Additional data to be presented examining the safety and tolerability of AUSTEDO during periods of titration and maintenance

Teva Neuroscience, Inc., an affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) will present new study data on AUSTEDO at the International Parkinson and Movement Disorder Society annual congress (MDS Virtual Congress 2020) and Psych Congress 2020 Virtual Experience evaluating the long-term efficacy and safety of AUSTEDO in patients with tardive dyskinesia (TD), and the safety and tolerability of AUSTEDO during periods of titration and maintenance in patients with TD.

“Tardive dyskinesia causes involuntarily, uncontrollable movements, that can have a significant impact on functioning and emotional well-being of those living with the condition,” said Daniel McBryan, M.D., Senior Vice President, Head of Global Medical Affairs and Pharmacovigilance at Teva. “The data being presented this year deepen our understanding of the risk-benefit profile of AUSTEDO over the long-term, in patients most severely impacted by TD, and provides context around the dosing schedule.”

Three Year Efficacy and Safety of AUSTEDO for Treatment of TD

The open-label extension of the pivotal ARM-TD and AIM-TD studies evaluated the long-term efficacy and safety of AUSTEDO for the treatment of TD. Treatment was titrated up to a maximum daily dose of 48 mg based on control of movements and medication tolerability and results were evaluated measuring change from baseline in Abnormal Involuntary Movement Scale (AIMS) scores and Clinical Global Impression of Change (CGIC). The following outcomes were recorded:

  • At Week 54 (n=249; total daily dose [mean±SE]: 38.7±0.66 mg), mean change from baseline in AIMS score was -4.8±0.28, and physician assessments reported 66% of patients met the “much improved” or “very much improved” scores on the CGIC.
  • At Week 106 (n=194; total daily dose: 39.3±0.75 mg), mean change from baseline in AIMS score was -5.4±0.33, and physician assessments reported 65% of patients met the “much improved” or “very much improved” scores on the CGIC.
  • At Week 145 (n=160; total daily dose: 39.4±0.83 mg), mean change from baseline in AIMS score was -6.6±0.37, and physician assessments reported 73% of patients met the “much improved” or “very much improved” scores on the CGIC.

No new safety signals were identified in this population that were inconsistent with the known safety profile of AUSTEDO.

Long-Term Efficacy and Safety of AUSTEDO In Patients Severely Impacted by TD

A post hoc analysis of the open-label extension portion of the pivotal ARM-TD and AIM-TD studies evaluated the efficacy of AUSTEDO in reducing TD in the most severely impacted patients. Using the upper quartile of baseline AIMS scores from the open-label extension, two subgroups were defined as having scores >14 or ≤14. At all-time points from Week two to Week 145, change from baseline in AIMS score was greater in those with baseline AIMS score >14 versus ≤14 (mean ±SE at Wk 145: -10.9±0.8, -5.1±0.3). Percent change from baseline in patients with AIMS score >14 reached -59.4%±3.6% versus -55.2%±3.1% for patients with AIMS score ≤14 at Week 145. The percent of patients with ≥50% AIMS reduction at each visit was 71% in patients with baseline AIMS score >14 versus 64% in patients with AIMS score ≤14 at Week 145.

No new safety signals were identified in this population that were inconsistent with the known safety profile of AUSTEDO.

Safety and Tolerability of AUSTEDO During Titration and Maintenance

The study evaluated data from the ARM-TD and AIM-TD studies and the open-label extension through week 15 to examine the safety and tolerability of AUSTEDO during titration and maintenance phases of therapy.

AE Rates for Fixed-Dose AUSTEDO (12 mg-36 mg groups; n=221), Flexible Dose AUSTEDO (n=169) & Placebo (n=131)

Phase

Dose Type

Overall AEs

Serious AEs

AEs Leading to Discontinuation

Treatment-related AEs

Titration

Fixed

32.4–40.5%

2.7–6.8%

2.7–5.4%

8.1–16.2%

Flexible

49.1%

3.6%

2.4%

31.4%

Placebo

42.7%

4.6%

3.1%

26.7%

Maintenance

Fixed

21.9–28.4%

0–1.4%

0%

8.2–13.5%

Flexible

32.5%

2.4%

1.2%

12.4%

Placebo

25.2%

2.3%

0%

9.9%

Common AEs for Fixed Dose AUSTEDO (12 mg–36 mg groups)

 

Headache

Diarrhea

Nasopharyngitis

Depression

Hypertensions

Dry Mouth

Titration

2.7–6.8%

1.4–5.4%

1.4–4.1%

0–4.1%

0–4.1%

0–4.1%

Maintenance

0–4.1%

0%

0%

0%

0%

0%

For flexible-dose AUSTEDO, the only common AE during titration was somnolence (11.2%); there were no common AEs during maintenance. Rates of specific AEs in titration and maintenance were (ranges for all groups in both periods: parkinsonism, 0–1.4%; suicidal ideation, 0–2.7%; akathisia, 0–1.8%; restlessness, 0–1.4%).

