olanzapine LAI (TEV-'749) / Teva, MedinCell, Royalty - LARVOL DELTA

New Data Strengthens Teva’s Schizophrenia Portfolio, Including Phase 3 SOLARIS Trial Survey Results Demonstrating Patient and Healthcare Professional Satisfaction with TEV-'749 (olanzapine) as a Once-Monthly Subcutaneous Long-Acting Injectable (GlobeNewswire) - P3 | N=70 | "Teva Pharmaceuticals...announced the presentation of a patient and healthcare professional (HCP) attitudes and experiences survey study, complementing the successful Phase 3 Subcutaneous Olanzapine Extended-Release Injection Study (SOLARIS) evaluating TEV-'749. More than 92% of patients, 87% of nurses and 72% of physicians were either satisfied or very satisfied when asked about TEV-'749, overall, including initiation regimen, monthly dosing schedule and dosing options...Post-injection monitoring requirements: Despite reporting low levels of social, emotional, financial or time impact, nearly all patients noted it would be helpful to have an LAI without a post-injection monitoring period (90.0%) or caregiver accompaniment requirement (92.9%)....Dosing schedule: A majority of participants valued a monthly dosing schedule “a lot” (patients: 61.4%; physicians: 72.7%; nurses: 66.7%)."

P3 data • Schizophrenia

New Data Strengthens Teva’s Schizophrenia Portfolio... (GlobeNewswire) - "Below is the full set of schizophrenia data presented by Teva at SIRS 2025: TEV-'749 (olanzapine): (De novo) Patient and healthcare professional attitudes and trial experiences with a subcutaneous long-acting injectable olanzapine (TV-44749) for the treatment of schizophrenia; UZEDY (risperidone): (De novo) Predictors of response and non-response to treatment for schizophrenia: machine learning analysis of patients treated with TV-46000 or placebo in the RISE study; Schizophrenia Treatment Landscape: (De novo) Healthcare professionals’ attitudes toward use of long-acting injectable antipsychotics for schizophrenia treatment differ among settings of care: ADVANCE survey results; (De novo) The evolving schizophrenia treatment landscape in the United States: A real-world claims analysis of treatment patterns and use of long-acting injectable antipsychotics; (De novo) Real-world antipsychotic prescription patterns among patients with schizophrenia in Australia:..."

Clinical data • Schizophrenia

Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Trial completion date: Jan 2025 ➔ Jun 2025 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Open-label Trial Characterizing the PK of 3 SC Olanzapine Extended-release Formulations in Participants With Schizophrenia/Schizoaffective Disorder (clinicaltrials.gov) - P1 | N=91 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

SOLARIS: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy and Safety of TV-44749 in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=675 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

Open-label Trial Characterizing the PK of 3 SC Olanzapine Extended-release Formulations in Participants With Schizophrenia/Schizoaffective Disorder (clinicaltrials.gov) - P1 | N=95 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Psychiatry • Schizophrenia

Long-acting subcutaneous injectable olanzapine (TV-44749) demonstrates efficacy in patients with schizophrenia: Results from a randomised, double-blind, placebo-controlled trial (SOLARIS) (ECNP 2024) - P3 | "The Subcutaneous OLAnzapine extended-Release Injection Study (SOLARIS; NCT05693935) is an ongoing phase 3 study designed to assess the efficacy, safety and tolerability of TV-44749 in patients with schizophrenia. In patients with schizophrenia, once-monthly subcutaneous TV-44749 demonstrated significantly greater efficacy versus placebo with no reported PDSS. TV-44749 may provide an effective LAI olanzapine formulation while avoiding the risk of PDSS and will be further studied in the open-label, long-term safety period of SOLARIS."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Voice digital biomarker as a potential tool for monitoring symptom severity for patients with schizophrenia and schizoaffective disorder (ECNP 2024) - "The first study was an open-label, single- and multiple-dose study including patients with schizophrenia or schizoaffective disorder to assess the safety, tolerability, and pharmacokinetics of TV-44749... Findings from 2 studies demonstrated a strong correlation between PANSS scores and voice parameters in patients with schizophrenia or schizoaffective disorder. Voice digital biomarkers offer a unique opportunity for providing continuous remote monitoring and predictive analytics for relapses and treatment adherence, alongside support and validation for human subjective assessments in clinical trials. Further study in larger sample sizes is warranted."

