Intra-Cellular Therapies Presents Data from the CAPLYTA Adjunctive MDD Phase 3 Program at the American College of Neuropsychopharmacology Annual Meeting
Intra-Cellular Therapies presented data from its Phase 3 program for CAPLYTA (lumateperone) as adjunctive therapy for Major Depressive Disorder (MDD) at the American College of Neuropsychopharmacology Annual Meeting. The data from Studies 501 and 502 showed significant improvements in remission and response rates, as well as anxiety symptoms, with CAPLYTA compared to placebo. Specifically, Study 501 showed a response rate of 45.6% vs. 24.0% for placebo, and a remission rate of 25.9% vs. 13.6% for placebo. Study 502 reported a response rate of 40.1% vs. 25.3% for placebo, and a remission rate of 25.0% vs. 13.5% for placebo. Additionally, a post-hoc analysis from Study 403 indicated that CAPLYTA significantly improved anhedonia symptoms in patients with MDD and bipolar depression with mixed features.
Pooled safety data from Studies 501 and 502 confirmed a favorable safety profile, with common adverse reactions including dizziness, dry mouth, somnolence, nausea, and fatigue. CAPLYTA also showed low risks of extrapyramidal and motor symptoms.
Intra-Cellular Therapies ha presentato dati dal suo programma di Fase 3 per CAPLYTA (lumateperone) come terapia aggiuntiva per il Disturbo Depressivo Maggiore (MDD) durante l'Incontro Annuale del Collegio Americano di Neuropsicofarmacologia. I dati degli Studi 501 e 502 hanno mostrato miglioramenti significativi nei tassi di remissione e risposta, oltre ai sintomi di ansia, con CAPLYTA rispetto al placebo. In particolare, lo Studio 501 ha mostrato un tasso di risposta del 45,6% contro il 24,0% del placebo, e un tasso di remissione del 25,9% contro il 13,6% del placebo. Lo Studio 502 ha riportato un tasso di risposta del 40,1% contro il 25,3% del placebo, e un tasso di remissione del 25,0% contro il 13,5% del placebo. Inoltre, un'analisi post-hoc dello Studio 403 ha indicato che CAPLYTA ha migliorato significativamente i sintomi di anedonia nei pazienti con MDD e depressione bipolare con caratteristiche miste.
I dati di sicurezza aggregati degli Studi 501 e 502 hanno confermato un profilo di sicurezza favorevole, con reazioni avverse comuni che includono vertigini, secchezza delle fauci, sonnolenza, nausea e affaticamento. CAPLYTA ha anche mostrato un basso rischio di sintomi extrapiramidali e motori.
Intra-Cellular Therapies presentó datos de su programa de Fase 3 para CAPLYTA (lumateperona) como terapia adjunta para el Trastorno Depresivo Mayor (MDD) en la Reunión Anual del Colegio Americano de Neuropsicofarmacología. Los datos de los Estudios 501 y 502 mostraron mejoras significativas en las tasas de remisión y respuesta, así como en los síntomas de ansiedad, con CAPLYTA en comparación con el placebo. Específicamente, el Estudio 501 mostró una tasa de respuesta del 45,6% frente al 24,0% del placebo, y una tasa de remisión del 25,9% frente al 13,6% del placebo. El Estudio 502 reportó una tasa de respuesta del 40,1% frente al 25,3% del placebo, y una tasa de remisión del 25,0% frente al 13,5% del placebo. Además, un análisis post-hoc del Estudio 403 indicó que CAPLYTA mejoró significativamente los síntomas de anhedonia en pacientes con MDD y depresión bipolar con características mixtas.
Los datos de seguridad agrupados de los Estudios 501 y 502 confirmaron un perfil de seguridad favorable, con reacciones adversas comunes que incluyen mareos, boca seca, somnolencia, náuseas y fatiga. CAPLYTA también mostró bajo riesgo de síntomas extrapiramidales y motores.
