Ingrezza treatment eases chorea across body regions: Trial data
KINECT-HD data show greatest benefits in arms, legs, Neurocrine says
Daily treatment with Ingrezza (valbenazine) eases the jerky, involuntary movements known as chorea across different body regions in people with Huntington’s disease, according to new data analyses from the KINECT-HD trial.
The primary analyses from the Phase 3 KINECT-HD study (NCT04102579) showed that the oral therapy overall reduced chorea severity. The new analyses show that the benefits could be seen across individual body regions, with the most pronounced improvements in the arms and legs.
Developer Neurocrine Biosciences presented the new analyses at the Neuro-Advanced Practice Provider Symposium, held March 16 in New Orleans and hosted by the American Association of Neuroscience Nurses.
“This analysis reinforces the primary study findings, showing the consistent benefit of Ingrezza in reducing the involuntary movements of chorea that can affect any part of the body,” Eiry W. Roberts, MD, chief medical officer at Neurocrine, said in a company press release. The results “are meaningful because they show how Ingrezza alleviates chorea symptoms and therefore helps people with Huntington’s disease in their everyday lives,” Roberts said.
Chorea, which can occur anywhere in the body, is among the most common Huntington’s symptoms. It can hamper patients’ functional independence and life quality.
Evaluating changes in severity
Ingrezza, taken as a once-daily capsule that’s swallowed whole, is approved in the U.S. to treat adults with Huntington’s-associated chorea. It’s thought to work by reducing nerve cells’ release of dopamine, a brain-signaling chemical whose elevated levels have been associated with chorea, through the blockage of a protein called VMAT2. Ingrezza Sprinkle, a capsule formulation that can be opened and sprinkled on food for people with swallowing difficulties, is also available.
KINECT-HD enrolled 128 adults, ages 18-75, with Huntington’s-related chorea. Participants were randomly assigned to receive daily capsules of either Ingrezza or a placebo for 12 weeks, or about three months. The daily dose of Ingrezza was started at 40 mg and could be titrated up to a maintenance dose of 80 mg, as tolerated.
The trial’s main goal was to evaluate changes in chorea severity, as assessed by the Total Maximal Chorea (TMC) score of the Unified Huntington’s Disease Rating Scale.
TMC evaluates chorea across seven distinct body regions: the face, mouth/jaw, trunk, the left and right upper extremities (arms and hands), and the left and right lower extremities (legs and feet). Each item is scored from 0-4, with higher scores reflecting more severe chorea. These individual scores are added for an overall chorea severity score.
Results from KINECT-HD showed that Ingrezza treatment was associated with significant reductions in overall chorea scores relative to the placebo, meeting the study’s main goal. Specifically, TMC total scores dropped by 4.6 points on average after three months on Ingrezza, compared with a 1.4-point decline in the placebo group.
Subsequent data analyses showed that the therapy eased chorea regardless of factors such as sex, age, or disease severity.
The researchers conducted new analyses to look at chorea severity changes in the individual body regions assessed with TMC. A potentially meaningful reduction was defined as a TMC score drop from 2 or more points at baseline to 0 or 1 points during maintenance treatment.
Neurocrine reported that while TMC scores at baseline were comparable between groups, more participants in the Ingrezza group experienced potentially meaningful reductions in chorea for all affected body regions compared with those in the placebo group.
Average TMC scores dropped with treatment for all body regions, with numerically greater reductions seen with Ingrezza compared with the placebo.
Such reductions reached statistical significance for the upper and lower extremities, which were the most affected at study’s start, according to the company.
The ongoing open-label KINECT-HD2 trial (NCT04400331) is evaluating the long-term effects of Ingrezza in patients who completed KINECT-HD and other adults with Huntington’s-associated chorea. Interim data, covering nearly a year on Ingrezza, have demonstrated sustained reductions in chorea.
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