TEVA Teva Pharmaceutical Industries Ltd

Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced new patient- and physician-reported interim results from the Phase 4 IMPACT-TD Registry study, revealing differences between TD patients with a psychotic disorder and those with a mood disorder. The IMPACT-TD Registry is the largest study of its kind evaluating the holistic effects of TD, showing real-world treatment patterns and outcomes with once-daily AUSTEDO® XR® (deutetrabenazine) extended-release tablets and twice-daily AUSTEDO (deutetrabenazine) tablets. Teva also announced interim data from a patient-reported survey describing early, real-world experience with AUSTEDO XR. These findings are being presented at the Psych Congress 2024 taking place from October 29 – November 2 in Boston, MA.

“Tardive dyskinesia is underdiagnosed and often little-understood while presenting a major negative impact on all aspects of a patient’s life. Our latest research is part of Teva’s efforts to build better outcomes, as we seek to improve the day-to-day lives of the patients we serve,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “As we continue driving meaningful innovation and lead efforts to tackle mental health equity gaps in care, we are steadfastly committed to understanding the experience of those who are living with TD and look forward to additional insights as we continue this registry.”

The two-part IMPACT-TD study is a three-year longitudinal observational study evaluating how TD progresses and impacts a patient’s quality of life, as well as outcomes related to treatment with once-daily AUSTEDO XR and twice-daily AUSTEDO. The study includes adult patients identified to have TD, but a formal TD diagnosis was not required to participate.

The IMPACT-TD findings revealed:

• Fewer people with a psychotic disorder had received a diagnosis of TD compared to those with mood disorders (36% vs 50%), despite having similar mean AIMS scores (8.7 vs 8.0), a longer median time since the first recognition of movements (5.5 vs 3.8 years), and a longer median time since the first use of an antipsychotic (16 vs 10 years)
• In the study, patients with a psychotic disorder (n=135) compared to those with a mood disorder (n=141) were younger (mean age 48 vs 55.5), more likely to be Black or African American (36% vs 9%), and male (62% vs 38%)
• The impact of TD on the lives of patients in the study was similar in both groups, with clinicians reporting moderate or severe impact of 86% for those with a psychotic disorder and 80% for those with mood disorders

“It is critical for people with psychotic disorders to get the treatment that they need. In the past several years, antipsychotic medicines use has increased, leading to an increased risk of developing TD,” said Rakesh Jain, MD, MPH, Clinical Professor of Psychiatry, Texas Tech University School of Medicine – Permian Basin. “Taken together, the results of this physician- and patient-reported data reveal the need to more closely monitor patients suffering from mental health conditions for signs of TD so that they can be treated early and effectively.”

Teva also presented findings on real-world patient experience with AUSTEDO XR from a non-interventional, prospective, cross-sectional survey, which included adults with TD or Huntington’s disease (HD) chorea who were prescribed the medication. The survey explored patient-reported ease of use, effectiveness and satisfaction. In this interim analysis of data from 131 respondents:

• 87% reported satisfaction with the medication overall
• 74% reported that their extra movements improved with AUSTEDO XR
• More than 76% agreed that a reduction in their extra movements had improved their comfort in social settings and their emotional well-being, and more than half of patients agreed that a reduction in their extra movements had improved their overall physical health and work or school/life balance since starting the medication
• Almost all respondents (98%) reported that AUSTEDO XR was easy to use and incorporate into daily routines and agreed that they would continue to take it (95%)

Currently more than 57 million Americans are living with a mental illness, 14 million of whom are living with a serious mental health condition.1 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.2,3 Both TD and HD chorea can pose significant challenges to patients’ every day lives as simple tasks like eating, talking and walking can be impacted.

About Tardive Dyskinesia (TD)

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.4,5,6

About Chorea Associated with Huntington’s Disease (HD)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.7,8

About AUSTEDO XR Extended-Release Tablets and AUSTEDO TabletsAUSTEDO 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 USAGEAUSTEDO 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 TD.

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 TevaTeva 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 StatementsThis 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; and other factors discussed in our Quarterly Report on Form 10-Q for the second 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. 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.
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3. 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.
4. 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.
5. Waln O, Jankovic J. An Update on Tardive Dyskinesia: From Phenomenology to Treatment. Tremor Other Hyperkinet Mov. 2013;3:1-11.
6. Tardive dyskinesia. National Alliance on Mental Illness website. https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Tardive-Dyskinesia. Accessed May 4, 2023.
7. 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.
8. 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.

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