Neurocrine Biosciences Presents Interim Data Demonstrating Robust and Sustained Improvements in Chorea Associated With Huntington's Disease Through Week 104 Irrespective of Antipsychotic Use
Neurocrine Biosciences (Nasdaq: NBIX) presented interim results from the KINECT®-HD2 study of INGREZZA® (valbenazine) for treating chorea in Huntington's disease. The study showed robust and sustained improvements in chorea through Week 104, regardless of antipsychotic use. Key findings include:
- Improved chorea as early as Week 2 (-3.4 TMC score change) with 40 mg dose
- Sustained efficacy from Week 8 (-5.7) to Week 104 (-5.2) with up to 80 mg dose
- Over 50% of participants rated symptoms as 'much improved' or 'very much improved' from Week 6 onwards
- At Week 104, 75.9% of participants self-reported improvement, with 73.6% clinician-assessed improvement
The most common side effects were falls, somnolence, and fatigue. This study is significant as it's the first to include patients taking antipsychotics in a VMAT2 inhibitor trial for Huntington's disease chorea.
Neurocrine Biosciences (Nasdaq: NBIX) ha presentato risultati intermedi dello studio KINECT®-HD2 su INGREZZA® (valbenazina) per il trattamento della corea nella malattia di Huntington. Lo studio ha mostrato miglioramenti significativi e sostenuti nella corea fino alla Settimana 104, indipendentemente dall'uso di antipsicotici. I risultati principali includono:
- Miglioramenti della corea già dalla Settimana 2 (cambiamento del punteggio TMC di -3.4) con dose da 40 mg
- Efficacia sostenuta dalla Settimana 8 (-5.7) fino alla Settimana 104 (-5.2) con dose fino a 80 mg
- Oltre il 50% dei partecipanti ha valutato i sintomi come 'migliorati notevolmente' o 'migliorati molto' dalla Settimana 6 in poi
- Alla Settimana 104, il 75.9% dei partecipanti ha riportato un miglioramento, con il 73.6% di miglioramento valutato dai clinici
Effetti collaterali più comuni sono stati cadute, sonnolenza e affaticamento. Questo studio è significativo poiché è il primo a includere pazienti in trattamento con antipsicotici in un trial di inibitori VMAT2 per la corea della malattia di Huntington.
Neurocrine Biosciences (Nasdaq: NBIX) presentó resultados interinos del estudio KINECT®-HD2 de INGREZZA® (valbenazina) para el tratamiento de la corea en la enfermedad de Huntington. El estudio mostró mejoras sólidas y sostenidas en la corea hasta la Semana 104, sin importar el uso de antipsicóticos. Los hallazgos clave incluyen:
- Mejora de la corea ya en la Semana 2 (cambio en la puntuación TMC de -3.4) con una dosis de 40 mg
- Eficacia sostenida desde la Semana 8 (-5.7) hasta la Semana 104 (-5.2) con dosis de hasta 80 mg
- Más del 50% de los participantes calificaron los síntomas como 'muy mejorados' o 'realmente muy mejorados' desde la Semana 6 en adelante
- En la Semana 104, el 75.9% de los participantes se autoinformaron sobre una mejora, con un 73.6% de mejora evaluada por los clínicos
Los efectos secundarios más comunes fueron caídas, somnolencia y fatiga. Este estudio es significativo ya que es el primero en incluir pacientes en tratamiento con antipsicóticos en un ensayo de inhibidores de VMAT2 para la corea de la enfermedad de Huntington.
뉴로크라인 바이오사이언스(Nasdaq: NBIX)가 헌팅턴병의 혼동 증상 치료를 위한 INGREZZA®(발베나진) KINECT®-HD2 연구의 중간 결과를 발표했습니다. 이 연구는 104주차까지 혼동 증상에서 강력하고 지속적인 개선을 나타냈습니다, 항정신병약 사용과 관계없이. 주요 발견 사항은 다음과 같습니다:
- 2주차부터 시작된 혼동 증상 개선 (-3.4 TMC 점수 변화) 40mg 용량
- 8주차 (-5.7)에서 104주차 (-5.2)까지의 지속적인 효능, 최대 80mg 용량
- 50% 이상의 참가자가 6주차부터 증상을 '많이 개선됨' 또는 '매우 많이 개선됨'으로 평가
- 104주차에 75.9%의 참가자가 자기보고한 개선, 73.6%의 임상 평가 개선
가장 일반적인 부작용은 낙상, 졸음 및 피로였습니다. 이 연구는 헌팅턴병 혼동 증상을 위한 VMAT2 억제제 임상 시험에서 항정신병약을 복용하는 환자를 포함한 최초의 연구로 중요합니다.
