D2 receptor

NG101 Significantly Reduced Incidence of Nausea by 40% and Frequency of Vomiting by 56% without Changing the Safety Profile of the GLP-1 AgonistWOBURN, Mass., Oct. 16, 2024 (GLOBE NEWSWIRE) -- Neurogastrx, Inc. today announced positive topline results from a new study of NG101 (metopimazine mesylate) showing significant reduction of nausea and vomiting side effects caused by a glucagon-like peptide 1 (GLP-1) agonist medication. NG101 is an oral, peripherally restricted dopamine D2 receptor antagonist. “The randomized, double-blind, placebo-controlled proof-of-concept (POC) safety and efficacy study showed positive effects of NG101 in participants who received double the starting dose of the GLP-1 agonist semaglutide,” said Cyril De Colle, Ph.D., Chief Scientific Officer, Neurogastrx. “Findings from this study suggest NG101 could be an important addition to GLP-1 agonist therapy, helping more patients adhere to treatment as they transition to the higher doses needed to reach weight loss and broader health goals.” Key efficacy endpoints showed NG101 significantly: Reduced the incidence of nausea by 40% (p=0.0343)Reduced the frequency of vomiting by 56% (p=0.0412) NG101 also significantly reduced both the duration of nausea (p=0.0101) and the participant-reported severity of nausea (p=0.0225). The addition of NG101 to semaglutide dosing was not associated with any new safety findings, including the incidence of other common adverse events (AEs) such as diarrhea or constipation. There were no serious AEs and no discontinuations due to treatment emergent adverse events (TEAEs) in the study. Gastrointestinal (GI) adverse events, especially nausea and vomiting, are the primary challenge to titration and adherence of GLP-1 therapy. A recent real-world adherence study utilizing an IQVIA database followed over 160,000 new semaglutide weight loss patients and showed a 50% discontinuation rate at six months and 70% at one year. “Our POC study offers hope to patients who cannot tolerate these medicines long enough to realize their benefits,” said James O’Mara, President and Chief Executive Officer, Neurogastrx. “We look forward to discussions with the FDA to initiate a larger Phase 2/3 study in 2025, with the goal to bring this product to patients.” Study Design A total of 90 participants aged 18-55 received a single subcutaneous dose of semaglutide (0.5 mg) along with five days of NG101 20 mg twice per day (BID) or placebo. The study evaluated the efficacy of NG101 in reducing the incidence, duration and severity of nausea and vomiting. Efficacy endpoints included: Number of days with TEAEs of nausea and/or vomiting within four days (96 hours) following a single subcutaneous GLP-1 agonist injection.Moderate and/or severe TEAEs of nausea and/or vomiting within four days (96 hours) following a single subcutaneous GLP-1 agonist injection (as graded by the principal investigator or designee).TEAEs of nausea and/or vomiting within four days (96 hours) following a single subcutaneous GLP-1 agonist injection. The study also evaluated the safety of NG101 (20 mg BID) in participants receiving a single subcutaneous injection of the GLP-1 agonist. Primary safety endpoints included incidence and severity of TEAEs (other than nausea and vomiting), and standard laboratory assessments. For more details, go to www.clinicaltrials.gov, NCT006500429. About Neurogastrx, Inc. Neurogastrx, Inc. is a privately held specialty pharmaceutical company developing transformative therapies to advance the treatment of GI disorders for which meaningful therapeutic innovation is required to satisfy unmet patient need and disease burden. Media ContactAmanda BreedingScient PRamanda@scientpr.com

Oral and poster presentations of results from Study 501 evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) Poster presentations of post-hoc analyses from Study 403 including the prespecified patient population with MDD or bipolar depression with mixed features who also had anxious distress NEW YORK, Sept. 23, 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 of lumateperone including the results from Phase 3 adjunctive Major Depressive Disorder (MDD), Study 501 at the 37th European College of Neuropsychopharmacology (ECNP) Congress being held September 21 - 24, 2024 in Milan, Italy. “We are very pleased to present additional lumateperone data across depressive disorders including remarkable positive results from Study 501 evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD at ECNP. The robust efficacy demonstrated by lumateperone, coupled with its favorable safety and tolerability profile, position CAPLYTA to become an important medicine for the treatment of MDD,” said Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies. “We are on track to submit our lumateperone sNDA for the adjunctive treatment of MDD including the results of Studies 501 and 502 later this year.” Details of the presentations are as follows: Study 501 Presentations Oral presentation: “Adjunctive Lumateperone Significantly Improves Symptoms of Major Depressive Disorder: Topline Results From a Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial.” Monday, September 23, 15:00 - 16:20 CEST. P2127: “Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder: Results From a Randomised, Double-blind, Phase 3 Trial.” Monday, September 23 12:35 - 14:00 CEST. Study 403 Presentations