Thanatophoric Dysplasia, Type I

SAN DIEGO, June 2, 2023 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today presented findings from a meta-analysis of three long-term studies evaluating INGREZZA® (valbenazine) capsules that demonstrated substantial and sustained improvements in tardive dyskinesia (TD) in adults with or without concomitant antipsychotic therapy. The data (Poster #4) were presented at 2023 Psych Congress Elevate in Las Vegas. The analysis of the three studies (KINECT™ 3, KINECT™ 4, and J-KINECT™) demonstrated that treatment with once-daily INGREZZA (40 mg or 80 mg) resulted in substantial and sustained TD improvement through week 48 as measured by the Abnormal Involuntary Movement Scale (AIMS) total score, with no meaningful differences between study completers taking antipsychotics at baseline (AP+) and those who were not (AP-). Upon withdrawal of INGREZZA, both subgroups experienced a return toward baseline severity of TD symptoms, demonstrating the potentially persistent nature of TD, even in patients no longer taking antipsychotic therapy. Researchers concluded that continuous treatment with INGREZZA to manage TD may be warranted irrespective if they were on concurrent antipsychotic therapy. "TD may persist even after patients are no longer taking antipsychotic therapy," said Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "These data from three long-term studies reinforce the continuing value of INGREZZA in TD management, regardless of antipsychotic status." Key results from the meta-analysis demonstrated the following: Mean baseline AIMS scores within each study ranged from 7.9 to 14.9 in the subgroup taking antipsychotics at baseline (AP+) and from 10.9 to 14.5 in the subgroup not taking antipsychotics at baseline (AP-) Mean changes from baseline in AIMS total scores within the combined group were similar between the AP+ and AP- subgroups and indicated substantial TD improvements with INGREZZA 40 mg and 80 mg at week 48 (AP+, -6.1; AP-, -6.5) Both AP+ and AP- subgroups within the combined group experienced a return toward baseline severity at week 52, four weeks after INGREZZA 40 mg or 80 mg withdrawal (AP+, -2.1; AP-, -1.4) Additional presentations include: Global Improvements and Psychiatric Stability in Adults With Tardive Dyskinesia and Mood Disorder: Post Hoc Analyses of Two Long-Term Valbenazine Studies (Poster #3) The full abstracts presented by Neurocrine Biosciences at 2023 Psych Congress Elevate are available on the meeting website and can be accessed by registering. About the KINECT™ 3 Phase 3 Study KINECT 3 is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study, in which 234 participants with moderate to severe TD and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder) received six weeks of once-daily INGREZZA (40 mg or 80 mg capsules) or placebo (participants randomized to 80 mg started on 40 mg for one week). Subsequent to the completion of the six-week placebo-controlled dosing, participants receiving INGREZZA continued on their current dose, and placebo participants were randomized to receive either once-daily 40 mg or once-daily 80 mg of INGREZZA, through week 48 (42-week blinded treatment extension period; placebo participants randomized to 80 mg started on 40 mg for one week), followed by a four-week drug-free washout. Dose reduction to 40 mg was allowed for participants who were unable to tolerate the 80 mg dose. Patients were discontinued if the new dose was not tolerated. The study met its primary endpoint of change-from-baseline in AIMS at week six in the 80 mg once-daily dosing group compared to placebo, as assessed by expert central blinded video raters. The mean change from baseline to week six in the AIMS rating was -3.2 for the 80 mg once-daily group as compared to -0.1 in the placebo group (P>0.0001). Sustained TD improvements were seen with INGREZZA 40 mg and 80 mg through week 48. INGREZZA was generally well tolerated throughout 48 weeks of treatment. The most common adverse reactions (≥ five percent and twice the rate of placebo) during the six-week, double-blind, placebo-controlled phase was somnolence with the frequency of adverse events being similar among all treatment groups. Treatment-emergent adverse events (TEAEs) were consistent with those of prior studies. There were no drug-drug interactions identified in participants who were utilizing a wide range of psychotropic and other concomitant medications, and participants generally remained psychiatrically stable throughout the study. About the KINECT™ 4 Phase 3 Study KINECT 4 is a Phase 3, open-label study, in which 163 participants with moderate to severe TD and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder) received 48 weeks of open-label treatment with once-daily INGREZZA (40 mg or 80 mg capsules) followed by a four-week washout. Dosing was initiated at 40 mg/day in all participants, with escalation to 80 mg/day at week 4 based on effectiveness and tolerability. Dose reduction to 40 mg was allowed in participants who could not tolerate the 80 mg dose. Patients were discontinued if the new dose was not tolerated. Participants experienced TD improvements during long-term treatment, as demonstrated by mean change from baseline to week 48 in AIMS total score (sum of items 1-7, evaluated by site raters) with INGREZZA 40 mg/day (-10.2) or 80 mg/day (-11.0). Consistent with previous studies, INGREZZA was generally well tolerated. After week four, TEAEs that occurred in ≥5 percent of all participants (combined dose groups) were urinary tract infection (8.5 percent) and headache (5.2 percent). Changes from baseline in psychiatric stability, vital signs, electrocardiogram parameters and laboratory test values were generally small and not clinically significant. About J-KINECT™ Phase 2 and 3 Studies In 2015, Mitsubishi Tanabe Pharma Corporation (MTPC) exclusively licensed the development and commercialization rights for valbenazine in Japan and certain other Asian countries with Neurocrine Biosciences. MTPC conducted J-KINECT, the Phase 2/3, multicenter, randomized, double-blind, placebo-controlled study to confirm the efficacy and safety of valbenazine 40 mg or 80 mg administered once daily for up to 48 weeks in adult patients with moderate or severe tardive dyskinesia (TD). The study showed a significant improvement in the primary efficacy endpoint of the mean change from baseline in the Abnormal Involuntary Movement Rating Scale (AIMS) total score at week 6 of treatment with valbenazine compared to placebo. The persistence of efficacy was also shown in the AIMS total score at week 48. In addition, valbenazine was also well tolerated. The incidence of adverse events was highest in the 80 mg group and included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia and tremor. In 2021, MTPC received approval of valbenazine capsules 40mg for the treatment of TD in Singapore, Thailand, South Korea, and Indonesia, followed by approval in Japan and Malaysia in 2022. About Tardive Dyskinesia (TD) Tardive dyskinesia (TD) is a movement disorder that is characterized by uncontrollable, abnormal, and repetitive movements of the face, torso and/or other body parts, which may be disruptive and negatively impact patients. The condition is associated with taking certain kinds of mental health medicines (like antipsychotics) that help control dopamine receptors in the brain. Taking antipsychotics commonly prescribed to treat mental illnesses such as major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder, and other prescription medicines (metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD. In patients with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement. The symptoms of TD can be severe and are often persistent and irreversible. TD is estimated to affect approximately 600,000 people in the U.S. About INGREZZA® (valbenazine) Capsules INGREZZA, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is an FDA-approved product indicated for the treatment of adults with tardive dyskinesia, a condition associated with uncontrollable, abnormal, and repetitive movements of the face, torso, and/or other body parts. INGREZZA is thought to work by reducing the amount of dopamine released in a region of the brain that controls movement and motor function, helping to regulate nerve signaling in adults with tardive dyskinesia. VMAT2 is a protein in the brain that packages neurotransmitters, such as dopamine, for transport and release in presynaptic neurons. INGREZZA, developed by Neurocrine Biosciences, is novel in that it selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic, or muscarinic receptors. 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. Important Information Approved Use INGREZZA® (valbenazine) capsules is a prescription medicine used to treat adults with movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia). It is not known if INGREZZA is safe and effective in children. IMPORTANT SAFETY INFORMATION Do not take INGREZZA if you: are allergic to valbenazine, or any of the ingredients in INGREZZA. INGREZZA may cause serious side effects, including: Sleepiness (somnolence). Do not drive, operate heavy machinery, or do other dangerous activities until you know how INGREZZA affects you. Heart rhythm problems (QT prolongation). INGREZZA may cause a heart problem known as QT prolongation. Symptoms of QT prolongation may include: fast, slow, or irregular heartbeat shortness of breath dizziness or fainting Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you faint. Abnormal movements (Parkinson-like). Symptoms include: shaking, body stiffness, trouble moving or walking, or keeping your balance. Before taking INGREZZA, 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. The most common side effect of INGREZZA is sleepiness (somnolence). Other side effects include changes in balance (balance problems, dizziness) or an increased risk of falls, headache, feelings of restlessness, dry mouth, constipation, and blurred vision. These are not all of the possible side effects of INGREZZA. 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 or call 1-800-FDA-1088. Please see accompanying INGREZZA full Product Information. About Neurocrine Biosciences 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, Parkinson'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, Twitter and Facebook. (*in collaboration with AbbVie) NEUROCRINE, the Neurocrine logo, 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 and the value INGREZZA may bring to patients. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: risks and uncertainties associated with the commercialization of INGREZZA; risks that clinical trial activities may not be predictive of real-world results or of results in subsequent clinical trials; risks that INGREZZA may be precluded from commercialization by the proprietary rights of third parties, or have unintended side effects or adverse reactions; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA; risks associated with our dependence on third parties for development and manufacturing activities related to INGREZZA and our product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that our products, and/or our product candidates 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 associated with potential generic entrants for our products; 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 March 31, 2023. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof. ©2023 Neurocrine Biosciences, Inc. All Rights Reserved. SOURCE Neurocrine Biosciences, Inc.

