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Teva Announces Post Hoc Analysis of Long-Term Data Examining Treatment with AUSTEDO® (deutetrabenazine) Tablets in Adult Patients with Tardive Dyskinesia

TEL AVIV, Israel & PARSIPPANY, N.J.–()–Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced results from a post hoc analysis of a long-term, 3-year open-label extension (OLE) study examining efficacy and safety endpoints for the use of AUSTEDO (deutetrabenazine) tablets in younger (<55 years) and older (≥55 years) patients with tardive dyskinesia (TD). The findings, published online in The American Journal of Geriatric Psychiatry, evaluated the long-term use of AUSTEDO with the total motor Abnormal Involuntary Movements Scale (AIMS) score, and measures of treatment success and quality of life.

TD affects about 500,000 people in the United States and approximately 25 percent of the global population taking first-and second-generation antipsychotics.1,2 It is usually a result of prolonged use of treatments that block dopamine receptors in the brain, such as antipsychotics commonly prescribed to treat mental illnesses like schizophrenia, bipolar disorder and depression, as well as certain anti-nausea medications. Notably, TD incidence rates are estimated to be three to five times higher in patients over 50 years old.3

“This analysis helps further our understanding of AUSTEDO as a treatment that may help alleviate uncontrolled movements in adults but is particularly compelling when considering treatment of older patients,” said Martha Sajatovic, MD, University Hospitals Cleveland Medical Center at Case Western Reserve University School of Medicine in Ohio. “Symptoms of TD can worsen in severity over time, especially in patients 55 years and older who have had long-term treatment with an antipsychotic prescription. As this occurs, they may experience balance and coordination issues, putting them at an increased risk for falls that may be especially concerning.”

This post hoc analysis was conducted to potentially inform treatment decisions in younger and older patients with TD treated with deutetrabenazine. Data were derived from the single-arm 3-year OLE study in patients that had successfully completed either the Phase 3 ARM-TD or AIM-TD study (n=337). The safety profile of AUSTEDO was generally similar across both the younger and older patients. Due to the uncontrolled nature of the data and post hoc analysis, no determination of statistical significance can be made.

About AUSTEDO (deutetrabenazine) Tablets

AUSTEDO is the first and only vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of tardive dyskinesia in adults and for the treatment of chorea associated with Huntington’s disease. 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 individuals. Safety and effectiveness in pediatric patients have not been established.

Indications and Usage

AUSTEDO® (deutetrabenazine) tablets is indicated in adults for the treatment of chorea associated with Huntington’s disease and for the treatment of tardive dyskinesia in adults.

IMPORTANT SAFETY INFORMATION

Depression and Suicidality in Patients with Huntington’s Disease: 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 is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO is contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO is 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 (Xenazine®) or valbenazine (Ingrezza®).

Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.

QTc Prolongation: AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO is administered within the recommended dosage range. 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; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: 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 dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: 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 dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of 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 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.

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.

Please see accompanying full Prescribing Information, 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 specialty 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 specialty and biopharmaceutical products. Learn more at 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 the commercial success of AUSTEDO; our ability to successfully compete in the marketplace, including our ability to develop and commercialize biopharmaceutical products, competition for our specialty products, including AUSTEDO, AJOVY® and COPAXONE®; 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 uncertainty regarding the COVID-19 pandemic and its impact on our business, financial condition, operations, cash flows, and liquidity and on the economy in general, our ability to successfully execute and maintain the activities and efforts related to the measures we have taken or may take in response to the COVID-19 pandemic and associated costs therewith, costs and delays resulting from the extensive pharmaceutical regulation to which we are subject or delays in governmental processing time due to travel and work restrictions caused by the COVID-19 pandemic; 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 Annual Report on Form 10-K for the year ended December 31, 2020, 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.

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1 Tardive Dyskinesia Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Tardive-Dyskinesia-Information-Page. Accessed August 12, 2021

2 Carbon, M, Hsieh, C-H, Kane, JM, et al. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. Journal of Clinical Psychiatry. 2017;78(3): e264–78.

3 Woerner MG, Alvir JMaJ, Saltz BL, et al., Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry. 1998; 155: 1521–1528.

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