P2113: “Lumateperone in the Treatment of Patients With Major Depressive Disorder and Bipolar Disorder With Anxious Distress and Mixed Features.” Monday, September 23 12:35 - 14:00 CEST. P2096: “Lumateperone in the Treatment of Major Depressive Disorder and Bipolar Depression With Mixed Features: Efficacy Across Symptoms.” Monday, September 23 12:35 - 14:00 CEST. In Study 501, lumateperone met the primary endpoint of change from baseline at Week 6 on the Montgomery Asberg Depression Rating Scale (MADRS) total score versus placebo with a 4.9-point reduction (p<0.0001; Cohen’s d effect size (ES)= 0.61). Statistically significant reductions in depressive symptoms as measured by the MADRS were seen at the earliest time point tested, Week 1, and these improvements continued throughout the course of the trial. Lumateperone also met the key secondary endpoint of change from baseline on the clinician-rated Clinical Global Impression Scale for Severity of Illness (CGI-S) (p < 0.0001; ES: 0.67). On a patient-reported measure, the Quick Inventory of Depressive Symptomatology Self Report scale (QIDS), patients reported robust reduction in their depressive symptoms (p <0.0001). Adverse events were similar to those seen in prior studies of lumateperone as a treatment for bipolar depression and schizophrenia. Mean changes in key metabolic parameters including glucose, insulin, triglycerides, and total, LDL and HDL cholesterol were similar between lumateperone and placebo. Importantly, mean changes in weight were also similar to placebo. In an additional, similarly-designed trial, Study 502, lumateperone 42 mg plus an antidepressant met primary and key secondary efficacy endpoints (MADRS Total Score [LSMD vs placebo=−4.5; ES= 0.56; P<0.0001] and CGI-S score [LSMD vs placebo=−0.5; ES= 0.51; P<0.0001]) and was generally safe and well tolerated in patients with MDD with inadequate antidepressant response. Details of Study 502 will be presented at upcoming conferences. Study 403 presentations highlight important analyses of lumateperone’s double-blind placebo-controlled study in patients with either MDD or bipolar depression exhibiting mixed features. Poster #2113 presents a post-hoc analysis of Study 403 evaluating lumateperone’s efficacy in the prespecified patient population with MDD or bipolar depression with mixed features who also met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for anxious distress. In this analysis, lumateperone significantly improved depression symptoms and severity (MADRS Total score and CGI-S score) compared with placebo. Lumateperone also significantly improved MADRS inner tension single-item score in patients with co-morbid anxious distress. Both anxious distress and mixed features are specified in the DSM-5 and are common in patients with major depressive episodes associated with MDD and bipolar disorder. Patients with these specifiers have more severe symptoms, more comorbidities, increased suicide risk, and/or poorer treatment response than patients without these specifiers. Poster #2096 presents a post-hoc analysis of Study 403 individual MADRS items. Treatment with lumateperone significantly improved a broad range of depression symptoms across individual MADRS items. About Major Depressive Disorder Major Depressive Disorder (MDD) is a common mood disorder in the U.S. affecting an estimated 21 million adults each year. Depressive disorders are the number two cause of years lived with disability in the world. Symptoms include sadness, hopelessness, helplessness, feelings of guilt, irritability, loss of interest in formerly pleasurable activities, cognitive impairment, disturbed sleep patterns, and suicide ideation or behavior. MDD can cause severe functional impairment, adversely affecting interpersonal relationships, and may impact quality of life. Approximately two-thirds of patients with depression fail to achieve remission with first-line treatment. 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, 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; 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 planned sNDA for the treatment of MDD will be submitted or 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 Relations646-440-9333 Burns McClellan, Inc.Cameron Radinoviccradinovic@burnsmc.com646-930-4406

As a leader in neuroscience, Teva remains committed to helping address unmet needs in the treatment of schizophrenia through scientific and clinical advances that support optimal treatment options and decisions for patients and HCPsNew data demonstrate switching to UZEDY at four weeks after the last dose of once-monthly RBP-7000 provided the most comparable pharmacokinetic (PK) profile based on relevant simulations, with comparable doses identifiedNew ADVANCE survey findings highlight key patient-reported reasons for accepting long-acting injectable treatment options, including improvement of symptoms/condition, recommendation by a HCP, and ease of use data TEL AVIV, Israel and PARSIPPANY, N.J., Sept. 21, 2024 (GLOBE NEWSWIRE) -- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today presented data informing clinical strategies for switching patients to UZEDY®, an extended-release injectable suspension of risperidone for subcutaneous use every one or two months for the treatment of schizophrenia in adults, from a once-monthly subcutaneous injection of Perseris® (RBP-7000). The results were