Valbenazine receives FDA approval for chorea associated with Huntington's disease

"We are proud to bring INGREZZA to people living with HD and their caregivers who now have the option of a one-capsule, once-daily treatment that has demonstrated significant improvement in HD chorea in clinical studies," said Kevin C. Gorman, Chief Executive Officer, of Neurocrine Biosciences. "We are thankful for those in the HD community who helped contribute to this important milestone, and we remain committed to bringing medicines to patients with unmet medical needs for debilitating neurological disorders."

Key clinical trial outcomes from KINECT-HD include:

• INGREZZA demonstrated a three-times greater improvement in chorea severity compared to placebo, with a 4.6-point improvement seen with INGREZZA versus a 1.4-point improvement with placebo in the chorea severity score from the start to the end of the 12-week clinical study (least squares mean difference –3.2, 95% CI, –4.4 to –2.0; P < 0.0001).1,2
• INGREZZA reduced chorea severity by about 40 percent from baseline to maintenance (P < 0.0001) and nearly half of patients saw a more than 40 percent reduction in HD chorea severity by Week 12.1,2
• Fifty-three percent of patients and 43 percent of healthcare professionals reported overall HD chorea symptoms were "very much improved" or "much improved" at Week 12.1,2

Like other FDA-approved treatments for chorea associated with HD, the prescribing information for INGREZZA now includes important safety information regarding serious risk, including depression and suicidal ideation and behavior in patients with Huntington'sdisease and Neuroleptic Malignant Syndrome (NMS).

In clinical studies in Huntington's disease, treatment-emergent adverse events included somnolence and sedation, urticaria, rash and insomnia.

See full Important Safety Information below.

"Clinical results that led to this important approval showed reduction in the severity of chorea as early as two weeks after starting INGREZZA at an initial dose of 40 mg, with consistently greater improvements versus placebo seen at all subsequent visits," said Erin Furr Stimming, M.D., FAAN, FANA, Principal Investigator, Huntington Study Group and Professor of Neurology, McGovern Medical, UTHealth Houston. "Data also demonstrated INGREZZA was generally well tolerated and showed clinically meaningful improvement in adults with chorea associated with HD."

"Chorea associated with HD can significantly affect the quality of life of a person living with HD by impacting their daily activities, social life, independence and overall well-being," said Louise Vetter, President and Chief Executive Officer of the Huntington's Disease Society of America. "The approval of INGREZZA for HD chorea means that people living with HD have a new treatment option to help manage their chorea symptoms, which is a welcomed milestone in efforts to improve care for families affected by HD."

The INBRACE® Support Program helps patients who are prescribed INGREZZA by assisting with product support and prescription fulfillment through a dedicated network of carefully selected specialty and local affiliated pharmacies. Patients with commercial insurance may be eligible for copay assistance and patients with no prescription coverage who also lack the financial resources to pay for their medicine may be eligible for participation in the patient assistance program. For more information, patients may visit INBRACESupportProgram.com/INGREZZAPatient/.

About Chorea Associated with Huntington's Disease (HD)

Huntington's disease (HD) is a hereditary progressive neurodegenerative disorder in which the loss of certain neurons within the brain causes motor, cognitive and psychiatric symptoms. Symptoms generally appear between the ages of 30 and 50 years and worsen over a 10- to 25-year period. Most people with HD experience chorea, an abnormal involuntary movement disorder, characterized by irregular and unpredictable movements. Chorea can affect various body parts and interfere with motor coordination, gait, swallowing and speech. HD is estimated to affect approximately 41,000 adults in the U.S., with more than 200,000 at risk of inheriting the disease.

About the KINECT®-HD Study

KINECT®-HD is a Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of valbenazine as a once-daily treatment to reduce chorea associated with Huntington's disease (HD) and evaluate the safety and tolerability of valbenazine in patients with HD. The study enrolled 128 adults 18 to 75 years of age who were diagnosed with motor-manifest HD and who had sufficient chorea symptoms to meet study protocol criteria.

KINECT-HD used the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score as the primary efficacy endpoint. The secondary endpoints included Clinical Global Impression of Change (CGI-C) response status and Patient Global Impression of Change (PGI-C) response status for valbenazine treatment. Treatment with valbenazine resulted in a placebo-adjusted mean reduction in the TMC score of 3.2 units (P < 0.0001), indicating a highly statistically significant improvement in chorea. Secondary endpoints of CGI-C response status and PGI-C response status were also statistically significant and supported the improvements in TMC score that were seen over the 12-week study period.

Treatment-emergent adverse events in this study were generally consistent with the known safety profile of valbenazine. No suicidal behavior or worsening of suicidal ideation were observed in the valbenazine-treated participants in this study.

View the complete study results from the Phase 3 KINECT-HD study published in The Lancet Neurology online edition. For more information on the KINECT-HD study, please visit HuntingtonStudyGroup.org.

About KINECT®-HD2

KINECT®-HD2 is an ongoing open-label study to evaluate the long-term safety and tolerability, as well as the maintenance of effects, of INGREZZA in patients with chorea associated with Huntington's disease (HD). The 156-week study will enroll more than 150 adults 18 to 75 years of age who have been diagnosed with motor-manifest HD and who have sufficient chorea symptoms to meet study protocol criteria. Concomitant antipsychotic use is allowed in the study. For more information on the KINECT-HD2 study, please visit Huntington StudyGroup.org or ClinicalTrials.gov.

About Huntington Study Group/HSG Clinical Research, Inc.

The Huntington Study Group (HSG), a not-for-profit organization founded in 1993 in Rochester, NY, and its wholly owned subsidiary, HSG Clinical Research, Inc., designs and conducts clinical trials through the world's first and largest collaborative network with thousands of members at more than 130 HSG credentialed research sites worldwide. HSG is dedicated to improving the lives of people impacted by Huntington's disease through research, education, and collaboration. For more information, visit HuntingtonStudyGroup.org.

The KINECT-HD study was conducted in cooperation with the HSG and the Clinical Trials Coordination Center (CTCC) at the University of Rochester Medical Center's Center for Health + Technology (CHeT). For more information, visiturmc.Rochester.edu/Health-Technology/Our-Expertise/Clinical-Trials-Coordination.aspx.

About INGREZZA® (valbenazine) Capsules

INGREZZA is the only one-capsule, once-daily selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington's disease (HD).

INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA selectively targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements. Additionally, INGREZZA can be taken for the treatment of tardive dyskinesia as one-capsule once-daily, together with most psychiatric medications such as antipsychotics or antidepressants. INGREZZA dosages approved for use are 40 mg, 60 mg and 80 mg capsules. INGREZZA is not approved in any other dosage form.