START study provides real-world data for AUSTEDO with the use of a 4-week patient titration kit for adults with tardive dyskinesia (TD), including utilization and patient satisfaction AUSTEDO is the only vesicular monoamine transporter 2 (VMAT2) inhibitor with 3-year long-term data1,2 approved for adults with TD and chorea associated with Huntington’s disease (HD) Additional presentations include long-term safety, and tolerability of UZEDY™ (risperidone), which was approved by the FDA on April 28, 2023 for the treatment of schizophrenia in adults as a subcutaneous injection once monthly or once every two months using a pre-filled syringe TEL AVIV, Israel & PARSIPPANY, N.J.--(BUSINESS WIRE)-- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced 12 presentations across its neuroscience portfolio featured at the Psych Congress Elevate 2023 Annual Meeting taking place on June 1-4, 2023. Two presentations feature real-world data for AUSTEDO (deutetrabenazine) tablets for adults living with TD. Data presented will include interim findings from the START trial, a Phase 4 study investigating real-world utilization of AUSTEDO with a 4-week patient titration kit along with treatment success as measured at the end of treatment. The kit was developed to help patients with TD and HD chorea achieve appropriate dosage and follow dosing schedule during the titration period, guiding patients through the first four weeks of titration from a starting dose of 12 mg/day to 30 mg/day by week four. “These interim Phase 4 data results demonstrate promising real-world patient satisfaction with AUSTEDO and the 4-week patient titration kit for adults living with TD, which mirror outcomes to those seen in clinical trials,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “These results further support the potential to help patients with TD find their appropriate dose, remain on-schedule and achieve real-world outcomes similar to those seen in the pivotal studies.” Interim START trial results from the first 50 patients enrolled in the TD cohort show that 78% of patients successfully completed the 4-week patient titration kit, and the mean dose at week 12 was 32.8 mg/day. Nearly half of all patients achieved treatment success as assessed by both the Clinical Global Impression of Change (CGIC; 49%) and Patient Global Impression of Change (PGIC; 47%) at the end of treatment (week 12). Additionally, a majority of patients found it easy to understand when and which dosage to take (72%), easy to remember to take their medication (77%), easy to change the dose weekly (74%), and easy to use the kit overall (77%), demonstrating the titration kit helped with daily use and following the recommended dose schedule. “TD is a chronic movement disorder that affects up to one in four people who take certain medications for mental health issues.3-5 Changing or stopping their mental health medications can risk destabilizing their underlying condition, so managing their TD can become a tremendous burden, often resulting in difficulty adhering to their medications,” said Andrew Cutler, MD, Associate Clinical Professor of Psychiatry, SUNY Upstate Medical University and Chief Medical Officer, Neuroscience Education Institute. “Patients using the 4-week patient titration kit were able to successfully reach a dose of 24 mg/day and higher, while maintaining adherence with treatment, demonstrating that having an effective treatment option with an easy-to-use titration kit can help patients with daily use and following the recommended dosing schedule to better manage their TD symptoms and stay on track with their mental health treatment plans.” In addition to twice-daily AUSTEDO, patients and healthcare providers now have the additional option of a once-daily formulation, AUSTEDO® XR (deutetrabenazine), which was recently approved by the FDA in February 2023 and is available to patients in the U.S. More information about the new formulation and 4-week Sample Titration Kit can be found here. Teva will also present findings from studies evaluating potential drug-drug interactions with VMAT2 inhibitors, as well as patient and healthcare provider perspectives on the impact of TD. Results from clinical studies evaluating UZEDY and TV-44749 in schizophrenia, and the DECIDE survey will be presented at the meeting as well. The full set of data sponsored by Teva includes: Exhibit Hall & Poster Presentations: Friday, June 2 and Saturday, June 3, 10:30 AM - 11:15 AM PT AUSTEDO: (De novo) Real-World Effectiveness of Deutetrabenazine When Initiated Using a 4-Week Patient Titration Kit: Interim Results of the START Study (Poster #30) (De novo) Patient Satisfaction With the Deutetrabenazine 4-week Patient Titration Kit: Interim Results of the START Study (Poster #21) (De novo) Drug-Drug Interactions With Vesicular Monoamine Transporter 2 Inhibitors: Population Estimate of Patients With Tardive