IONIS-HTT Rx (RG6042) top-line data demonstrate significant reductions of disease-causing mutant huntingtin protein in people with Huntington’s disease.
Ionis Pharmaceuticals, Inc. announced the presentation of positive top-line data from a completed Phase 1/2 study of IONIS-HTTRx (RG6042) in people with early stage Huntington’s disease (HD) at the 13th Annual CHDI HD conference. The data demonstrate 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.
Phase 1/2 Study Results:
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, 90 mg (p<0.01) and 120 mg (p<0.01).
Based on a predictive model developed from data collected in rodents and non-human primates, a 40% to 60% reduction in CSF corresponds to an estimated 55% to 85% reduction in mHTT in the cortex and 20% to 50% in the caudate regions of the brain in humans.
mHTT levels were continuing to decline at the last measurement with further decreases in mHTT anticipated; maximum reduction expected by approximately six months after first dose.
No serious adverse events were reported in treated participants and most adverse events (AEs) were mild and considered to be unrelated to study drug. No participants discontinued from the study.
An open-label extension (OLE) study for patients who participated in the Phase 1/2 study is ongoing.
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).
(Source: Ionis Pharmaceuticals, Inc.)