Findings evaluate safety, quality of life and patient-centered outcome measures up to 145 weeks

Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced new data from the 3-year open-label extension study of AUSTEDO^® (deutetrabenazine) Tablets that studied patients with tardive dyskinesia (TD) will be presented at the 2021 American Psychiatric Association (APA) Virtual Annual Meeting, being held online from May 1-3.

The new data includes three abstracts that examine the long-term safety, quality of life (QoL) and patient-centered outcome measures of patients living with TD who were treated with AUSTEDO up to 145 weeks following two pivotal 12-week studies (ARM-TD and AIM-TD).

“TD is a serious movement disorder and we continue to evaluate AUSTEDO to determine its therapeutic potential following the pivotal clinical trials,” said Denisa Hurtukova, MD, VP, Head of North America Medical Affairs. “The data being presented at APA give healthcare providers valuable insights into safety and certain aspects of quality of life among TD patients, which could have an important impact on treatment considerations and ultimately the wellbeing of patients.”

In an analysis of the long-term safety of AUSTEDO, 337 patients with 723 patient-years of exposure were evaluated, all of whom had completed ARM-TD or AIM-TD. AUSTEDO was administered using a response-driven dosing regimen, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. Safety measures included incidence of any adverse events (AEs), serious adverse events (SAEs) and AEs leading to withdrawal, dose reduction or dose suspension, as well as the most common AEs (≥4 percent). Since differences in incidence rates may be related to different durations of observation, exposure-adjusted incidence rates (EAIRs) were used to calculate AE frequencies. 269 (79.8 percent) patients reported ≥1 AE and AEs considered by the investigator to be treatment related were reported in 154 (45.7 percent) patients. Low EAIRs were reported for most AEs, including 1.22 for any AE, 0.09 for SAEs, 0.34 for treatment-related AEs, 0.06 for AEs leading to withdrawal, 0.05 for AEs leading to dose suspension, and 0.09 for AEs leading to dose reduction. The most common AEs (EAIRs) were anxiety (0.06), depression (0.05), somnolence (0.05), weight decreased (0.05) and urinary tract infection (0.05).

• Poster 4807: Long-Term Safety of Deutetrabenazine in Patients with Tardive Dyskinesia: Results from the Completed, 3-year Open-Label Extension Study

The OLE also investigated AUSTEDO in relation to patients’ QoL using the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) score, a disease-specific QoL questionnaire adjusted to focus on the impact of TD. Patients’ QoL was evaluated based on the mean change +/- SE from baseline in the mCDQ-24 total score and the stigma, pain, activities of daily living (ADL), emotional and social subdomain scores through week 106. Of the 337 analyzed, changes in mean mCDQ-24 total scores from baseline were observed at week 6 (-3.2 +/- 0.68) and sustained through week 106 (-5.2 +/- 1.11). Treatment resulted in clinically meaningful improvements based on changes as measured by the mCDQ-24 total score and the stigma, pain, ADL, emotional and social subdomain scores.

• Poster 4849: Long-Term Deutetrabenazine Treatment is Associated with Sustained Improvements in Quality of Life in Patients with Tardive Dyskinesia

Finally, the OLE also evaluated patient-centric outcomes, including the percentage of patients to achieve treatment success (defined as “much improved” or “very improved”) on the Patient Global Impression of Change (PGIC), change from baseline in the patient-reported modified mCDQ-24 score and changes from baseline in the Abnormal Involuntary Movement Scale (AIMS) items 8, 9, 10, which are clinician-rated global judgments of the overall severity of abnormal movements, the incapacitation due to abnormal movements, and the patient’s awareness of abnormal movements, respectively. The analysis found more than half of the patients achieved PGIC treatment success at week 6, and the proportion increased over time from 54 percent at weeks 6 and 15, to 61 percent at week 54, 64 percent at week 106 and 63 percent at week 145. According to the mCDQ-24 score, patients demonstrated improvement in QoL at week 6 (mean change +/- SE from baseline: -3.2 +/- 0.68) that continued throughout the study (week 15, -5.0 +/- 0.70; week 54, -5.0 +/- 0.89; week 106, -5.2 +/- 1.11). Patients also experienced improvements from baseline in AIMS items 8, 9 and 10, which were sustained through week 145 (mean change +/- SE: -1.3 +/- 0.07 for item 8; -1.3 +/- 0.08 for item 9, and -1.3 +/- 0.09 for item 10).

• Poster 4390: Improvements in Patient-Centered Outcome Measures with Long-Term Deutetrabenazine Treatment Among Patients with Tardive Dyskinesia

Posters are available online and can be accessed via the APA meeting website at: www.psychiatry.org/annualmeeting.

AUSTEDO^® Indications and Usage

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

Important Safety Information About AUSTEDO^®

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 regarding AUSTEDO, 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. 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: that we are substantially dependent on our generic products; consolidation of our customer base and commercial alliances among our customers; delays in launches of new generic products; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; 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, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments, may result in a further downgrade of our credit ratings; and our inability to raise debt or borrow funds in amounts or on terms that are favorable to us;
• 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; effectiveness of our optimization efforts; our ability to attract, hire and retain highly skilled personnel; manufacturing or quality control problems; interruptions in our supply chain; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; challenges associated with conducting business globally, including political or economic instability, major hostilities or terrorism; 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; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; significant sales to a limited number of customers; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; and our prospects and opportunities for growth if we sell assets;
• compliance, regulatory and litigation matters, including: failure to comply with complex legal and regulatory environments; increased legal and regulatory action in connection with public concern over the abuse of opioid medications and our ability to reach a final resolution of the remaining opioid-related litigation; scrutiny from competition and pricing authorities around the world, including our ability to successfully defend against the U.S. Department of Justice criminal charges of Sherman Act violations; potential liability for patent infringement; product liability claims; failure to comply with complex Medicare and Medicaid reporting and payment obligations; compliance with anti-corruption sanctions and trade control laws; and environmental risks;
• other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; potential impairments of our intangible assets; potential significant increases in tax liabilities (including as a result of potential tax reform in the United States); and the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business;

and other factors discussed in this press release and in our Quarterly Report on Form 10-Q for the first quarter of 2021 and in our Annual Report on Form 10-K for the year ended December 31, 2020, including in the sections captioned "Risk Factors” and “Forward Looking Statements.” 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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