Dyskinesia at Risk in Real-World Clinical Practice (Poster #20) (De novo) Patients With Tardive Dyskinesia at Risk for Drug-Drug Interactions With Vesicular Monoamine Transporter 2 Inhibitors Across Age Groups, Underlying Psychiatric Conditions, and Payer Types (Poster #22) TD: (Encore) Differences in Patient and Healthcare Professional Perspectives on the Key Impacts of Tardive Dyskinesia (Poster #28) UZEDY: (De novo) TV-46000–a Long-Acting Subcutaneous Antipsychotic (LASCA) for the Treatment of Schizophrenia: Local Tolerability and Injection Site Reactions (Poster #17) (Encore) Long-term Safety, Tolerability, and Effectiveness of TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), in Patients With Schizophrenia: A Phase 3, Randomized, Double-Blind Study (SHINE) (Poster #15) TV-44749: (De novo) The SOLARIS Protocol: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial Assessing Safety and Efficacy of TV-44749 for Subcutaneous Administration (Olanzapine for Extended-Release Injectable Suspension Use) in Adults With Schizophrenia (Poster #16) Schizophrenia: (De novo) Impact of Clinician and Patient Characteristics on Use of and Attitudes Toward Long-Acting Injectable Antipsychotics in Schizophrenia: A Survey of US Psychiatric Clinicians (DECIDE) (Poster #5) (De novo) Transitioning Patients to Long-Acting Injectable Antipsychotics: Attitudes and Perceptions of US Clinicians Based on a Hypothetical Case (Results from the DECIDE Survey) (Poster #7) (De novo) Preferences for Selecting and Initiating Long-Acting Injectable Antipsychotics: A Survey of US Psychiatric Clinicians (Poster #6) About Tardive Dyskinesia (TD) Tardive dyskinesia (TD) is a highly debilitating, chronic movement disorder that affects one in four people who take certain mental health treatments and is characterized by uncontrollable, abnormal, and repetitive movements of the face, torso, and/or other body parts, which may be disruptive and negatively impact individuals.3-5 About Schizophrenia Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts.6 Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability.6-8 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.7,8 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.6 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.6 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.9-11 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.6-11 About AUSTEDO XR Extended-Release Tablets and AUSTEDO Tablets AUSTEDO and AUSTEDO XR are the first and only vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease. Safety and effectiveness in pediatric patients have not been established. AUSTEDO XR is the once-daily formulation of AUSTEDO. INDICATIONS AND USAGE AUSTEDO® XR (deutetrabenazine) extended-release tablets and AUSTEDO® (deutetrabenazine) tablets are indicated in adults for the treatment of chorea associated with Huntington’s disease and for the treatment of tardive dyskinesia. IMPORTANT SAFETY INFORMATION Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression. Contraindications: AUSTEDO XR and AUSTEDO are contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO XR and AUSTEDO are also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine or valbenazine. Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO XR or AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects. QTc Prolongation: AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range. AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems. Akathisia, Agitation, and Restlessness: AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy. Parkinsonism: AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy. Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO XR and AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO XR or AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence. Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO XR and AUSTEDO. Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects. Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntington’s disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia. Adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets. Please see accompanying full Prescribing Information, including Boxed Warning. About UZEDY UZEDY (risperidone) extended-release injectable suspension, for subcutaneous use, is indicated for the treatment of schizophrenia in adults. In clinical trials, UZEDY reduced the risk of relapse by up to 80%.12 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.12 For full prescribing information, visit . INDICATION AND USAGE UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults. IMPORTANT SAFETY INFORMATION WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly 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. 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 . 