Esophageal Motility Disorders

PK modeling data provide insights into potential dosing conversions and strategies for switching to UZEDY from a long-acting injectable (LAI) formulation of risperidone microspheres (R064766) Additional UZEDY data include a new analysis from the Phase 3 RISE trial reinforcing its efficacy and safety profile in adults with schizophrenia ADVANCE, a global survey study, will also provide real-world findings on LAI utilization from healthcare professionals, caregivers and patients 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 the presentation of eight studies from its LAI schizophrenia research program, including data evaluating UZEDY, an extended-release injectable suspension of risperidone for subcutaneous use every one or two months for the treatment of schizophrenia in adults. The data were presented at the 2024 Congress of the Schizophrenia International Research Society (SIRS) taking place from April 3-7, 2024 in Florence, Italy. “As part of Teva’s commitment to advancing treatment innovation for schizophrenia patients, this research provides clinical insights into how healthcare providers may switch appropriate patients to UZEDY, a subcutaneous risperidone LAI option with flexible dosing,” said Eric Hughes, MD, Ph.D, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Schizophrenia is a complex mental health condition where the treatment needs and preferences of those living with it may evolve over time. These data collectively demonstrate the efficacy and safety profile of UZEDY – reinforcing its potential as a treatment option that may help lower rates of relapse and hospitalization.” Presented data include population pharmacokinetic (PopPK) modeling to investigate dosing conversion strategies for switching patients to a once-monthly or once every two-months subcutaneous dose of UZEDY from a biweekly intramuscular LAI formulation of risperidone microspheres (R064766). The analysis aims to address the knowledge gap as limited clinical data currently exist on optimal strategies for switching between the various available LAI treatment options, which have differing pharmacokinetic (PK) properties. In the PopPK analysis, patient model simulations showed that switching to UZEDY at 4-6 weeks after the last dose of R064766 provided comparable PK exposures by the second dose. Specifically, switching patients to UZEDY 5 weeks after the last dose of R064766 achieved PK exposures similar to those achieved with R064766 at a steady state. The optimal switching strategy should be determined by clinicians on an individual basis, considering factors such as patient preference, scheduling convenience, and potential tolerability issues or risk of symptom breakthrough. Additional key data being presented at the SIRS Annual Meeting include: New data from RISE (Risperidone Subcutaneous Extended-Release Study), the Phase 3 pivotal trial that supported the FDA approval of UZEDY. An analysis estimated the number needed to treat (NNT) and the number needed to harm (NNH), clinically relevant measures that help provide healthcare providers with an understanding of the benefits and risks of UZEDY and inform clinical decision-making. Qualitative data from two ADVANCE (Attitudes Driving Regional Differences in LAI Antipsychotic Utilization for Schizophrenia Among Healthcare Professionals, Patients, and Caregivers) surveys: In the healthcare provider survey, ten psychiatrists (spending an average of 45% of their time at hospital-based outpatient clinics) and seven psychiatric nurses (averaging 47% of time at community mental health centers) were interviewed. Findings suggest that regional differences in LAI utilization rates are likely influenced by a combination of factors, including systemic, HCP, and patient factors. In the patient survey, approximately 20 patients and 19 caregivers completed a 60-minute interview regarding the use of LAIs in schizophrenia. Unfavorable early experiences, especially in the inpatient setting, can negatively impact patients’ perception of and willingness to accept LAIs. The survey findings offer further key insights into addressing global adherence and inconsistent utilization challenges with LAIs. Below is the full set of data presented by Teva at SIRS 2024. AUSTEDO ® XR (deutetrabenazine): (Encore) Occupational Impact of Tardive Dyskinesia (TD): a Cross-Sectional, International Survey Assessing the Perceptions and Experiences of Patients With TD and Physicians Who Treat TD (Encore) Burden and Management of Tardive Dyskinesia (TD): A Cross-Sectional, International Survey Study to Assess the Perceptions and Experiences of Physicians and Patients With TD (De novo) Patient and Caregiver Experiences With Tardive Dyskinesia: Emotions, Challenges, and Unmet Needs in the Patient Journey UZEDY (risperidone): (De novo) Switching Patients With Schizophrenia to TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), From Risperidone Microspheres (R064766): An Exploration of Population Pharmacokinetic (PopPK)–Based Strategies (De novo) Clinical Benefit and Risk Profile of TV-46000 for Patients With Schizophrenia as Assessed by Number Needed to Treat (NNT) and Number Needed to Harm (NNH) TV-44749 (olanzapine): (De novo) TV-44749, a Long-Acting Subcutaneous (sc) Injectable Formulation of Olanzapine is Designed to Provide Sustained