Neurocrine Biosciences (Nasdaq: NBIX) a présenté des résultats intermédiaires de l'étude KINECT®-HD2 concernant INGREZZA® (valbénazine) pour le traitement de la chorée dans la maladie de Huntington. L'étude a montré des améliorations significatives et durables de la chorée jusqu'à la Semaine 104, quel que soit l'utilisation d'antipsychotiques. Les principales conclusions incluent :
- Amélioration de la chorée dès la Semaine 2 (changement de score TMC de -3.4) avec une dose de 40 mg
- Efficacité soutenue de la Semaine 8 (-5.7) à la Semaine 104 (-5.2) avec une dose allant jusqu'à 80 mg
- Plus de 50 % des participants ont évalué les symptômes comme 'beaucoup améliorés' ou 'très améliorés' à partir de la Semaine 6
- À la Semaine 104, 75.9 % des participants ont déclaré une amélioration, avec une amélioration évaluée par les cliniciens de 73.6 %
Les effets secondaires les plus courants étaient des chutes, de la somnolence et de la fatigue. Cette étude est significative car elle est la première à inclure des patients prenant des antipsychotiques dans un essai d'inhibiteurs de VMAT2 pour la chorée de la maladie de Huntington.
Neurocrine Biosciences (Nasdaq: NBIX) präsentierte vorläufige Ergebnisse der KINECT®-HD2-Studie zu INGREZZA® (Valbenazin) zur Behandlung der Chorea bei Huntington-Krankheit. Die Studie zeigte starke und nachhaltige Verbesserungen der Chorea bis Woche 104, unabhängig von der Verwendung von Antipsychotika. Zu den wesentlichen Ergebnissen gehören:
- Verbesserung der Chorea bereits in Woche 2 (Änderung des TMC-Werts von -3.4) mit einer Dosis von 40 mg
- Nachhaltige Wirksamkeit von Woche 8 (-5.7) bis Woche 104 (-5.2) mit bis zu 80 mg Dosis
- Über 50% der Teilnehmer bewerteten die Symptome als 'deutlich verbessert' oder 'sehr stark verbessert' ab Woche 6
- In Woche 104 berichteten 75.9% der Teilnehmer über eine Verbesserung, wobei 73.6% von Kliniker bewertet wurden
Die häufigsten Nebenwirkungen waren Stürze, Schläfrigkeit und Müdigkeit. Diese Studie ist bedeutend, da sie die erste ist, die Patienten, die Antipsychotika einnehmen, in eine VMAT2-Hemmer-Studie zur Chorea bei Huntington-Krankheit einbezieht.
- Sustained improvement in chorea symptoms through Week 104
- Efficacy demonstrated regardless of antipsychotic use
- Rapid onset of action with improvements seen as early as Week 2
- High percentage of patients (>75%) reporting significant improvement at Week 104
- Consistent safety profile with previous KINECT-HD study
- Common side effects include falls, somnolence, and fatigue
Insights
This interim data from the KINECT-HD2 study demonstrates significant and sustained improvements in chorea symptoms associated with Huntington's disease (HD) over a 104-week period using INGREZZA (valbenazine). Key findings include:
- Rapid improvement in chorea symptoms starting at Week 2
- Sustained efficacy through Week 104 with maintenance dosing
- Consistent benefits regardless of concomitant antipsychotic use
- High response rates (>
70% ) at Week 104 based on both patient and clinician assessments
The safety profile appears consistent with previous studies, with falls, somnolence and fatigue as common side effects. This long-term data is particularly valuable for HD patients, as it suggests INGREZZA can provide durable symptom relief without interfering with antipsychotic treatments often used for neuropsychiatric symptoms. The study's inclusion of patients on antipsychotics addresses a significant gap in previous VMAT2 inhibitor trials for HD chorea.
