Chorea severity remains reduced after about 1 year on Ingrezza: Trial
Most participants report improvement in ongoing KINECT-HD2 Phase 3 trial
Nearly a year of treatment with Neurocrine Biosciences’ Ingrezza (valbenazine) leads to sustained reductions in uncontrolled movements known as chorea in adults with Huntington’s disease, according to interim data from a Phase 3 trial called KINECT-HD2.
“The 50-week data from the ongoing KINECT-HD2 study provide insight on the potential long-term use of Ingrezza for the management of chorea associated with Huntington’s disease,” Eiry Roberts, MD, Neurocrine’s chief medical officer, said in an email to Huntington’s Disease News.
“We look forward to analyzing additional data as they become available,” Roberts said in a company press release.
These and other Ingrezza-related trial findings were presented in a number of posters earlier this month at the 30th annual meeting of the Huntington Study Group in Phoenix.
A once-daily oral therapy, Ingrezza was approved in the U.S. a few months ago for chorea, the involuntary jerking or writhing movements that affect most people with Huntington’s. Neurocrine has stated Ingrezza is a more convenient option for controlling chorea than other available therapies.
Ingrezza’s approval was based largely on data from a Phase 3 clinical trial called KINECT-HD (NCT04102579), which tested the therapy against a placebo in more than 100 Huntington’s patients. Results indicated the therapy significantly outperformed a placebo in controlling chorea after about three months of treatment.
KINECT-HD2 trial collecting data on long-term safety, efficacy of Ingrezza
The ongoing KINECT-HD2 (NCT04400331) is collecting data on the long-term safety and efficacy of Ingrezza in 154 Huntington’s patients.
All participants are given Ingrezza at a maximum dose of 40 mg/day for two weeks, 60 mg/day for another two weeks, and 80 mg/day thereafter. The dose for each participant may be adjusted below these maximums based on tolerability and chorea severity.
The trial’s interim data, covering data collected through September 2022, were presented in the poster “Sustained Improvements with Once-Daily Valbenazine in Chorea Associated with Huntington’s Disease: Interim Results from a Long-Term Open-Label Study” (abstract #64).
At the time of the analysis, 127 patients had been recruited, 98 of whom had previously participated in the KINECT-HD study. Nearly all had completed the initial dose-increasing period, and more than half had been followed for at least 50 weeks (nearly a year).
Chorea severity is being tracked using the Total Maximal Chorea (TMC) score of the Unified Huntington’s Disease Rating Scale. It rates the severity of chorea, from 0 (absent) to 4 (prolonged), across seven different parts of the body. Scores for each body part are summed to get the total score.
Results showed the average TMC score decreased by 3.4 points after two weeks of Ingrezza treatment, and by 5.6 points by week eight. Available 50-week data showed the score was decreased by 5.8 points on average relative to the start of the study.
These results indicate “sustained improvement in chorea with one-capsule, once-daily Ingrezza from the first evaluation at Week 2 on the lowest dose of 40 mg through Week 50 at [a dose of up to] 80 mg,” Roberts said in the email.
Up to 4.5 months of data from six participants who were on stable-dose antipsychotic medications at the start of KINECT-HD2 showed a similar therapeutic efficacy of Ingrezza, with the average TMC score being reduced by 5.2 points at the latest assessment.
“Preliminary analyses suggest that these long-term effects of [Ingrezza] on chorea will be sustained regardless of concomitant antipsychotic treatment,” the scientists wrote.
More than half (60.9%) of patients said their condition had “much improved” or “very much improved” by six weeks, and nearly three-quarters (74.2%) reported such improvements at week 50. Clinicians also reported such improvements in similar proportions of patients (58.9% at week 6 and 76.9% at week 50).
KINECT-HD2 so far has not revealed any unexpected safety findings. The most commonly reported adverse events include falls (30.4%), sleepiness (24%), and fatigue (24%), which the researchers said are “consistent with symptoms common to HD [Huntington’s disease] … or similar to those reported in other [Ingrezza] clinical trials.”
“These interim data provide insight on the clinically meaningful and sustained improvements participants are experiencing with Ingrezza for the treatment of chorea,” Roberts said in the press release.
Sensors used to track chorea in trial participants on Ingrezza
Neurocrine also presented new KINECT-HD study analyses of data from never-before-used measures to track disease severity.
Data from a substudy where sensors worn on the body were used to track chorea in 27 trial participants were presented in the poster “A Wearable Movement Sensor Substudy of KINECT-HD, a Phase 3 Trial of Valbenazine for the Treatment of Chorea Associated with Huntington Disease” (abstract #65).
From the sensor data, the researchers calculated a truncal chorea index to quantify chorea severity in the trunk. Results showed the index score was significantly reduced by nearly two points after about three months of Ingrezza treatment, while it was essentially unchanged in patients given a placebo.
The sensor data also indicated Ingrezza helped to significantly reduce gait asymmetry, when the left and right side of the body aren’t balancing properly during walking.
Collectively, these data “augment the main study findings by showing improvements with [Ingrezza] in truncal chorea and gait asymmetry,” the researchers wrote.
Indirect comparision of Ingrezza with Austedo
In the poster “Indirect Treatment Comparison of Valbenazine with Deutetrabenazine for Improvement in Total Maximal Chorea Score in Huntington Disease” (abstract #62), researchers presented results of an indirect efficacy comparison between Ingrezza and Austedo, an older oral therapy approved for Huntington’s-related chorea.
They compared data from the KINECT-HD trial against those from the Phase 3 First-HD trial (NCT01795859) that supported Austedo’s approval. Both studies lasted 12 weeks (about three months) and compared the effects of treatment versus a placebo on the TMC.
Findings indicated Ingrezza-treated patients tended to report a significantly more profound reduction in chorea severity in the first two to four weeks of treatment. But from week six onwards, both therapies showed comparable effects on TMC scores.
Nevertheless, the researchers emphasized that indirect comparisons are by nature imperfect, as it’s impossible to fully account for differences between studies.
Neurocrine also recently announced it has settled all legal disputes resulting from companies that attempted to bring generic versions of Ingrezza to the market while the name-brand medication is still under patent protection.
As part of the resolution of the lawsuits, four undisclosed companies have secured the right to sell generic versions of the drug in the U.S. starting in March 2038 (or earlier in certain customary circumstances).
“These settlements reinforce our belief in the strength of the Ingrezza intellectual property estate and provide clarity regarding Ingrezza exclusivity,” Darin Lippoldt, Neurocrine’s chief legal officer, said in a separate company press release.