Controlled Concentrations and to Eliminate the Causes of Post-Injection delirium/sedation Syndrome (PDSS) (De novo) Population Pharmacokinetic Modeling Following Administration of Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use to Support Dose Selection for Phase 3 Clinical Trial (SOLARIS) LAI Real-World Insights: (De novo) Attitudes DriVing regional differences in LAI ANtipsychotic utilization for schizophrenia among healthcare professionals, patients, and CaregivErs (ADVANCE): healthcare professional qualitative interviews (De novo) Attitudes DriVing regional differences in LAI ANtipsychotic utilization for schizophrenia among healthcare professionals, patients, and CaregivErs (ADVANCE): patient and caregiver qualitative interviews (De novo) Initiation Regimens for Long-Acting Injectable Antipsychotics Requiring Oral Supplementation: Impact on Subsequent Maintenance Treatment Adherence and Persistence 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 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. See below for additional Important Safety Information. TV-44749 (olanzapine) is an investigational extended-release injectable suspension for subcutaneous use and is not approved by any regulatory authority for any use and its safety and efficacy are not established. About Schizophrenia Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts. 1 Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability. 1,2,3 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. 2,3 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. 3 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. 3 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. 4,5,6 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. 1,2,3,4,5,6 About UZEDY UZEDY (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. 7,8 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. 7 For full prescribing information, visit https://www.uzedy.com/globalassets/uzedy/prescribing-information.pdf . 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 D 2 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/mm 3 ) 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 AUSTEDO ® XR Extended-Release Tablets and AUSTEDO ® Tablets AUSTEDO XR and AUSTEDO are the first vesicular monoamine transporter 2 (VMAT2) inhibitors 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 Teva Teva 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 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: our ability to successfully develop and commercialize UZEDY; our ability to successfully develop and commercialize AUSTEDO XR; our ability to develop and obtain regulatory approvals to our late-stage pipeline assets, including olanzapine LAI (TEV-‘749); 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 this press release, and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the sections 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 Substance Abuse and Mental Health Services Administration. Schizophrenia. https://www.samhsa.gov/mental-health/schizophrenia . Accessed November 2023. 2 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 . 3 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 4 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. 5 Emsley, R., Chiliza, B., Asmal, L. et al. (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13, 50. 6 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. 7 UZEDY™ (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc. 8 Data on file. Parsippany, NJ: Teva Neuroscience, Inc. View source version on businesswire.com : https://www.businesswire.com/news/home/20240406098130/en/ IR Ran Meir +1 (267) 468-4475 Yael Ashman +972 (3) 914 8262 Sanjeev Sharma +1 (973) 658 2700 PR Kelley Dougherty +1 (973) 832-2810 Eden Klein +972 (3) 906 2645 Source: Teva Pharmaceutical Industries Limited

FLORHAM PARK, N.J., April 03, 2024 (GLOBE NEWSWIRE) -- Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, announced today that members of the management team will participate in a fireside chat at the 23rd Annual Needham Virtual Healthcare Conference on Wednesday, April 10, 2024, at 9:30 a.m. ET. Company management will also participate in one-on-one meetings during the conference, which will run from April 8-11, 2024. To access the live webcast and an archived recording of the event, visit the News & Events section of the Phathom website at . Recordings will be available for 90 days following the conclusion of the meeting. About Phathom Pharmaceuticals, Inc. Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases. Phathom has in-licensed the exclusive rights to vonoprazan, a first-in-class potassium-competitive acid blocker (PCAB) that is currently marketed in the United States as VOQUEZNA® (vonoprazan) tablets for the treatment of Erosive GERD and relief of related heartburn in adults, in addition to VOQUEZNA® TRIPLE PAK® (vonoprazan tablets, amoxicillin capsules, clarithromycin tablets) and VOQUEZNA® DUAL PAK® (vonoprazan tablets, amoxicillin capsules) for the treatment of H. pylori infection in adults. For more information about Phathom, visit the company’s website at and follow on LinkedIn and X. MEDIA CONTACT Nick Benedetto 1-877-742-8466 media@phathompharma.com INVESTOR CONTACT Eric Sciorilli 1-877-742-8466 ir@phathompharma.com © 2024 Phathom Pharmaceuticals. All rights reserved.