presented during the 37th Annual European College of Neuropsychopharmacology (ECNP) Congress taking place between September 21-24, 2024, in Milan, Italy. Schizophrenia is a complex medical condition that may require switching from an oral option or between different long-acting injectable options during the patient treatment journey. These data further clinical understanding of optimal treatment strategies when switching to UZEDY from Perseris®. “Schizophrenia patients and healthcare providers rely on evidence-based studies that can help inform their treatment decisions. That is why Teva is dedicated to building on our commitment to neuroscience and schizophrenia and helps provide these clinical insights on UZEDY switching strategies, along with its role in long-acting treatment options,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Up to 80% of schizophrenia patients experience multiple relapses in the first five years, making switching treatments a common experience in the search for optimal treatment. With UZEDY, Teva is building a robust portfolio of research that can help determine if and when it may be the right long-acting option.” In a population pharmacokinetic (PopPK) analysis, simulations were conducted to predict pharmacokinetic (PK) exposures when switching to UZEDY 4-6 weeks after the last injection of once-monthly RBP-7000. The simulation models indicated that switching to UZEDY 4 weeks after the last dose of once-monthly RBP-7000 resulted in comparable PK properties of UZEDY at both the initial exposure and steady state. Comparable doses included UZEDY at 100 mg (once-monthly dosing) or 200 mg (once-every-two-months dosing) to 120 mg of once-monthly RBP-7000.1 Any switching strategy should be determined by clinicians on an individual patient basis, considering factors such as patient preference, scheduling convenience and potential tolerability issues or risk of symptom breakthrough. “Every person living with schizophrenia has unique treatment needs and preferences that may also evolve over time. For my patients, I encourage discussion around key factors like treatment adherence, dosing frequency, symptom control, and rate of relapse which inform what treatment option may be the most appropriate,” said Christoph Correll, MD, Professor of Psychiatry at the Zucker School of Medicine, Hempstead, NY. “For healthcare providers, there is also a significant knowledge gap in the available clinical data on switching patients between the various LAI treatment options, which have differing pharmacokinetic properties and dosing considerations. Insights from studies like these are crucial for researchers and clinicians like myself, as they help us become more informed and better serve our patients.” Additional key data being presented at ECNP 2024 included new quantitative results from the ADVANCE (Attitudes Driving Regional Differences in LAI Antipsychotic Utilization for Schizophrenia Among HCPs, Patients and Caregivers) surveys, including: Among 447 people living with schizophrenia and 375 caregivers, most common patient-reported reasons for accepting an LAI (n=331) were improvement of symptoms/condition with LAIs (68%, n=224), recommendation by their HCP (65%, n=214) and ease of using LAIs versus oral antipsychotics (57%, n=189).1Patients also reported using LAIs due to fewer side effects versus oral antipsychotics (38%, n=127) and to help prevent hospitalization (20%, n=67).1Caregivers (n=229) reported that patients accepted LAIs based on ease of use versus oral antipsychotics (78%, n=178), to help prevent hospitalization (62%, n=143) and perception that LAIs would work better for improving condition/symptoms (62%, n=143).1Among a sample of 791 HCPs from 8 different countries, most HCPs reported that the primary reason for recommending an LAI to a patient was nonadherence to oral medication, with the exception of South Korea where the most common reason was that an LAI would be more efficacious than oral.1The primary reasons cited for not recommending an LAI were patient clinical characteristics and the lack of an available LAI formulation of the patient’s current oral treatment, except for China and South Korea, where the primary reasons were LAI cost to patient and LAI product not marketed, respectively.1 About SchizophreniaSchizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts.2 Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability.2,3,4 Approximately 1% of the world’s population will develop schizophrenia in their lifetime, and 3.5 million people in the U.S. are currently diagnosed with the condition.3,4 Although schizophrenia can occur at any age, the average age of onset tends to be in the late teens to the early 20s for men, and the late 20s to early 30s for women. 