Teva’s New Real-World Evidence Presented at the 2024 AAN Annual Meeting Confirms Effectiveness and Patient Satisfaction for HD Chorea with the 4-week Titration Kit for AUSTEDO® (deutetrabenazine) Tablets

2024-04-16

临床结果临床3期上市批准

Almost 80% of patients with Huntington's disease (HD) chorea were able to achieve optimal dosing within four weeks with the 4-week Titration Kit in final START study results

START study results further support real-world effectiveness, safety, adherence and patient satisfaction with the 4-week Titration Kit for AUSTEDO

AUSTEDO remains the only vesicular monoamine transporter 2 (VMAT2) inhibitor available with 3-year data for this progressive condition1,2

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 final results from the HD cohort of the Phase 4 START study, demonstrating positive real-world effectiveness, safety, adherence and satisfaction with the 4-week Titration Kit for AUSTEDO. As a fatal, neurodegenerative disease, HD can cause cognitive deterioration, behavioral and/or psychological problems and uncontrollable body movements known as chorea – a symptom that can have a significant impact on daily activities like eating or talking.3-5 These data are being presented at the 2024 American Academy of Neurology (AAN) Annual Meeting.

“90% of HD patients experience chorea,3,4 so it’s important for patients to have a treatment option that not only helps address symptoms, but helps provide a positive patient experience,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “We remain committed to exploring ways to evolve the AUSTEDO treatment experience to meet the needs of the HD community, and these latest real-world data reinforce the role of the 4-week Titration Kit for AUSTEDO in empowering patients with HD chorea to find their optimal dose, adhere consistently to their treatment plan, and achieve effective outcomes.”

The START study was a Phase 4 study investigating real-world treatment outcomes for patients starting AUSTEDO with the 4-week Titration Kit. Final results from the HD cohort of the START study show that by week 24:

76% (13/17) of patients successfully completed the titration kit, with more than 90% adherence and a 33% mean reduction in total maximal chorea (TMC) score from baseline

53% (9/17) of patients achieved treatment success using the Clinical Global Impression of Change (CGIC) and 71% (12/17) using the Patient Global Impression of Change (PGIC)

100% (12/12) of patients who completed the satisfaction survey found the kit easy to use and 100% (7/7) of providers who completed the satisfaction survey found the kit helpful in ensuring patient adherence to the titration schedule

The safety profile of AUSTEDO in this study was consistent with the pivotal studies.

“These data demonstrate that we can have confidence in this treatment approach that allows patients to adjust their medication based on their individual HD chorea symptoms,” said Karen Anderson, MD, Professor, Psychiatry and Neurology at Georgetown University School of Medicine and Director, Huntington’s Disease Care, Education and Research Center. “I’m glad to see this outcome as it gives clinicians more confidence and patients more control.”

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.3 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.3,4 Chorea can have a significant impact on daily activities and progressively limit peoples’ lives.3

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,”

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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.libproxy1.nus.edu.sg/10.3389/fneur.2022.773999.

Frank, S., Testa, C., Edmondson, M.C. et al. The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study. CNS Drugs (2022). https://doi-org.libproxy1.nus.edu.sg/10.1007/s40263-022-00956-8.

Huntington’s Disease. National Institute of Neurological Disorders and Stroke. https://www-ninds-nih-gov.libproxy1.nus.edu.sg/health-information/disorders/huntingtons-disease#toc-what-is-huntington-s-disease-. Accessed April 16, 2024.

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.libproxy1.nus.edu.sg/10.1007/s40271-018-0312-x

Claassen DO, DeCourcy J, Mellor J, Johnston C, Iyer RG. Impact of chorea on self-care activity, employment, and health-care resource use in patients with Huntington's disease. JHEOR. 2021;8(1):99-105. doi:10.36469/jheor.2021.24620

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Source: Teva Pharmaceutical Industries Limited