AAN 2024: Ingrezza eases chorea, regardless of antipsychotics use

Benefits sustained for up to 1 year for patients overall in KINECT-HD2 trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Daily treatment with Ingrezza (valbenazine) led to sustained reductions in chorea — characterized by involuntary, unpredictable body movements — for nine months among the small group of Huntington’s disease patients simultaneously using antipsychotic medications in the Phase 3 KINECT-HD2 trial.

In addition, improvements in chorea were also sustained for up to a year of the oral therapy, developed by Neurocrine Biosciences, among the overall trial population, as previously reported.

Those were the findings presented by the study’s principal investigator, Erin Furr-Stimming, MD, of the University of Texas Health Science Center – Houston, in a talk at the recent American Academy of Neurology (AAN) 2024 Annual Meeting.

The presentation was titled “Sustained Improvements with Once-daily Valbenazine in Chorea Associated with Huntington’s Disease: Interim Results from a Long-term Open-label Study.”

“These interim long-term data results suggest clinically meaningful and sustained improvements in chorea for participants taking Ingrezza regardless of concomitant [simultaneous] antipsychotic therapy,” Eiry W. Roberts, MD, Neurocrine’s chief medical officer, said in an emailed statement to Huntington’s Disease News. “We look forward to sharing additional future analyses on these important data.”

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Ingrezza approved last year in US for Huntington’s-associated chorea

Ingrezza was approved in the U.S. last year for adults with Huntington’s-associated chorea — the involuntary movements that affect most people with the neurodegenerative disease.

That clearance was backed mainly by findings from the Phase 3 KINECT-HD clinical trial (NCT04102579), where Ingrezza led to better chorea control than a placebo over about three months of treatment.

Some of the participants went on to enroll in the ongoing open-label KINECT-HD2 study (NCT04400331), which is looking at Ingrezza’s long-term safety and efficacy in adults, ages 18-75, with Huntington’s-associated troublesome chorea.

Patients are first treated in a two-month dose-adjustment phase, where the daily dose is gradually increased from 40 mg up to a target dose of 80 mg. The maximum tolerated dose up to 80 mg is then continued for up to nearly three more years.

While simultaneous use of stable antipsychotic medications hadn’t been allowed in KINECT-HD, it was permitted in KINECT-HD2.

At the AAN meeting, Furr-Stimming discussed up to about a year’s worth of data from 125 KINECT-HD2 participants who had received at least one dose of Ingrezza, 98 of whom had participated in the previous trial.

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Ingrezza study shows sustained reductions in chorea severity up to 1 year

As previously reported, results showed sustained reductions in chorea severity up to a year of treatment, as assessed by the Total Maximal Chorea (TMC) score of the Unified Huntington’s Disease Rating Scale (UHDRS). The higher the TMC score, the worse the chorea.

“Improvements were observed as early as week 2, when participants were taking 40 mg,” Furr-Stimming said.

Mean TMC scores had dropped by 5.6 points at the end of the dose-adjustment period, and by 5.8 points after a year, at which time 66 participants remained on treatment.

In a subgroup of 10 participants who were also on a stable regimen of antipsychotic medications at the start of the study, the benefits were “similar to the improvements found in the overall population,” Furr-Stimming said.

TMC scores in that group dropped by a mean of 5.1 points by the end of the dose-adjustment period, and these improvements were sustained, with a mean drop of 5.8 points, for up to about nine months in the four patients who remained in the study.

I am grateful to at least have another effective treatment option when and if chorea needs to be suppressed to give our patients some relief from this devastating disease.

Most patients, clinicians rated chorea as improved, very much improved

About three-quarters of the patients and clinicians across the entire study population rated chorea as much or very much improved (reduced) — indicators of a treatment response — after a year.

Ingrezza was overall safe, with the most common side effects being fall, sleepiness, and fatigue. About 14% of participants discontinued treatment due to adverse events, mostly due to fatigue and anxiety, according to Furr-Stimming.

“For those of us that have the privilege of caring for patients and families with Huntington’s disease, we know that chorea is only one of the many symptoms that our patients experience,” Furr-Stimming said.

“However, I am grateful to at least have another effective treatment option when and if chorea needs to be suppressed to give our patients some relief from this devastating disease,” she added.

Neurocrine also presented findings from a substudy of the earlier KINECT-HD trial in a poster, titled “A Wearable Movement Sensor Substudy of KINECT-HD, a Phase 3 Trial of Valbenazine for the Treatment of Chorea Associated with Huntington’s Disease.”

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Substudy evaluated use of wearable sensors to track disease severity

The substudy was designed to evaluate the use of wearable sensors to track disease severity in Huntington’s patients as a way of supplementing clinician-rated measures like the UHDRS.

A group of 27 KINECT-HD participants wore the sensors — placed on the chest and each thigh — at home for at least five hours per day during a one-week period before receiving Ingrezza, and again during a one-week period during treatment.

Data collected from the sensors were analyzed to look at chorea and parameters of gait asymmetry, when the left and right side of the body aren’t balancing properly during walking.

Consistent with the study’s main findings, Ingrezza was associated with significant reductions in chorea in the body’s trunk and significant improvements in all gait asymmetry parameters relative to a placebo based on the sensor analysis.

Six patients had a sensor-related adverse event, all of which were mild. Skin irritation led to sensor removal in one patient.

This substudy “not only reinforces the efficacy seen in in the KINECT-HD trial, but also supports further exploration of the use of digital measures in clinical trials,” Roberts said. “These findings will ultimately … improve clinical research and care for individuals with [Huntington’s disease].”