인트라셀룰라 테라피스는 CAPLYTA (루마테페론)를 주요 우울 장애(MDD)의 보조 치료제로서 3상 프로그램 데이터를 미국 신경정신약리학회 연례 회의에서 발표했습니다. 연구 501과 502의 데이터는 CAPLYTA가 위약에 비해 관해 및 반응률, 불안 증상에서 유의미한 개선 효과를 나타냈습니다. 특히 연구 501에서는 반응률이 45.6%로 위약의 24.0%에 비해 높았고, 관해율은 25.9%로 위약의 13.6%보다 높았습니다. 연구 502에서는 반응률이 40.1%로 위약의 25.3%에 비해 높았고, 관해율은 25.0%로 위약의 13.5%보다 높았습니다. 또한, 연구 403의 후속 분석에서는 CAPLYTA가 MDD 및 혼합 특성을 가진 양극성 우울증 환자에서 무쾌감 증상을 유의미하게 개선한 것으로 나타났습니다.
연구 501과 502의 통합 안전성 데이터는 흔한 부작용으로 어지러움, 구강 건조, 졸림, 메스꺼움 및 피로를 포함하여 긍정적인 안전성 프로필을 확인했습니다. CAPLYTA는 또한 이상운동증 및 운동 증상에 대한 낮은 위험을 보였습니다.
Intra-Cellular Therapies a présenté des données de son programme de Phase 3 pour CAPLYTA (lumateperone) en tant que thérapie adjuvante pour le trouble dépressif majeur (MDD) lors de la Réunion Annuelle du Collège Américain de Neuropsychopharmacologie. Les données des Études 501 et 502 ont montré des améliorations significatives des taux de rémission et de réponse, ainsi que des symptômes d'anxiété, avec CAPLYTA par rapport au placebo. Plus précisément, l'Étude 501 a montré un taux de réponse de 45,6 % contre 24,0 % pour le placebo, et un taux de rémission de 25,9 % contre 13,6 % pour le placebo. L'Étude 502 a rapporté un taux de réponse de 40,1 % contre 25,3 % pour le placebo, et un taux de rémission de 25,0 % contre 13,5 % pour le placebo. De plus, une analyse post-hoc de l'Étude 403 a indiqué que CAPLYTA avait considérablement amélioré les symptômes d'anhedonie chez les patients atteints de MDD et de dépression bipolaire avec caractéristiques mixtes.
Les données de sécurité regroupées des Études 501 et 502 ont confirmé un profil de sécurité favorable, avec des réactions indésirables courantes comprenant des vertiges, une sécheresse buccale, de la somnolence, des nausées et de la fatigue. CAPLYTA a également montré un faible risque de symptômes extrapyramidaux et moteurs.
Intra-Cellular Therapies hat Daten aus seinem Phase-3-Programm für CAPLYTA (Lumateperon) als ergänzende Therapie für die Major Depressive Disorder (MDD) auf dem Jahresmeeting des American College of Neuropsychopharmacology präsentiert. Die Daten aus den Studien 501 und 502 zeigten signifikante Verbesserungen in den Remissions- und Antwortquoten sowie in den Angstsymptomen im Vergleich zu Placebo. Insbesondere zeigte Studie 501 eine Antwortquote von 45,6% gegenüber 24,0% für Placebo und eine Remissionsrate von 25,9% gegenüber 13,6% für Placebo. Studie 502 berichtete von einer Antwortquote von 40,1% gegenüber 25,3% für Placebo und einer Remissionsrate von 25,0% gegenüber 13,5% für Placebo. Darüber hinaus deutete eine nachträgliche Analyse aus Studie 403 darauf hin, dass CAPLYTA die Anhedonie-Symptome bei Patienten mit MDD und bipolarer Depression mit gemischten Merkmalen signifikant verbessert hat.
Die zusammengefassten Sicherheitsdaten aus den Studien 501 und 502 bestätigten ein günstiges Sicherheitsprofil, wobei häufige Nebenwirkungen Schwindel, Mundtrockenheit, Schläfrigkeit, Übelkeit und Müdigkeit umfassten. CAPLYTA zeigte außerdem ein niedriges Risiko für extrapyramidale und motorische Symptome.
- Significant improvement in remission and response rates for CAPLYTA in Studies 501 and 502.
- Robust improvement in anxiety symptoms as measured by the GAD-7 scale.
- Favorable safety and tolerability profile in pooled data from Studies 501 and 502.
- Significant improvement in anhedonia symptoms in Study 403.
- Common adverse reactions include dizziness, dry mouth, somnolence, nausea, and fatigue.
