#AAN2022 – Valbenazine Quickly Eases Chorea in KINECT-HD Trial
Treatment with oral valbenazine, a dopamine-modulating medicine, significantly eased the jerky, involuntary movements of chorea after as little as two weeks for Huntington’s disease patients in a completed Phase 3 clinical trial.
More study participants given valbenazine also reported an improvement in their overall health status than did those randomized to a placebo.
These trial findings were presented at the American Academy of Neurology (AAN) annual meeting held earlier this month in Seattle.
Neurocrine Biosciences, the company that sells valbenazine, plans to apply to the U.S. Food and Drug Administration (FDA) this year for approval of the therapy to treat Huntington’s-associated chorea. Under the brand name Ingrezza, valbenazine is approved by the FDA for tardive dyskinesia, a movement disorder characterized by uncontrolled facial tics.
“Presentation of these positive data of valbenazine for chorea in Huntington disease represent a major step forward in our commitment to offering the community a potential new treatment option,” Eiry Roberts, MD, the company’s chief medical officer, said in a press release.
Neurocrine sponsored a Phase 3 clinical trial called KINECT-HD (NCT04102579) that enrolled 128 adults with Huntington’s marked by chorea. Participants were randomly assigned to valbenazine or a placebo capsule, taken daily for 12 weeks (about three months).
Top-line trial results, announced late last year, showed that treatment with valbenazine significantly eased chorea symptoms. Compared to patients on placebo, those given valbenazine reported a significant decrease of 3.2 units on the Total Maximal Chorea of the Unified Huntington’s Disease Rating Scale (UHDRS), a standard measure of the symptom’s severity.
Improvements in this score were seen as early as two weeks after starting treatment with valbenazine, and scores improved in both dose-adjustment and maintenance periods, Neurocrine reported.
Data presented at AAN concerned secondary goals on the Patient Global Impression of Change (PGI-C), a patient-reported measure of health status.
Findings showed the proportion of trial participants classified as “responders” — those reporting to be either “much improved” or “very much improved” since starting in the trial — was higher among patients given valbenazine than placebo (42.9% vs. 13.2%) after 12 weeks. These responses were also observed as early as two weeks after treatment.
The Clinical Global Impression of Change (CGI-C), a similar measure that assesses clinician-reported outcomes, showed a similar difference in “responder” rates favoring valbenazine at week 12 (52.7 vs. 26.4%). These favorable response rates were observed by doctors as early as four weeks after treatment.
Upper and lower limb physical function, assessed with a standard test called Neuro-QoL, did not differ significantly between patients on valbenazine or placebo.
Safety data in KINECT-HD were generally consistent with the known safety profile of valbenazine. The medication’s most common side effects include sleepiness, fatigue, fall, and akathisia (unprovoked feelings of agitation or restlessness). None of the valbenazine-treated participants reported any worsening of suicidal ideation or suicidal behavior.
“We are pleased with this data readout and are grateful to the patients and collaborators who have helped to advance this potential treatment,” said Andrew Feigin, MD, chair of the Huntington Study Group that helped run the KINECT-HD study.
Full data from KINECT-HD will be published in a peer-reviewed journal later this year, Neurocrine stated.
“Data from the KINECT-HD and the ongoing KINECT-HD2 study will form the basis of our supplemental new drug application (sNDA) for submission to the U.S. Food and Drug Administration later this,” Roberts said.
Neurocrine is sponsoring an open-label extension trial called KINECT-HD2 (NCT04400331), which is evaluating the long-term safety and effectiveness of valbenazine in Huntington’s. KINECT-HD2 is enrolling participants who completed the original KINECT-HD study, as well as other adults with Huntington’s and chorea at sites in the U.S. and Canada.
“We remain committed to this patient community as we look to further our scientific understanding of the efficacy and safety of valbenazine for chorea associated with Huntington disease in the long-term trial,” Feigin said.
Note: The Huntington’s Disease News team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting.