Ionis Announces Positive Top-Line Data

Ionis Pharmaceuticals has presented positive top-line data from a completed Phase 1/2 study of IONIS-HTTRx (RG6042) in people with early stage Huntington’s disease. The data demonstrates that IONIS-HTTRx (RG6042) is the first drug in development to lower the disease-causing protein in people with HD. 

HD is a rare, progressive, neurodegenerative disease caused by genetic mutation in the huntingtin gene, which results in the production of a toxic protein, the mutant huntingtin (mHTT) protein, which gradually destroys neurons in the brain resulting in deterioration in mental abilities and physical control. Ionis designed IONIS-HTTRx (RG6042), a Generation 2+ antisense drug, to specifically reduce the production of all forms of the huntingtin protein, including mHTT.  

“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. 

In the study, 46 people with early stage Huntington’s disease were treated for 13 weeks with four intrathecal injections of 10 mg, 30 mg, 60 mg, 90 mg or 120 mg of IONIS-HTTRx (RG6042) or placebo, administered monthly. Significant, dose-dependent reductions in mHTT were observed in CSF of treated participants with mHTT reductions of up to approximately 60% and mean reductions of approximately 40% in CSF observed at the two highest doses. 

Roche has been working closely with Ionis on this program since 2013 and is now leading the development of IONIS-HTTRx (RG6042) and collaborating with the HD community. Roche is currently planning a pivotal trial to determine the clinical efficacy and safety of IONIS-HTTRx (RG6042).

“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.”