While this study doesn't provide direct financial metrics, the positive long-term efficacy and safety data for INGREZZA in Huntington's disease chorea could significantly impact Neurocrine Biosciences' market position and future revenue streams. Key financial implications include:
- Potential expansion of INGREZZA's approved indications, broadening its market reach
- Increased confidence in long-term use may drive higher prescription rates and patient adherence
- Compatibility with antipsychotics could make INGREZZA a preferred choice for many HD patients
- Sustained efficacy over 104 weeks suggests potential for long-term revenue generation per patient
Investors should monitor for potential FDA submissions based on this data and any changes in sales forecasts for INGREZZA. The
- KINECT®-HD2 Is the First Prospective Clinical Trial to Include Patients Taking Antipsychotic Medication in a Study Evaluating a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor for the Treatment of Huntington's Disease Chorea
- Findings Presented at the 2024 MDS International Congress of Parkinson's Disease and Movement Disorders®
"The data from this study reinforce the long-term clinical safety of INGREZZA observed to date, showing sustained improvement in chorea regardless of antipsychotic use during the study," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "This is an important finding given that approximately a third of patients living with Huntington's disease chorea are prescribed antipsychotic medications for neuropsychiatric symptoms without receiving treatment for the chorea that may significantly disrupt daily life."
The effect of INGREZZA on chorea over time was assessed using mean changes from baseline in the Unified Huntington's Disease Rating Scale Total Maximal Chorea (TMC) score and response status ("much improved" or "very much improved") for Clinical Global Impression of Change and Patient Global Impression of Change.
Data from this interim analysis of KINECT-HD2 suggest robust and sustained improvements in Huntington's disease (HD) chorea with INGREZZA treatment:
- INGREZZA improved HD chorea as early as Week 2 (TMC change from baseline: -3.4) at the starting dose of 40 mg and at Week 4 (-4.6) with doses up to 60 mg. Efficacy was sustained from Week 8 (-5.7) to Week 104 (-5.2) at the maintenance dose of up to 80 mg.
- These improvements were consistent regardless of presence or absence of concomitant antipsychotic treatment.
- At Week 6 and at each visit thereafter, more than half of participants and investigators rated symptoms as "much improved" or "very much improved." At Week 104, this response status was achieved in
75.9% of participants based on self-report and73.6% of participants based on clinician assessment. - The most common treatment-emergent adverse events at the time of the analysis were consistent with those observed in KINECT-HD, including falls, somnolence and fatigue.
Additional presentations by Neurocrine Biosciences include:
- Somnolence-Related Events Over Time with Valbenazine Treatment for Chorea Associated with Huntington's Disease (Poster #1445)
- Treatment Effect Sizes of Once-Daily Valbenazine for Tardive Dyskinesia and for Chorea Associated with Huntington's Disease: A Post-Hoc Analysis of Phase 3 Clinical Trial Data (Poster #1466)
About Chorea Associated with Huntington's Disease
Huntington's disease 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 KINECT®-HD
KINECT®-HD was 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 substantial 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. The most common adverse reactions in patients with HD included somnolence and sedation, urticaria, rash and insomnia.
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 maintenance period up to week 156 of treatment enrolled 154 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 HuntingtonStudyGroup.org or ClinicalTrials.gov.
About INGREZZA® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules
INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the
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 is unique in that it selectively and specifically 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.
INGREZZA can be taken as one capsule, once daily together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA® SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules.
Important Information
Approved Uses
INGREZZA® (valbenazine) capsules or INGREZZA® SPRINKLE (valbenazine) capsules are prescription medicines used to treat adults with:
- movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia).
- involuntary movements (chorea) of Huntington's disease. INGREZZA or INGREZZA SPRINKLE do not cure the cause of involuntary movements, and do not treat other symptoms of Huntington's disease, such as problems with thinking or emotions.
It is not known if INGREZZA or INGREZZA SPRINKLE is safe and effective in children.
IMPORTANT SAFETY INFORMATION
INGREZZA or INGREZZA SPRINKLE can cause serious side effects in people with Huntington's disease, including: depression, suicidal thoughts, or suicidal actions. Tell your healthcare provider before you start taking INGREZZA or INGREZZA SPRINKLE if you have Huntington's disease and are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when INGREZZA or INGREZZA SPRINKLE is started and when the dose is changed. Call your healthcare provider right away if you become depressed, have unusual changes in mood or behavior, or have thoughts of hurting yourself.
Do not take INGREZZA or INGREZZA SPRINKLE if you:
- are allergic to valbenazine, or any of the ingredients in INGREZZA or INGREZZA SPRINKLE.