Fanapt® Treatment is Now Available to Adult Patients for the Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder Approval Represents Significant Novel Indication for Vanda's Fanapt® Franchise WASHINGTON, April 2, 2024 /PRNewswire/ -- Vanda Pharmaceuticals, Inc. (Vanda) (Nasdaq: VNDA) today announced that the U.S. Food and Drug Administration (FDA) has approved Fanapt® (iloperidone) tablets for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. Fanapt® is an atypical antipsychotic agent that has been used for the acute treatment of patients with schizophrenia since its FDA approval in 2009. "Manic or mixed episodes associated with bipolar I disorder are highly complex conditions, which require a host of trusted options to meet individual patient needs. With over 100,000 patient years of experience, Fanapt is a familiar therapeutic agent that offers flexible dosing with a well-known safety profile. This FDA approval gives patients and service providers a new treatment option for managing bipolar I disorder," said Mihael H. Polymeropoulos M.D., Vanda's President, CEO and Chairman of the Board. Bipolar disorder is a serious, highly prevalent psychiatric chronic condition affecting approximately 2.8% of the U.S. adult population, with 83% of them classified as severe1. Bipolar disorder is a group of disorders that are characterized by periods of elevated mood alternating with periods of depressed mood. For the diagnosis of bipolar I disorder, people must have experienced one or more episodes of mania and most would have episodes of both mania and depression. Patients with bipolar I disorder with manic or mixed episodes are a subset of those approximately 10 million Americans with bipolar disorder1. The marketing approval of Fanapt® in bipolar I disorder with manic and mixed episodes significantly increases the commercial opportunity for Fanapt®. Stephen Stahl, MD, PhD, Professor of Psychiatry at the University of California San Diego, said, "Many patients today are still unable to find suitable treatment options for effectively managing bipolar disorder. Tailoring the right treatment for the right patient is critical for effective care, and the approval of Fanapt represents an important milestone. Fanapt possesses a well-studied safety profile, and its approval will provide patients with a new and effective option for treating a highly complex disorder." The approval of Fanapt® for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder was based on a pivotal study randomizing approximately 400 patients. The primary endpoint measured in Week 4 of treatment was assessed by the Young Mania Rating Scale (YMRS), a rating scale of clinical severity in the core symptoms of mania. At the end of the study (Week 4), Fanapt® treated patients showed a larger improvement than placebo treated patients, and this difference was highly statistically significant (p=0.000008). YMRS was assessed at the end of Weeks 1, 2, 3 and 4. Statistically significant benefit in the Fanapt® treated group over placebo was observed as early as the Week 2 assessment. The safety pro Fanapt® in this study was similar to that seen in Fanapt® studies previously conducted for the treatment of schizophrenia in adults. Dr. Polymeropoulos continued, "Today's announcement marks a significant step forward for one of Vanda's leading franchises and underscores the effectiveness of our strategy in pursuing innovative therapies that address high unmet medical needs to improve the lives of patients. With this as our foundation, we have established a resilient business, with a diverse product pipeline, a history of revenue growth and strong financial position. We remain focused on providing critical medicines to patients across the world while creating sustainable, long-term value." References: Harvard Medical School, 2007. National Comorbidity Survey (NSC). (2017, August 21). Retrieved from About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on X @vandapharma. About Fanapt® For full U.S. Prescribing Information for Fanapt®, including indication, Boxed Warnings and Important Safety Information, visit our Web site at . INDICATION AND IMPORTANT SAFETY INFORMATION Fanapt® (iloperidone) is indicated for the treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. Titrate the dosage of Fanapt® to avoid orthostatic hypotension. BOXED 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. Fanapt® is not approved for use in patients with dementia-related psychosis. CONTRAINDICATIONS Known