Phase 3 RISE study evaluated treatment with TV-46000, a subcutaneous long-acting injectable risperidone formulation

New data showed TV-46000 decreased risk of relapse and increased chance of clinical stability versus placebo in patients with schizophrenia

Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced results from the pivotal Phase 3 Risperidone Subcutaneous Extended-release (RISE) study comparing TV-46000/mdc-IRM once monthly (q1m) and TV-46000/mdc-IRM once every two months (q2m) with placebo (1:1:1) in patients with schizophrenia who underwent stabilization on oral risperidone. Results showed treatment with TV-46000 (overall, q1m or q2m) significantly prolonged time to relapse, decreased proportions of patients with impending relapse at week 24 and demonstrated significant increase in proportions maintaining stability. The safety profile of TV-46000, as demonstrated in this study, is consistent with other formulations of risperidone. The most common adverse reactions (≥5% and greater than placebo) were nasopharyngitis, increased weight, and extrapyramidal disorder. These findings, among others, were presented during the poster session at the 2021 Psych Congress Annual Meeting taking place Oct. 29-Nov. 1, 2021 in San Antonio, TX (in addition to virtual participation).

Schizophrenia is a chronic and severe mental disorder¹ characterized by distortions in thinking, perception, emotions, language, sense of self and behavior.² Twenty million people worldwide are affected by schizophrenia¹, often living with considerable disability.² Currently, about 70% of people living with schizophrenia are not receiving appropriate care³ despite the treatability of the illness.²

^“Relapse rates among people living with schizophrenia are quite staggering, ranging between 50 and 92% globally.^4,5 It is crucial to provide patients and prescribers with treatment options that have the potential to reduce relapse rates to help manage and stabilize the disease over time,” said Eran Harary, MD, VP Global Head of Specialty R&D at Teva. “Coming off the heels of the recent FDA acceptance of our New Drug Application, we’re proud to be sharing our Phase 3 data at this year’s Psych Congress. We are committed to investigating the full potential of our subcutaneous long-acting injectable (LAI) formulation of risperidone for the treatment of this complex and burdensome illness.”

“When managing schizophrenia, it is crucial to have treatment options that work to reduce the risk of relapse. As researchers, physicians and providers, we must work together to address this,” said John Kane, MD, Professor and Chairman, Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and RISE lead investigator. “These latest data from the Phase 3 RISE study are quite encouraging for both patients and providers.”

Efficacy and Safety of Subcutaneous Risperidone Injectable (TV-46000) in Patients With Schizophrenia: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Relapse Prevention Study (RISE Study)

The Phase 3 RISE study was designed to compare TV-46000 q1m and TV-46000 q2m with placebo (1:1:1 ratio; stage 2) in patients with schizophrenia who underwent stabilization on oral risperidone (stage 1). The primary endpoint was time to impending relapse and secondary endpoints included proportions of patients with impending relapse at week 24 and proportions of patients who maintained stability at week 24. No new safety signals were identified with TV-46000 versus accumulated safety data of oral risperidone and other long-acting risperidone formulations.

Out of 1267 patients screened, 863 were enrolled and 544 were randomized. Time to impending relapse significantly favored TV-46000 (hazard ratio [95% CI]; overall: 0.283 [0.184, 0.435], P<.0001; q1m: 0.200 [0.109, 0.367], P<.0001; q2m: 0.375 [0.227, 0.618], P<.0001) versus placebo. TV-46000 also prolonged time to relapse by 3.5, 5.0 and 2.7 times, respectively, versus placebo. Proportions of patients with impending relapse at week 24 were significantly lower for TV‑46000 (overall: 9%; q1m: 7%; q2m: 11%) versus placebo (28%; P<.0001, P<.0001, P=.0001, respectively). Proportions of patients maintaining stability were significantly higher (83%, 87%, 80% vs 61%; P<.0001, P<.0001, P=.0001, respectively). The safety profile of TV-46000, as observed in this study, is consistent with other formulations of risperidone. The most common adverse reactions (≥5% and greater than placebo) were nasopharyngitis, increased weight, and extrapyramidal disorder.

About TV46000-CNS-30072 (The RISE Study – The Risperidone Subcutaneous Extended-Release Study)

The RISE study was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of risperidone extended-release injectable suspension for subcutaneous use as a treatment in patients (ages 13-65 years) with schizophrenia. 544 patients were randomized to receive a subcutaneous injection of TV-46000 once monthly (q1M), once every two months (q2M), or placebo in a 1:1:1 ratio. The primary endpoint was time to impending relapse.

About Schizophrenia

Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts. Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability. Approximately 1% of the world’s population will develop schizophrenia in their lifetime, and 3.5 million people in the U.S. are currently diagnosed with the condition. Although schizophrenia can occur at any age, the average age of onset tends to be in the late teens to the early 20s for men, and the late 20s to early 30s for women. The long-term course of schizophrenia is marked by episodes of partial or full remission broken by relapses that often occur in the context of psychiatric emergency and require hospitalization. Approximately 80% of patients experience multiple relapses over the first five years of treatment, and each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology. Patients are often unaware of their illness and its consequences, contributing to treatment nonadherence, high discontinuation rates, and ultimately, significant direct and indirect healthcare costs from subsequent relapses and hospitalizations.

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, 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 the development of risperidone LAI; our ability to successfully compete in the marketplace, including 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; 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, 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; compliance, regulatory and litigation matters, including failure to comply with complex legal and regulatory environments; other financial and economic risks; and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2020, 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 GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. [published correction appears in Lancet. 2019 Jun 22;393 (10910):e44]. Lancet. 2018;392 (10159): 1789-1858.

² World Health Organization. Schizophrenia. www.who.int/news-room/fact-sheets/detail/schizophrenia. Accessed on October 4, 2021.

³ Lora A, et al. Service availability and utilization and treatment gap for schizophrenic disorders: a survey in 50 low- and middle-income countries. Bulletin of the World Health Organization. 90 (1), 47-54B. World Health Organization. http://dx.doi.org/10.2471/BLT.11.089284

⁴Cernansky JG, Schuchart EK. Relapse and rehospitalisation rates in patients with schizophrenia: effects of second generation antipsychotics CNS Drugs. 2002;16(7):473–484.

⁵Weret ZS, Mukherjee R. Prevalence of relapse and associated factors in patient with schizophrenia at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia: institution based cross sectional study. International Journal of Interdisciplinary and Multidisciplinary Studies. 2014, Vol 2, No.1, 184-192.

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