Insights
Presentations complement topline data with new data from two pivotal studies (Studies 501 and 502) evaluating lumateperone as an adjunctive therapy for the treatment of major depressive disorder
Data shows robust remission and response efficacy rates in patients taking CAPLYTA
Robust improvements in anxiety symptoms were also observed in patients taking CAPLYTA as measured by the Generalized Anxiety Disorder Questionnaire (GAD-7)
Pooled safety and tolerability data from Studies 501 and 502 show favorable safety and tolerability profile for CAPLYTA consistent with prior studies
A post-hoc analysis from Study 403 in mixed features shows CAPLYTA significantly improved anhedonia symptoms as measured by the MADRS anhedonia factor score
BEDMINSTER, N.J., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, today announced presentations at the 63rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP) which included new efficacy, safety, and tolerability analyses from its CAPLYTA adjunctive major depressive disorder (MDD) pivotal program.
“We have previously shared positive results from Studies 501 and 502 demonstrating a robust clinical profile of CAPLYTA as an adjunctive treatment in MDD with strong efficacy results in the Montgomery Asberg Depression Rating Scale (MADRS) total score, the Clinical Global Impression Scale for Severity of Illness (CGI-S) and the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR-16) scale. We are excited to share new data that further characterize CAPLYTA’s robust efficacy and favorable safety and tolerability profile,” said Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies. “In addition, the improvements in anhedonia symptoms observed in Study 403 further contribute to enriching CAPLYTA’s profile in the treatment of MDD and bipolar depression.”
Details of the presentations are as follows:
Poster T126 “Lumateperone as Adjunctive Therapy in Patients with Major Depressive Disorder: Results from a Randomized, Double-blind, Phase 3 Trial,” Tuesday, December 10
Poster W85 “Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From an Additional Randomized, Double-Blind, Phase 3 Trial,” Wednesday, December 11
These poster presentations highlight the efficacy of lumateperone 42mg adjunctive to anti-depressant therapy (ADT) shown in two similarly designed trials (Studies 501 and 502). In these studies, lumateperone 42 mg demonstrated significant and clinically meaningful efficacy over placebo, improving depressive symptoms and disease severity. Lumateperone plus ADT improved depression as measured by both clinician-rated and patient-reported outcomes (MADRS total score, CGI-S score, and QIDS-SR-16 total score). Subject to FDA approval, we believe these results demonstrate lumateperone represents a promising new treatment option for adults with MDD with inadequate response to prior ADT.
In both studies, MADRS response and remission rates were significantly greater with lumateperone compared to placebo. Specifically, in Study 501 the response rates for CAPLYTA were
In Study 501 anxiety symptoms were measured using the GAD-7 scale. Lumateperone plus ADT significantly improved self-reported anxiety symptoms, as measured by the GAD-7 total score, compared with placebo from baseline to Day 43 (Cohen’s d effect size (ES): 0.43; p<0.0001).
Poster W84 “Safety and Tolerability of Lumateperone 42 mg for the Treatment of Major Depressive Disorder: A Pooled Analysis of 2 Randomized Placebo-Controlled Trials,” Wednesday, December 11
A pooled analysis of Studies 501 and 502 demonstrates the safety and tolerability of lumateperone 42 mg plus ADT in patients with MDD who had inadequate response to ADT.
The most common adverse reactions in the lumateperone group (defined as ≥
In Studies 501 and 502 changes in cardiometabolic parameters, prolactin levels and body morphology with lumateperone were similar to placebo. The risk of extrapyramidal symptoms and motor symptoms with lumateperone was low.
Poster W88 “Lumateperone Treatment for Major Depressive Episodes With Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder: A Post Hoc Analysis of Anhedonia,” Wednesday, December 11
The poster reports on a post-hoc analysis from Study 403 evaluating the efficacy of lumateperone 42mg monotherapy in improving the anhedonia factor score in patients with MDD or bipolar depression with mixed features. The results from this analysis support lumateperone to treat the broad range of anhedonia symptoms of a major depressive episode in these patient populations.
Anhedonia, which is diminished interest or pleasure, occurs in approximately
Lumateperone significantly improved the MADRS anhedonia factor score from baseline to Day 43 compared with placebo in the combined MDD/bipolar depression population with mixed features (least squares mean difference (LSMD)= -3.4; ES= 0.63; p<0.0001) as well as both individual populations of patients with MDD with mixed features (LSMD= -3.4; ES= 0.63; p<0.0001) and bipolar depression with mixed features (LSMD= -3.3; ES= 0.61; p<0.0001).
CAPLYTA® (lumateperone) is indicated in adults for the treatment of schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.
Important Safety Information
Boxed Warnings:
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.
- Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.
Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.
Warnings & Precautions: Antipsychotic drugs have been reported to cause:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.
- Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.
- Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.
- Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.
- Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.
- Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.
- Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.
- Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
- Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.
- Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.
- Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.
Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors.
Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Dose reduction is recommended for patients with moderate or severe hepatic impairment.
Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.
CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules.
Please click here to see full Prescribing Information including Boxed Warning.
About CAPLYTA (lumateperone)
CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.
Lumateperone is being studied for the treatment of major depressive disorder, and other psychiatric and neurological disorders. Lumateperone is not FDA-approved for these disorders.
About Intra-Cellular Therapies
Intra-Cellular Therapies is a biopharmaceutical company founded on Nobel prize-winning research that allows us to understand how therapies affect the inner-workings of cells in the body. The company leverages this intracellular approach to develop innovative treatments for people living with complex psychiatric and neurologic diseases. For more information, please visit www.intracellulartherapies.com.
Forward-Looking Statements
This news release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the potential approval of CAPLYTA (lumateperone) for the treatment of major depressive disorder as adjunctive therapy; our expectations regarding the commercialization of CAPLYTA; our plans to conduct clinical or non-clinical trials and the timing of developments with respect to those trials, including enrollment, initiation or completion of clinical conduct, or the availability or reporting of results; plans to make regulatory submissions to the FDA and the timing of such submissions and any product approvals; whether clinical trial results will be predictive of future real-world results; whether CAPLYTA will serve an unmet need; the goals of our development programs; our beliefs about the potential utility of our product candidates; and development efforts and plans under the caption “About Intra-Cellular Therapies.” All such forward-looking statements are based on management's present expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, the following: there are no guarantees that CAPLYTA will be commercially successful; we may encounter issues, delays or other challenges in commercializing CAPLYTA; whether CAPLYTA receives adequate reimbursement from third-party payors; the degree to which CAPLYTA receives acceptance from patients and physicians for its approved indications; challenges associated with execution of our sales activities, which in each case could limit the potential of our product; results achieved in CAPLYTA in the treatment of schizophrenia and bipolar depression following commercial launch of the product may be different than observed in clinical trials, and may vary among patients; challenges associated with supply and manufacturing activities, which in each case could limit our sales and the availability of our product; risks associated with our current and planned clinical trials; we may encounter unexpected safety or tolerability issues with CAPLYTA following commercial launch for the treatment of schizophrenia or bipolar depression or in ongoing or future trials and other development activities; there is no guarantee that a generic equivalent of CAPLYTA will not be approved and enter the market before the expiration of our patents; there is no guarantee that our supplemental New Drug Application (sNDA) for the treatment of MDD will be approved, if at all, on the timeline that we expect; our other product candidates may not be successful or may take longer and be more costly than anticipated; product candidates that appeared promising in earlier research and clinical trials may not demonstrate safety and/or efficacy in larger-scale or later clinical trials or in clinical trials for other indications; our proposals with respect to the regulatory path for our product candidates may not be acceptable to the FDA; our reliance on collaborative partners and other third parties for development of our product candidates; impacts on our business, including on the commercialization of CAPLYTA and our clinical trials, as a result of the COVID-19 pandemic, the conflicts in Ukraine, Russia and the Middle East, global economic uncertainty, inflation, higher interest rates or market disruptions; and the other risk factors detailed in our public filings with the Securities and Exchange Commission. All statements contained in this press release are made only as of the date of this press release, and we do not intend to update this information unless required by law.
Contact:
Intra-Cellular Therapies, Inc.
Juan Sanchez, M.D.
Vice President, Corporate Communications and Investor Relations
646-440-9333
Burns McClellan, Inc.
Cameron Radinovic
cradinovic@burnsmc.com
646-930-4406
FAQ
What are the remission rates for CAPLYTA in Study 501?
How does CAPLYTA perform in terms of response rates in Study 502?
What anxiety improvements were observed with CAPLYTA in Study 501?
What were the common adverse reactions to CAPLYTA in the pooled analysis?
What is the significance of the post-hoc analysis from Study 403?
What are the safety findings from the pooled analysis of Studies 501 and 502?
