TEV Teva Pharmaceutical Industries Ltd

Teva Presents New Phase 3 Efficacy, Safety and Tolerability Data from SOLARIS Trial Evaluating TEV-‘749 (olanzapine) as a Once-Monthly Subcutaneous Long-Acting Injectable for Adult Patients Diagnosed with Schizophrenia

• As a leader in neuroscience, Teva is committed to researching new treatment innovations that may help address unmet needs in treating schizophrenia, including TEV-‘749
• Currently, there is no long-acting olanzapine treatment option available for the treatment of schizophrenia that does not contain a boxed warning for Post-Injection Delirium/Sedation Syndrome (PDSS)
• New Phase 3 SOLARIS and Phase 1 safety data show no incidence of PDSS in study participants receiving TEV-‘749 to date
  

TEL AVIV, Israel & PARSIPPANY, N.J., Sept. 21, 2024 (GLOBE NEWSWIRE) -- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced new positive efficacy, safety and tolerability results for Phase 3 Subcutaneous Olanzapine Extended-Release Injection Study (SOLARIS) trial evaluating TEV-‘749 in adult patients diagnosed with schizophrenia. In the study, TEV-‘749 met the primary endpoint, demonstrating significant improvements in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8, as well as key secondary endpoints with improvements in both the Clinical Global Impression-Severity (CGI-S) scale and the Personal and Social Performance (PSP) scale score, compared to placebo at week 8. Additionally, SOLARIS (Period 1) and Phase 1 safety results demonstrated no incidence of post-injection delirium/sedation syndrome (PDSS) in participants taking TEV-‘749 to date.¹ The overall safety profile was consistent with other oral acting olanzapine options. These data were presented during the 37th Annual European College of Neuropsychopharmacology (ECNP) Congress taking place between September 21-24, 2024, in Milan, Italy.

Schizophrenia is a complex medical condition that may require switching from oral options or between different long-acting injectable (LAI) options during the patient treatment journey. These data demonstrate the potential role of TEV-‘749 as an LAI treatment option for schizophrenia patients taking daily oral olanzapine or other antipsychotic medications. Currently, the only long-acting olanzapine treatment option for schizophrenia carries a risk for PDSS, the sudden and unexpected onset of delirium or sedation when medication is released too quickly into the blood after receiving an intramuscular injection of long-acting olanzapine.¹

“Teva is dedicated to building on its commitment to neuroscience by developing new long-acting injectable treatment options like TEV-‘749 that may help address unmet needs in schizophrenia for patients and healthcare providers,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “PDSS is a major barrier to the utilization of intramuscular olanzapine LAIs that exists today, and our SOLARIS findings fuel the continued development of TEV-‘749.”

With nearly 30 years of clinical and real-world use, olanzapine is one of the most commonly prescribed 2^nd generation oral antipsychotics for schizophrenia around the world. Its efficacy and safety profiles are well established.

“Developing a long-acting olanzapine formulation that poses potentially no risk of PDSS is crucial in preventing these dangerous episodes that otherwise limit the use of olanzapine to daily oral options,” said Christoph Correll, MD, Professor of Psychiatry at the Zucker School of Medicine, Hempstead, NY. “With no PDSS observed in the SOLARIS trial to date, these data add to the growing body of evidence that TEV-‘749 may one day serve as an important treatment option for patients and healthcare providers who rely on olanzapine and also have needs or preferences that require a long-acting option.”

Period 1 of the SOLARIS study is an 8-week, randomized, double-blind, placebo-controlled trial in patients aged 18-64 years diagnosed with schizophrenia, followed by an open-label safety period of up to 48 weeks (Period 2). Efficacy results from Period 1 of the SOLARIS study show that by week 8:

• TEV-‘749 met its primary endpoint across all three dosing groups, with statistically significant mean differences in the change in PANSS total scores from baseline to week 8 of -9.71 points, -11.25 points, and -9.69 points versus placebo for the high (531 mg, corresponding to 20 mg/day of oral olanzapine), medium (425 mg, corresponding to 15 mg/day of oral olanzapine), and low (318 mg, corresponding to 10 mg/day of oral olanzapine) dose groups, respectively (all P<0.0001).¹
• TEV-‘749 treatment significantly improved CGI-S scale scores across all three dosing groups, with reductions of -0.47 points (high), -0.61 points (medium), and -0.53 points (low) versus placebo from baseline to week 8 (all P<0.0001).¹
• TEV-‘749 treatment significantly improved PSP scale scores across all three dosing groups, with increases of 4.93 points (high), 3.15 points (medium), and 4.63 points (low) versus placebo from baseline to week 8 (all P<0.02).¹
  

The systemic safety profile of TEV-‘749 was consistent with other approved formulations of olanzapine, with no new safety signals identified. Additional safety and tolerability results from Period 1 (917 active injections) through week 8 of the SOLARIS study show that:

• There were no reported cases of PDSS.¹
• Treatment-emergent adverse events that occurred more often in patients receiving TEV-‘749 versus placebo included weight increase (35% [173/500] versus 8% [13/167]), injection site induration (13% [64/500] versus 2% [4/167]), injection site pain (10% [50/500] versus 4% [7/167]) and injection site erythema (10% [48/500] versus 1% [1/167]).¹
• Serious adverse events and discontinuations due to adverse events were reported in 1% (7/500) and 3% (16/500) of patients treated with TEV-‘749, respectively, and in 2% (3/167) and 3% (5/167) of patients treated with placebo, respectively.¹
  

Also presented at ECNP 2024, results from the Phase 1 study of TEV-'749 show similar safety and tolerability results, including no reports of PDSS events. Additionally, a presented pre-clinical study suggests that the subcutaneous route of administration and formulation characteristics of TEV-'749 appear to greatly reduce the hypothesized risk of PDSS occurrence for patients receiving the treatment.

The long-term safety of TEV-‘749 and incidence of PDSS are also being evaluated in the SOLARIS open-label study (Period 2), with safety data topline readout expected in the first half of 2025.

TEV-‘749 utilizes SteadyTeq™, a copolymer technology proprietary to Medincell that provides a controlled steady release of olanzapine.

TEV-‘749 is an investigational once-monthly subcutaneous LAI of the 2^nd generation antipsychotic olanzapine and is not approved by any regulatory authority for any use, and its safety and efficacy are not established.

About Subcutaneous OLAnzapine Extended-Release Injection Study (SOLARIS)
SOLARIS is a multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of olanzapine extended-release injectable suspension for subcutaneous use as a treatment in patients (ages 18-65 years) with schizophrenia. For period one of the study (first 8 weeks), 675 patients were randomized to receive a subcutaneous injection of once-monthly TEV-‘749 (low, medium or high dose) or placebo in a 1:1:1:1 ratio. For period two, which will last for up to 48 weeks, patients who completed period one were randomized and equally allocated to one of the three TEV-‘749 treatment groups. The end-of-treatment and follow-up visits will be at 4 and 8 weeks after administration of the last treatment dose, respectively. The primary objective of the Phase 3 SOLARIS study was to evaluate the efficacy of TEV-‘749 in adult patients with schizophrenia. A key secondary objective was to further evaluate the efficacy of TEV-‘749 based on additional parameters in adult patients with schizophrenia. A secondary objective that is still ongoing through period two of the study is to evaluate the safety and tolerability of TEV-‘749 in adult patients with schizophrenia.

About Schizophrenia
Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts.¹ Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability.^1,2,3 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.^2,3 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.³ 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.³ 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.^4,5,6 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.^1,2,3,4,5,6

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.

About Medincell
Medincell is a clinical- and commercial-stage biopharmaceutical licensing company developing long-acting injectable drugs in many therapeutic areas. Our innovative treatments aim to guarantee compliance with medical prescriptions, to improve the effectiveness and accessibility of medicines, and to reduce their environmental footprint. They combine active pharmaceutical ingredients with our proprietary BEPO^® technology which controls the delivery of a drug at a therapeutic level for several days, weeks or months from the subcutaneous or local injection of a simple deposit of a few millimeters, entirely bioresorbable. The first treatment based on BEPO^® technology, intended for the treatment of schizophrenia, was approved by the FDA in April 2023, and is now distributed in the United States by Teva under the name UZEDY^® (BEPO^® technology is licensed to Teva under the name SteadyTeq™). We collaborate with leading pharmaceutical companies and foundations to improve global health through new treatment options. Based in Montpellier, Medincell currently employs more than 140 people representing more than 25 different nationalities. www.medincell.com

Note: TEV-‘749 is referenced as mdc-TJK in Medincell’s documentation and corporate website.

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 olanzapine LAI (TEV-‘749) for the treatment of adults with schizophrenia; our ability to achieve successful results from the Phase 3 trial for olanzapine LAI (TEV-‘749), including the efficacy and safety portions; 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 profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development; the effectiveness of our patents and other measures to protect our intellectual property rights; 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 Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
² Substance Abuse and Mental Health Services Administration. Schizophrenia. https://www.samhsa.gov/mental-health/schizophrenia. Accessed November 2023.
³ Velligan DI, Rao S. The epidemiology and global burden of schizophrenia. J Clin Psychiatry. 2023;84(1):MS21078COM5. https://doi.org/10.4088/JCP.MS21078COM5  
⁴ Wander C. (2020). Schizophrenia: opportunities to improve outcomes and reduce economic burden through managed care. The American journal of managed care, 26(3 Suppl), S62–S68. https://doi.org/10.37765/ajmc.2020.43013
⁵ Emsley, R., & Kilian, S. (2018). Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review. Neuropsychiatric disease and treatment, 14, 205–223.
⁶ Emsley, R., Chiliza, B., Asmal, L. et al. (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13, 50.

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