Teva to Present Data for AUSTEDO® XR (deutetrabenazine) Extended-Release Tablets, AUSTEDO® (deutetrabenazine) Tablets and UZEDY™ (risperidone) Extended-Release Injectable Suspension at Psych Congress 2023

• Teva will share 16 data presentations across its neuroscience portfolio including AUSTEDO, once-daily AUSTEDO XR, UZEDY, TV-44749 (olanzapine) and AJOVY^® (fremanezumab) injection
• Presentation highlights include data for AUSTEDO in the tardive dyskinesia (TD) START study on real-world effectiveness and adherence when initiating treatment with a 4-Week Patient Titration Kit and safety data for UZEDY along with results from the RISE (The Risperidone Subcutaneous Extended-Release Study) and SHINE (A Study to Test TV-46000 for Maintenance Treatment of Schizophrenia) studies
• Onsite activities will include a symposium on the DECIDE (Determining Clinician Factors for Implementing LAIs and Defeating Barriers) study, which surveyed clinician perspectives on the use of long-acting injectable (LAI) antipsychotics

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 16 data presentations across its neuroscience portfolio happening at Psych Congress on September 6-10 in Nashville, TN. Abstracts include data for AUSTEDO, once-daily AUSTEDO XR, UZEDY, TV-44749 and AJOVY. Once-daily AUSTEDO XR, a new formulation of twice-daily AUSTEDO was approved by the U.S. Food and Drug administration (FDA) in February 2023 for adults with TD and chorea associated with Huntington’s disease (HD), and UZEDY, a long-acting formulation of risperidone for subcutaneous use, was approved by the FDA in April 2023 for adults with schizophrenia.^1,2 TV-44749 is an investigational formulation of olanzapine currently being studied in adults with schizophrenia.³

“Because of the immense impact that mental health and neurological conditions like schizophrenia, TD and HD pose for patients, we are constantly striving to advance research that can enhance available treatment options,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Following this year’s FDA approval of once-daily AUSTEDO XR and UZEDY and the excitement they have received from the medical community, we are thrilled to continue to share research showcasing their potential for patients living with these debilitating conditions.”

In addition to these data presentations, Teva will also be hosting a symposium to discuss results of the DECIDE study, highlighting perspectives from U.S. psychiatric clinicians on selecting and initiating LAI antipsychotics as well as the real-world barriers that cause LAIs to remain underutilized in clinical practice.

The full set of data presented by Teva includes:

Symposium: Saturday, September 9 from 2:00 PM – 3:00 PM CT

• Determining Clinician Factors for Implementing LAIs and Defeating Barriers (DECIDE Survey Results)

Poster Presentations: Friday, September 8 from 1:30 PM – 3:00 PM CT and Saturday, September 9 from 1:30 PM – 3:00 PM CT

Once-daily AUSTEDO XR/AUSTEDO and Tardive Dyskinesia (TD):

• (De Novo) Dosing and Treatment Patterns of Deutetrabenazine When Initiated Using a 4-Week Patient Titration Kit: Interim Results of the START Study (Poster #89)
• (Encore) Real-World Effectiveness of Deutetrabenazine When Initiated Using a 4-Week Patient Titration Kit: Interim Results of the START Study (Poster #90)
• (Encore) Drug–Drug Interactions With Vesicular Monoamine Transporter 2 Inhibitors: Population Estimate of Patients With Tardive Dyskinesia at Risk in Real-World Clinical Practice (Poster #139)
• (Encore) Real-World Antipsychotic and Vesicular Monoamine Transporter Type 2 Inhibitor Treatment Patterns in Patients Newly Diagnosed With Tardive Dyskinesia (Poster #140)
• (Encore) Real-World Antipsychotic Treatment Modification With and Without Deutetrabenazine in Patients Newly Diagnosed With Tardive Dyskinesia (Poster #141)
• (Encore) Exposure-Response Analysis to Compare Changes in the Clinical Endpoints for Tardive Dyskinesia and Chorea in Huntington Disease Following Once-Daily and Twice-Daily Tablet Formulations of Deutetrabenazine (Poster #155)

UZEDY and Schizophrenia:

• (De Novo) Behavioral-, Neurologic-, Metabolic-, Endocrine-, and Cardiovascular-Related Adverse Events and Assessments in Patients With Schizophrenia Treated With TV-46000 (Poster #100)
• (De Novo) Impact of Treatment With TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), at Different Stages of Schizophrenia: a Post Hoc Analysis (Poster #101)
• (De novo) Introducing S.C.O.P.E.™ Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement—An Interactive Digital Platform to Educate on Schizophrenia Care (Poster #102)
• (Encore) Long-term Safety, Tolerability, and Effectiveness of TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), in Patients With Schizophrenia (SHINE) (Poster #103)
• (Encore) TV-46000—a Long-Acting Subcutaneous Antipsychotic (LASCA) for the Treatment of Schizophrenia: Local Tolerability and Injection Site Reactions (Poster #105)
• (Encore) Preferences for Selecting and Initiating Long-Acting Injectable Antipsychotics: A Survey of US Psychiatric Clinicians (Results from the DECIDE Survey) (Poster #109)
• (Encore) Transitioning Patients to Long-Acting Injectable Antipsychotics: Attitudes and Perceptions of US Clinicians Based on a Hypothetical Case (Results From the DECIDE Survey) (Poster #110)

TV-44749:

• (Encore) SOLARIS Protocol: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of TV-44749 for Subcutaneous Use (Olanzapine for Extended-Release Injectable Suspension Use) in Adults With Schizophrenia (Poster #104)

AJOVY:

• (Encore) Impact of Fremanezumab Treatment on Disability Outcomes in Patients with Migraine and Major Depressive Disorder: Results of the UNITE Study (Poster #134)
• (Encore) Efficacy of Fremanezumab in Reducing Depression in Patients with Migraine and Major Depressive Disorder: Results of the UNITE Study (Poster #130)

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.^4-6

About Schizophrenia
Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts.⁷ Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability.^7-9 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.^8,9 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.⁷ 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.⁷ 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.^10-12 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.^7-12

About AUSTEDO XR Extended-Release Tablets and AUSTEDO Tablets
AUSTEDO and AUSTEDO XR 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 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%.² 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.² 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.

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.

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