Teva Announces AUSTEDO® XR (deutetrabenazine) Extended-Release Tablets Now U.S. FDA Approved as a One Pill, Once-Daily Treatment Option for Clinically Therapeutic Doses (24–48 mg/day)

  • U.S. FDA approves new one pill, once-daily AUSTEDO XR tablets (30, 36, 42, 48 mg/day)
  • AUSTEDO XR offers more flexibility with the most once-daily doses of any vesicular monoamine transporter 2 (VMAT2) inhibitor for effective and tolerable tardive dyskinesia (TD) and Huntington’s disease (HD) chorea control1
  • Patients with TD taking AUSTEDO XR can expect symptom improvement as early as two weeks while patients with HD chorea may experience a significant reduction in Total Maximal Chorea (TMC) score, with three years of the longest TD and HD chorea clinical trials and sustained results to date 1,2,3,4,5

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 that the U.S. Food and Drug Administration (FDA) has approved AUSTEDO XR as a one pill, once-daily treatment option, now with four new tablet strengths (30, 36, 42, 48 mg) indicated in adults for TD and HD chorea.

“Since our launch of AUSTEDO® in 2017, we have been committed to helping people living with TD and HD chorea treat these chronic, involuntary movements,” said Dell Faulkingham, Senior Vice President, Head of U.S. Innovative Medicines at Teva. “AUSTEDO, backed by the longest efficacy and tolerability data to date, has continued to evolve – having received approval for AUSTEDO XR, our once-daily extended-release formulation in February 2023. This latest milestone offers a streamlined treatment regimen for clinically therapeutic doses with the broadest dosing flexibility.”

Currently more than 57 million Americans are living with a mental illness, 14 million of whom are living with a serious mental health condition.6 For those taking certain mental health medications, one in four may experience the onset of TD, an often-overlooked chronic movement disorder that can have a physical, emotional and psychological impact on patients.7,8 HD is a fatal neurodegenerative disease characterized by cognitive deterioration, behavior and/or psychological problems and uncoordinated and uncontrollable movements known as chorea – a symptom that affects 90% of patients.9,10 Both conditions can pose significant challenges to patients’ everyday lives as simple tasks like eating, talking and walking can be impacted.

“Knowing patients living with TD and HD chorea are also managing other underlying concomitant conditions, it is important that treatment options for these chronic movement disorders are not only effective, but keep the patient experience in mind,” said Dr. Rakesh Jain, Clinical Professor of Psychiatry, Texas Tech University School of Medicine. “This latest AUSTEDO XR approval provides patients with the same proven efficacy, but now with the convenience of a one pill, once-daily option for clinically therapeutic doses as established by the pivotal clinical trials to help control involuntary movements that can make carrying out basic daily activities difficult."

Patients with TD taking AUSTEDO XR can expect symptom improvement as early as two weeks while patients with HD chorea may experience a significant reduction in TMC score, with three years of the longest TD and HD chorea clinical trials and sustained results to date.1,2,3,4,5 AUSTEDO XR, along with its twice-daily counterpart, AUSTEDO (deutetrabenazine), are the only VMAT2 inhibitor treatments with no restrictions for use with CYP3A4/5 inducers or inhibitors, an important consideration for patients who take a variety of concomitant medications to manage their underlying conditions.11,12

Approximately 90% of patients with insurance coverage are expected to pay $10 or less for their prescription with financial assistance offerings.1 Teva is committed to helping eligible patients who have been prescribed AUSTEDO XR access their medication. Teva continues to support with access, reimbursement, prescription pull-through and patient assistance. Savings on out-of-pocket costs may vary depending on the patient’s insurance provider and eligibility for participation in the co-pay assistance program. For more information regarding cost and coverage options for AUSTEDO XR through Teva Shared Solutions, visit MySharedSolutions.com.

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. 13,14,15

About Chorea Associated with Huntington’s Disease (HD)
Huntington’s disease (HD) is a fatal neurodegenerative disease characterized by uncoordinated and uncontrollable movements, cognitive deterioration and behavioral and/or psychological problems. Chorea – involuntary, random and sudden, twisting and/or writhing movements – is one of the most striking physical manifestations of Huntington’s disease and occurs in approximately 90% of patients. Chorea can have a significant impact on daily activities and progressively limit peoples’ lives. 9,10

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 AUSTEDO and AUSTEDO XR for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease; our ability to successfully compete in the marketplace, including our ability to develop and commercialize additional pharmaceutical products; 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 to sustain and focus our portfolio of generics medicines; and other factors discussed in our Quarterly Report on Form 10-Q for the first quarter of 2024 and in our Annual Report on Form 10-K for the year ended December 31, 2023, 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 Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
2 Hauser, R. A., Barkay, H., Fernandez, H. H. et al. Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia is Associated with Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study. Frontiers in Neurology (2022). https://doi.org/10.3389/fneur.2022.773999.
3 Anderson K. E., Stamler D., Davis M. D., et al. Deutetrabenazine for the treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Psychiatry. 2017;4(8):595-604
4 Fernandez HH, Factor SA, Hauser RA, et al. Randomised controlled trial of deutetrabenazine for tardive dyskinesia: the ARM-TD study. Neurology. 2017;88(21):2003-2010.
5 Marder S. R., Singer C., Lindenmayer J-P., et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol. 2019;39(6)620-627.
6 U.S. Department of Health and Human Services. (n.d.). Mental illness. National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/mental-illness.
7 Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264-e278.
8 Hansen TE, Brown WL, Weigel RM, Casey DE. Underrecognition of tardive dyskinesia and drug-induced parkinsonism by psychiatric residents. Gen Hosp Psychiatry. 1992;14(5):340-344.
9 Huntington’s Disease. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease#toc-what-is-huntington-s-disease-. Accessed May 15, 2023.
10 Thorley, E. M., Iyer, R. G., Wicks, P., Curran, C., Gandhi, S. K., Abler, V., Anderson, K. E., & Carlozzi, N. E. (2018). Understanding How Chorea Affects Health-Related Quality of Life in Huntington Disease: An Online Survey of Patients and Caregivers in the United States. The patient, 11(5), 547–559. https://doi.org/10.1007/s40271-018-0312-x
11 AUSTEDO® XR (deutetrabenazine) extended-release tablets and AUSTEDO® (deutetrabenazine) tablets [current approved prescribing information].Parsippany, NJ: Teva Neuroscience, Inc
12 AUSTEDO® (deutetrabenazine) tablets current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.
13 Warikoo N, Schwartz T, Citrome L. Tardive dyskinesia. In: Schwartz TL, Megna J, Topel ME, eds. Antipsychotic Drugs. Hauppauge, NY: Nova Science Publishers. 2013:235-258.
14 Waln O, Jankovic J. An Update on Tardive Dyskinesia: From Phenomenology to Treatment. Tremor Other Hyperkinet Mov. 2013;3:1-11.
15 Tardive dyskinesia. National Alliance on Mental Illness website. https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Tardive-Dyskinesia. Accessed May 15, 2023.

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