hypersensitivity to Fanapt® or to any components in the formulation. Anaphylaxis, angioedema, and other hypersensitivity reactions have been reported. WARNING AND PRECAUTIONS In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. See boxed warning. QT prolongation: Fanapt® prolongs QT interval and may be associated with arrhythmia and sudden death. Avoid use of Fanapt® in combination with other drugs that are known to prolong QTc; use caution and consider dose modification when prescribing Fanapt® with other drugs that inhibit Fanapt® metabolism. Monitor serum potassium and magnesium in patients at risk for electrolyte disturbances. Neuroleptic malignant syndrome, a potentially fatal symptom, has been reported in association with antipsychotic drugs including Fanapt®. Manage with immediate discontinuation of drug, treatment if needed, and close monitoring. Tardive dyskinesia: The risk of tardive dyskinesia may increase as the duration of treatment and total cumulative dose increases. Discontinue Fanapt® if clinically appropriate. Metabolic changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, 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. Weight gain has been reported. Monitor glucose, lipids, and weight when starting Fanapt® and thereafter. Seizures: Use Fanapt® cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Orthostatic hypotension: Dizziness, tachycardia, and syncope can occur with standing. More rapid titration would be expected to increase the rate of orthostatic hypotension and syncope. Fanapt® may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments initially and recurrently during therapy. Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Fanapt® at the first sign of a decline in WBC in the absence of other causative factors. Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, Fanapt® elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating compounds. Body temperature regulation: Appropriate care is advised when prescribing Fanapt® for patients who will be experiencing conditions which may contribute to an elevation in core body temperature. Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Fanapt® should be used cautiously in patients at risk for aspiration pneumonia, including the elderly and those with advanced Alzheimer's dementia. Priapism: Cases have been reported in association with Fanapt® treatment. Potential for cognitive and motor impairment: Use caution when operating machinery. Intraoperative floppy iris syndrome (IFIS): IFIS has been observed in some patients treated with alpha-1 adrenergic blockers. Instruct patients to tell their ophthalmologist about their use of Fanapt® before cataract or glaucoma surgery. ADVERSE REACTIONS Commonly observed adverse reactions (incidence ≥5% and 2-fold greater than placebo) were: Schizophrenia: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased. Bipolar mania: tachycardia, dizziness, dry mouth, hepatic enzymes increased, nasal congestion, weight increased, hypotension, and somnolence. DRUG INTERACTIONS The dose of Fanapt® should be reduced by one-half in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor. USE IN SPECIFIC POPULATIONS Fanapt® may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates with third trimester exposure. Nursing mothers are advised not to breastfeed while taking Fanapt®. The safety and effectiveness of Fanapt® has not been established in children and adolescents. Fanapt® is not recommended for patients with severe hepatic impairment. The dose of Fanapt® should be reduced by one-half in patients who are poor metabolizers of CYP2D6. Please see full Prescribing Information, including BOXED WARNING. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this release, including, but not limited to statements regarding Vanda's ability to make Fanapt® available to patients with manic or mixed episodes associated with bipolar I disorder and the commercial opportunity for Fanapt®, are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, market acceptance of Fanapt® as an acute treatment for adults with manic or mixed episodes associated with bipolar I disorder, Vanda's dependence on third-party manufacturers to manufacture Fanapt® in sufficient quantities and quality, and the effectiveness of Vanda's sales and marketing infrastructure. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 pr@vandapharma.com Jim Golden / Jack Kelleher / Dan Moore Collected Strategies VANDA-CS@collectedstrategies.com Company Codes: NASDAQ-NMS:VNDA