Roche, Ionis hail Huntington's success, plan pivotal trial

The Roche Tower
The Roche Tower. (Image: Taxiarchos228)

Ionis Pharmaceuticals has shared data from a phase 1/2 trial of its Roche-partnered treatment for Huntington’s disease. The small trial linked the two highest doses of antisense drug RG6042 to a 40% drop in levels of the mutant protein that drives the neurodegenerative disease.

Carlsbad, California-based Ionis indicated it had solid data late last year when it revealed Roche had paid $45 million to license the drug after seeing dose-dependent reductions in mutant huntingtin protein. Now, Ionis has shared a glimpse at the size of the decline in protein levels.

Assay tests linked the two highest doses of RG6042 to a 40% mean reduction in mutant protein and a peak drop of 60%. Those drops were achieved following four intrathecal injections over 13 weeks. With protein levels still declining at the end of the study, Ionis expects to see further reductions over the next 13 weeks.


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Showing RG6042, also known as IONIS-HTTRx, lowers levels of the mutant protein by targeting the messenger molecule responsible for its production is a landmark moment for attempts to treat the disease. But further work is needed to show the effect is real and clinically meaningful.

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.

Further work is needed to show what a 40% decline in mutant huntingtin protein means for patients, too. Preclinical work suggests the 40% to 60% drop seen in the cerebral spinal fluid will translate into a 55% to 85% decline in the cortex and 20% to 50% fall in the caudate regions of the brain. More importantly, the preclinical work suggests those reductions are big enough to yield clinical benefits.

Patients enrolled in the phase 1/2 have moved into an open-label extension that will gather data on the longer-term effects of the drug, which came through the initial study without causing any serious adverse events. In parallel, Roche, which is now in the driving seat, will gear up to run a pivotal trial of the candidate.

Shares in Ionis ticked upward in after-hours trading.

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