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 Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and innovative medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of innovative and biopharmaceutical products. Learn more at . Cautionary Note Regarding Forward-Looking Statements This 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 the development and commercial success of AUSTEDO (deutetrabenazine) tablets and AUSTEDO XR (deutetrabenazine) extended-release tablets as well as UZEDY; our ability to successfully compete in the marketplace, including our ability to develop and commercialize biopharmaceutical products, competition for our innovative medicines, our ability to achieve expected results from investments in our product pipeline, our ability to develop and commercialize additional pharmaceutical products, and the effectiveness of our patents and other measures to protect our intellectual property rights; our substantial indebtedness; our business and operations in general, including, the impact of global economic conditions and other macroeconomic developments and the governmental and societal responses thereto, and costs and delays resulting from the extensive pharmaceutical regulation to which we are subject; compliance, regulatory and litigation matters, including failure to comply with complex legal and regulatory environments; other financial and economic risks; and other factors discussed in our Quarterly Report on Form 10-Q for the first quarter of 2023 and in our Annual Report on Form 10-K for the year ended December 31, 2022, 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. Hauser, R. A., Barkay, H., Fernandez, H. H. et al. Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia is Associated with Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study. Frontiers in Neurology (2022). . 2. Frank, S., Testa, C., Edmondson, M.C. et al. The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study. CNS Drugs (2022). . 3. Warikoo N, Schwartz T, Citrome L. Tardive dyskinesia. In: Schwartz TL, Megna J, Topel ME, eds. Antipsychotic Drugs. Hauppauge, NY: Nova Science Publishers. 2013:235-258. 4. Waln O, Jankovic J. An Update on Tardive Dyskinesia: From Phenomenology to Treatment. Tremor Other Hyperkinet Mov. 2013;3:1-11. 5. Tardive dyskinesia. National Alliance on Mental Illness website. . Accessed May 4, 2023. 6. Substance Abuse and Mental Health Services Administration. Schizophrenia. April 24, 2023. . Accessed May 2023. 7. Velligan DI, Rao S. The epidemiology and global burden of schizophrenia. J Clin Psychiatry. 2023;84(1):MS21078COM5. . 8. 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. 9. Emsley, R., & Kilian, S. (2018). Efficacy and safety pro paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review. Neuropsychiatric disease and treatment, 14, 205–223. 10. Emsley, R., Chiliza, B., Asmal, L. et al. (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13, 50. 11. 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. 12. UZEDY™ (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc.

WEDNESDAY, May 31, 2023 -- A joint attention-based deep learning system provides good predictive performance for differentiating autism spectrum disorder (ASD) from typical development (TD), according to a study published online May 25 in JAMA Network Open . Chanyoung Ko, M.D., from the Yonsei University College of Medicine in Seoul, South Korea, and colleagues trained deep learning models to distinguish ASD from TD and to differentiate ASD symptom severities. Joint attention tasks were administered to children with and without ASD, and video data were obtained from multiple institutions. Ninety-five of 110 children completed study measures. The analytical population included 45 children with ASD and 50 with TD. The researchers observed good predictive performance for the deep learning ASD versus TD model for initiation of joint attention (IJA; area under the receiver operating characteristic curve [AUROC], 99.6 percent; accuracy, 97.6 percent; precision, 95.5 percent; and recall, 99.2 percent); low-level response to joint attention (RJA; AUROC, 99.8 percent; accuracy, 98.8 percent; precision, 98.9 percent; and recall, 99.1 percent); and high-level RJA (AUROC, 99.5 percent; accuracy, 98.4 percent; precision, 98.8 percent; and recall, 98.6 percent). Reasonable predictive performance was seen for IJA, low-level RJA, and high-level RJA in the deep learning-based ASD symptom severity models. "We believe our research opens possibilities for gathering large data sets on behavioral biomarkers through standardized video data acquisition setup amenable to computer vision and deep learning and applicable to a wide range of neuropsychiatric conditions," the authors write. Two authors disclosed ties to LumanLab, and three disclosed having patents for the method and apparatus for diagnosis of developmental disability severity in toddlers based on joint attention. Abstract/Full Text Posted May 2023