Common AEs for Placebo

 

Somnolence

Headache

Nausea

Fatigue

Dry Mouth

Titration

6.9%

6.1%

5.3%

4.6%

4.6%

Maintenance

0%

0%

0%

0%

0%

All abstracts presented at MDS Virtual Congress 2020 will be published in the Movement Disorders journal e-supplement and displayed as an e-poster in the 2020 Virtual Poster. Abstracts at the Psych Congress 2020 Virtual Experience will be available online in the virtual exhibit hall.

About AUSTEDO® (deutetrabenazine)

AUSTEDO® is a 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. Safety and effectiveness in pediatric patients have not been established.

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: Tetrabenazine, a closely related VMAT2 inhibitor, causes an increase in the corrected QT (QTc) interval. A clinically relevant QT prolongation may occur in some patients treated with AUSTEDO® who are CYP2D6 poor metabolizers or are co-administered a strong CYP2D6 inhibitor. Dose reduction may be necessary. The use of AUSTEDO® in combination with other drugs known to prolong QTc may result in clinically significant QT prolongations. For patients requiring AUSTEDO® doses greater than 24 mg per day who are using AUSTEDO® with other drugs known to prolong QTc, assess the QTc interval before and after increasing the dose of AUSTEDO® or the other drugs. 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.

CYP2D6 Metabolism: In patients who are poor CYP2D6 metabolizers or are taking strong CYP2D6 inhibitors, the total daily dosage of AUSTEDO® should not exceed 36 mg (maximum single dose of 18 mg).

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 2,400 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; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; competition for our specialty products, especially COPAXONE®, our leading medicine, which faces competition from existing and potential additional generic versions, competing glatiramer acetate products and orally-administered alternatives; the uncertainty of commercial success of AJOVY® or AUSTEDO®; competition from companies with greater resources and capabilities; delays in launches of new products and our ability to achieve expected results from investments in our product pipeline; ability to develop and commercialize biopharmaceutical products; efforts of pharmaceutical companies to limit the use of generics, including through legislation and regulations 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 magnitude, duration, and geographic reach of the COVID-19 pandemic and its impact on our business, financial condition, operations, cash flows, and liquidity and on the economy in general; interruptions in our supply chain, including due to potential effects of the COVID-19 pandemic on our operations and business in geographic locations impacted by the pandemic and on the business operations of our customers and suppliers; adequacy of and 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 restructuring plan announced in December 2017; challenges associated with conducting business globally, including adverse effects of the COVID-19 pandemic, political or economic instability, major hostilities or terrorism; our ability to attract, hire and retain highly skilled personnel; our ability to develop and commercialize additional pharmaceutical products; compliance with anti-corruption sanctions and trade control laws; manufacturing or quality control problems; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; 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; our prospects and opportunities for growth if we sell assets and potential difficulties related to the operation of our new global enterprise resource planning (ERP) system;
  • compliance, regulatory and litigation matters, including: our ability to successfully defend against the DOJ criminal charges of a Sherman Act violations; increased legal and regulatory action in connection with public concern over the abuse of opioid medications in the U.S. and our ability to reach a final resolution of the remaining opioid-related litigation; costs and delays resulting from the extensive governmental regulation to which we are subject or delays in governmental processing time including due to modified government operations due to the COVID-19 pandemic and effects on product and patent approvals; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; governmental investigations into S&M practices; potential liability for patent infringement; product liability claims; increased government scrutiny of our patent settlement agreements; failure to comply with complex Medicare and Medicaid reporting and payment obligations; 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; 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 our Quarterly Reports on Form 10-Q for the first and second quarters of 2020 and our Annual Report on Form 10-K for the year ended December 31, 2019, 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.

IR United States Kevin C. Mannix (215) 591-8912 Ran Meir 972 (3) 926-7516 PR United States Doris Li (973) 265-3752 Israel Yonatan Beker 972 (54) 888 5898

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