Ingrezza treatment eases disease burden due to Huntington’s chorea
New data analyses from Phase 3 clinical trial show motor, cognitive gains
Daily treatment with Ingrezza (valbenazine) led to reductions in motor- and cognitive-related disease burden for adults with chorea due to Huntington’s disease, according to new data analyses from the Phase 3 KINECT-HD clinical trial.
These changes were assessed with a relatively new patient-reported measure, called the Huntington’s Disease Health Index (HD-HI), which covers five domains: cognitive function, mobility/ambulation, abnormal movements, hand/arm function, and gastrointestinal health.
The new findings were presented at the Advanced Therapeutics in Movement & Related Disorders Congress, held recently in Washington D.C.
Top-line data from KINECT-HD (NCT04102579) had previously shown “Ingrezza’s ability to significantly reduce chorea, one of the most visible and disruptive symptoms of Huntington’s disease, which often occurs alongside cognitive decline and leads to serious motor challenges,” Sanjay Keswani, MD, chief medical officer at Neurocrine Biosciences, Ingrezza’s developer, said in a company press release. “These new patient-reported analyses highlight Ingrezza’s ability to reduce additional cognitive- and motor-related challenges faced by those living with Huntington’s disease, including memory loss, limitations with mobility, and trouble swallowing.”
This makes KINECT-HD the first and only trial to demonstrate measurable changes in cognitive- and motor-related disease burden with a vesicular monoamine transporter 2 (VMAT2) inhibitor — the class of medications to which Ingrezza belongs — according to Neurocrine.
Ingrezza treatment linked to reductions in chorea severity
Chorea, characterized by involuntary and uncontrollable jerky movements, is among the most common Huntington’s symptoms. This manifestation is thought to be linked to unusually high levels of a brain-signaling molecule called dopamine.
Ingrezza works by blocking the activity of the VMAT2 protein that’s involved in dopamine transport and recycling. The therapy is believed to reduce the amount of dopamine released from nerve cells, thereby easing chorea.
Taken as oral capsules swallowed whole, Ingrezza was approved in the U.S. in 2023 for adults with Huntington’s-associated chorea. An oral granulated formulation that can be sprinkled on food, called Ingrezza Sprinkle, was approved the following year.
Ingrezza’s approval for Huntington’s chorea was backed by data from KINECT-HD, which enrolled 128 adults, ages 18 to 75, with Huntington’s chorea. They were randomly assigned to receive either Ingrezza or a placebo once daily for 12 weeks, or about three months.
Trial results showed that Ingrezza treatment was associated with significant reductions in chorea severity compared with the placebo, as assessed by the Total Maximal Chorea score on the Unified Huntington’s Disease Rating Scale.
Disease burden reduced across nearly all cognitive, motor items
KINECT-HD was the first trial to employ HD-HI, which was the focus of the recent post-hoc analyses that occurred after the study was concluded. The measure includes 127 items, representing 13 symptomatic themes, or subscales.
Scores on all subscales, as well as the total score, range from 0 to 100, with higher values reflecting greater disease burden.
Score changes were assessed between the study’s start, or baseline, and maintenance dosing, which occurred during weeks 10 to 12 of treatment. Participants were included in the analysis if they were considered affected by those symptoms at baseline, reflected by a score of at least two on a given item of the HD-HI.
Previously reported data showed Ingrezza-treated patients reported greater score reductions on eight of the 13 HD-HI domains. The newly announced results provided more detailed changes across HD-HI items.
Specifically, Ingrezza was associated with larger score reductions than the placebo across all 18 cognition items and 32 of 33 motor items that were assessed. A number of these differences reached statistical significance, including the cognitive items of memory loss, reduced decision-making abilities, and trouble finding the right words.
Motor-related items that reached statistical significance included limitations with mobility/walking, abnormal movements, impaired coordination, hard time sitting still, problems knocking things over, and swallowing problems.
People completing KINECT-HD, as well as additional Huntington’s patients with chorea, could choose to enter an ongoing extension study called KINECT-HD2 (NCT04400331) that is evaluating the long-term safety and efficacy of Ingrezza. Initial data indicated the therapy’s benefits are sustained for nearly a year.
Neurocrine presented additional long-term data at the recent conference, as well as data on the effects of Ingrezza in people with tardive dyskinesia, another movement disorder for which the therapy is approved.
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