4 The long-term course of schizophrenia is marked by episodes of partial or full remission broken by relapses that often occur in the context of psychiatric emergency and require hospitalization.4 Approximately 80% of patients experience multiple relapses over the first five years of treatment, and each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology.5,6,7 Patients are often unaware of their illness and its consequences, contributing to treatment nonadherence, high discontinuation rates, and ultimately, significant direct and indirect healthcare costs from subsequent relapses and hospitalizations.2,3,4,5,6,7 About UZEDYUZEDY (risperidone) extended-release injectable suspension, for subcutaneous use, is indicated for the treatment of schizophrenia in adults. In clinical trials, UZEDY significantly reduced the risk of schizophrenia relapse.1,8 UZEDY administers risperidone through copolymer technology under license from MedinCell that allows for absorption and sustained release after subcutaneous injection. UZEDY is the only long-acting, subcutaneous formulation of risperidone available in both one- and two-month dosing intervals.8 For full prescribing information, visit https://www.uzedy.com/globalassets/uzedy/prescribing-information.pdf. INDICATION AND USAGE UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSISElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population. See below for additional Important Safety Information. IMPORTANT SAFETY INFORMATION CONTINUED CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone. WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring. Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown. The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment. Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone. Dyslipidemia has been observed in patients treated with atypical antipsychotics. Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended. Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents. Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication. Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. Leukopenia, Neutropenia and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC (< 1000/mm3) and follow their WBC until recovery. Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely. Seizures: During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration. Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention. Body temperature regulation. Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions. ADVERSE REACTIONS The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis and pharyngolaryngeal pain. The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule. DRUG INTERACTIONS Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone.Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration.Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.UZEDY may antagonize the pharmacologic effects of dopamine agonists.Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS) USE IN SPECIFIC POPULATIONS Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinicaland-research-programs/pregnancyregistry/. Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness and EPS. Fertility: UZEDY may cause a reversible reduction in fertility in females. Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients. Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY. Patients with Parkinson’s disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS. Please see the full Prescribing Information for UZEDY, including Boxed WARNING. About TevaTeva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a global pharmaceutical leader with a category-defying portfolio, harnessing our generics expertise and stepping up innovation to continue the momentum behind the discovery, delivery and expanded development of modern medicine. For over 120 years, Teva’s commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its 37,000 employees across 58 markets to push the boundaries of scientific innovation and deliver quality medicines to help improve health outcomes of millions of patients every day. To learn more about how Teva is all in for better health, visit www.tevapharm.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize UZEDY (risperidone) extended-release injectable suspension for the treatment schizophrenia; our ability to successfully compete in the marketplace, including our ability to develop and commercialize additional pharmaceutical products; our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development; and other factors discussed in our Quarterly Report on Form 10-Q for the second quarter of 2024 and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the section captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. ________________________ 1 Data on file. Parsippany, NJ: Teva Neuroscience, Inc.2 Substance Abuse and Mental Health Services Administration. Schizophrenia. https://www.samhsa.gov/mental-health/schizophrenia. Accessed November 2023.3 Velligan DI, Rao S. The epidemiology and global burden of schizophrenia. J Clin Psychiatry. 2023;84(1):MS21078COM5. https://doi-org.libproxy1.nus.edu.sg/10.4088/JCP.MS21078COM5 4 Wander C. (2020). Schizophrenia: opportunities to improve outcomes and reduce economic burden through managed care. The American journal of managed care, 26(3 Suppl), S62–S68. https://doi-org.libproxy1.nus.edu.sg/10.37765/ajmc.2020.43013 5 Emsley, R., & Kilian, S. (2018). Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review. Neuropsychiatric disease and treatment, 14, 205–223. 6 Emsley, R., Chiliza, B., Asmal, L. et al. (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13, 50. 7 Andreasen, N. C., et al. (2013). Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. The American journal of psychiatry, 170(6), 609–615.8 UZEDY™ (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc. IR Contacts Ran Meir+1 (267) 468-4475 Yael Ashman+972 (3) 914 8262 Sanjeev Sharma+1 (973) 658 2700 PR Contacts Kelley DoughertyEden Klein+1 (973) 832-2810+972 (3) 906 2645