INGREZZA or INGREZZA SPRINKLE can cause serious side effects, including:
- Allergic reactions. Allergic reactions, including an allergic reaction that causes sudden swelling called angioedema can happen after taking the first dose or after many doses of INGREZZA or INGREZZA SPRINKLE. Signs and symptoms of allergic reactions and angioedema include: trouble breathing or shortness of breath, swelling of your face, lips, eyelids, tongue, or throat, or other areas of your skin, trouble with swallowing, or rash, including raised, itchy red areas on your skin (hives). Swelling in the throat can be life-threatening and can lead to death. Stop taking INGREZZA or INGREZZA SPRINKLE and go to the nearest emergency room right away if you develop these signs and symptoms of allergic reactions and angioedema.
- Sleepiness and tiredness that could cause slow reaction times (somnolence and sedation). Do not drive a car or operate dangerous machinery until you know how INGREZZA or INGREZZA SPRINKLE affects you. Drinking alcohol and taking other medicines may also cause sleepiness during treatment with INGREZZA or INGREZZA SPRINKLE.
- Heart rhythm problems (QT prolongation). INGREZZA or INGREZZA SPRINKLE may cause a heart rhythm problem known as QT prolongation. You have a higher chance of getting QT prolongation if you also take certain other medicines during treatment with INGREZZA or INGREZZA SPRINKLE. Tell your healthcare provider right away if you develop any signs or symptoms of QT prolongation, including: fast, slow, or irregular heartbeat (heart palpitations), shortness of breath, dizziness or lightheadedness, or fainting or feeling like you are going to faint.
- Neuroleptic Malignant Syndrome (NMS). NMS is a serious condition that can lead to death. Call a healthcare provider right away or go to the nearest emergency room if you develop these symptoms and they do not have another obvious cause: high fever, stiff muscles, problems thinking, irregular pulse or blood pressure, increased sweating, or very fast or uneven heartbeat.
- Parkinson-like symptoms. Symptoms include: body stiffness, drooling, trouble moving or walking, trouble keeping your balance, shaking (tremors), or falls.
Before taking INGREZZA or INGREZZA SPRINKLE, tell your healthcare provider about all of your medical conditions including if you: have liver or heart problems, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Make sure you tell all of your healthcare providers that you are taking INGREZZA or INGREZZA SPRINKLE. Taking INGREZZA or INGREZZA SPRINKLE with certain other medicines may cause serious side effects. Especially tell your healthcare provider if you: take digoxin or take or have taken a monoamine oxidase inhibitor (MAOI) medicine. You should not take INGREZZA or INGREZZA SPRINKLE if you are taking, or have stopped taking, a MAOI within the last 14 days.
The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with tardive dyskinesia are sleepiness and tiredness.
The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with chorea associated with Huntington's disease include sleepiness and tiredness, raised itchy red areas on your skin (hives), rash, and trouble getting to sleep or staying asleep.
These are not all of the possible side effects of INGREZZA or INGREZZA SPRINKLE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at https://www.fda.gov/medwatch or call 1-800-FDA-1088.
Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules.
Please see full Prescribing Information, including Boxed Warning, and Medication Guide.
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter) and Facebook. (*in collaboration with AbbVie)
The NEUROCRINE BIOSCIENCES Logo Lockup, NEUROCRINE, YOU DESERVE BRAVE SCIENCE, KINECT and INGREZZA are registered trademarks of Neurocrine Biosciences, Inc.
Forward-Looking Statements
In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from INGREZZA for the treatment of chorea associated with Huntington's disease (HD) and the value INGREZZA may bring to patients with chorea associated with HD. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of INGREZZA for the treatment of chorea associated with HD; whether INGREZZA receives adequate reimbursement from third-party payors; the degree and pace of market uptake of INGREZZA for the treatment of chorea associated with HD; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA for the treatment of chorea associated with HD; risks associated with the Company's dependence on third parties for development and manufacturing activities related to INGREZZA for the treatment of chorea associated with HD, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for INGREZZA for the treatment of chorea associated with HD or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding INGREZZA for the treatment of chorea associated with HD; risks that post-approval INGREZZA commitments or requirements may be delayed; risks that INGREZZA for the treatment of chorea associated with HD may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA for the treatment of chorea associated with HD; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law.
© 2024 Neurocrine Biosciences, Inc. All Rights Reserved.
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FAQ
What were the main findings of the KINECT-HD2 study for INGREZZA in treating Huntington's disease chorea?
How does INGREZZA (valbenazine) affect the Unified Huntington's Disease Rating Scale Total Maximal Chorea (TMC) score?
What percentage of participants in the KINECT-HD2 study reported improvement in Huntington's disease chorea symptoms at Week 104?
What are the most common side effects of INGREZZA (valbenazine) reported in the KINECT-HD2 study for Huntington's disease chorea?
