntington’s is a progressive neurodegenerative disease affecting mental abilities and physical control that normally hits sufferers between the ages of 30 and 50 years before continually worsening over a 10- to 25-year period. There is currently no effective disease-modifying treatment for the condition, with existing medicines focused only on managing disease symptoms.
The researchers involved with the study said they tracked a mean reduction of 40% in mutant huntingtin protein at the two highest doses of the therapy. Some patients saw up to 60% reductions. And that, they add, is a first for any Huntington’s drug. If they’re right, the developers are on track to the first potential drug that could change the course of
the disease, though some steep hurdles on safety and efficacy remain to be cleared.The number of people who received the two highest doses is small. Investigators enrolled 46 people in the trial and randomized them to receive one of five doses of RG6042 or placebo. Roche needs to treat more people with the highest doses before reaching concrete conclusions about the effect of the drug.
Roche has been working with Ionis on this program since 2013 and is now leading the development of IONIS-HTTRx (RG6042) after acquiring the rights last year. The Swiss-based pharma giant is planning a pivotal trial to determine the clinical efficacy and safety of IONIS-HTTRx (RG6042). An open-label extension study for patients who participated in the Phase I/II study is ongoing.
“For nearly twenty years, I have seen many families devastated from losses to this progressive neurodegenerative disease. With IONIS-HTTRx (RG6042), the HD community has new hope for a therapy that can reduce the cause of HD, and therefore, may slow the progression and potentially prevent the disease in future generations, which is truly groundbreaking,” said Dr. Sarah Tabrizi, professor of clinical neurology, director of the University College London’s Huntington’s Disease Centre and the global lead investigator on the study. “I look forward to a longer-term, larger study that can establish the benefit of reducing the toxic mutant huntingtin protein in people with HD.”
“We designed IONIS-HTTRx to treat all patients with HD. These important clinical results demonstrate that our approach of targeting the toxic mutant huntingtin protein can significantly reduce the underlying cause of this terrible disease. In this study, we were able to achieve mutant huntingtin protein reductions in study participants that were higher than those that produced disease benefit in preclinical models of HD,” added Dr. C. Frank Bennett, senior vice president of research and franchise leader for the neurological programs at Ionis Pharmaceuticals. “We were pleased that this antisense approach, which targets all forms of the huntingtin protein, proved to be safe and well tolerated in this study. We look forward to working with Roche to quickly advance IONIS-HTTRx (RG6042) into a pivotal study, which we hope will lead to marketing approval for this new drug for people with HD.“