Biomarker • Clinical • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Population pharmacokinetic model- and simulation-based dose selection for a phase 3 trial of subcutaneous long-acting olanzapine in adults with schizophrenia (ECNP 2024) - P3 | "TV-44749 is a long-acting subcutaneous (sc) injectable formulation of olanzapine based on a novel copolymer drug delivery technology that ensures a controlled release of olanzapine...These doses demonstrated comparable exposure to daily oral olanzapine doses of 10mg, 15mg and 20mg/day, respectively, over a 1-month interval and resulted in simulated D2RO within 60–80%. These doses were subsequently selected and are being tested in the ongoing phase 3 study."

Clinical • P3 data • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Safety and tolerability of TV-44749: Results from a randomised, placebo-controlled phase 3 trial in patients with schizophrenia (SOLARIS) (ECNP 2024) - P3 | "The Subcutaneous OLAnzapine extended-Release Injection Study (SOLARIS; NCT05693935) is an ongoing phase 3 study designed to assess the efficacy, safety and tolerability of TV-44749 in patients with schizophrenia. Results from Period 1 of the SOLARIS trial indicate that the safety profile of TV-44749 was consistent with other approved formulations of olanzapine, no new safety signals were identified, and there were no reported cases of PDSS. Safety and tolerability will be further investigated in the open-label, long-term safety period of SOLARIS."

Clinical • P3 data • CNS Disorders • Psychiatry • Schizophrenia

A long-acting subcutaneous injectable formulation of olanzapine is designed to eliminate the causes of post-injection delirium/sedation syndrome (ECNP 2024) - "Introduction Use of the intramuscular (im) formulation of olanzapine (Zyprexa Relprevv, Eli Lilly) has been limited because of a black-box warning of post-injection delirium sedation syndrome (PDSS) and associated REMS. Overall the sc route of administration and formulation characteristics of TV-44749 appear to eliminate the causes of PDSS. These Results are further supported by the lack of PDSS events in the phase 1 study."

CNS Disorders • Psychiatry • Schizophrenia

Olanzapine for extended-release injectable suspension (TV-44749) for subcutaneous use demonstrated to be robust to extreme injection site manipulations in rats (ECNP 2024) - "ConclusionsOlanzapine for extended-release injectable suspension (TV-44749) for subcutaneous use has been developed to have an extended-release profile and minimal risk of dose dumping. Extreme manipulation of the TV-44749 injection site, either by heating or rubbing 30 minutes or 4 hours post-injection did not have any effect on the PK of olanzapine in rats, supporting the Conclusion that dose dumping with this product is unlikely."

Preclinical • CNS Disorders

Medincell’s partner Teva provides update on pivotal clinical Phase 3 of investigational Olanzapine Long-Acting Injectable (LAI) and UZEDY commercial progress (Businesswire) - P3 | N=675 | SOLARIS (NCT05693935) | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | "Olanzapine LAI (mdc-TJK): No PDSS observed after completion of c.95% of the targeted injections for submission; Full phase 3 safety results on track for H2 2024. UZEDY: Reaffirming revenue guidance for 2024: c.$80 million; Exploring an additional indication for UZEDY for the treatment of Bipolar I Disorder in adults."

P3 data • Sales • CNS Disorders • Schizophrenia

Teva and Medincell Announce Positive Phase 3 Efficacy Results from SOLARIS Trial Evaluating TEV-‘749 (olanzapine) as a Once-Monthly Subcutaneous Long-Acting Injectable in Adults with Schizophrenia (Businesswire) - P3 | N=675 | SOLARIS (NCT05693935) | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | "Teva Pharmaceuticals...and Medincell...announced results from the efficacy portion of the Phase 3 Subcutaneous OLAnzapine extended-Release Injection Study (SOLARIS) trial evaluating TEV-‘749 in adult patients with schizophrenia compared to placebo. Results demonstrated that TEV-‘749 met its primary endpoint as measured by a change in the PANSS total score from baseline after 8 weeks compared to placebo....TEV-‘749 met its primary endpoint across all three dosing groups, with mean difference in change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8 of -9.71 points, -11.27 points, and -9.71 points versus placebo for the high, medium, and low dose groups, respectively. These differences from placebo were clinically meaningful and statistically significant with adjusted P-values of <0.001 for each comparison."

P3 data • CNS Disorders • Schizophrenia

SOLARIS: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy and Safety of TV-44749 in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=675 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Trial completion date: Oct 2025 ➔ Jan 2025 | Trial primary completion date: Oct 2024 ➔ Mar 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Open-label Trial Characterizing the PK of 3 SC Olanzapine Extended-release Formulations in Participants With Schizophrenia/Schizoaffective Disorder. (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

An Open-Label Trial to Assess the Comparative Bioavailability of TV-44749 to Oral Olanzapine in Participants With Schizophrenia (clinicaltrials.gov) - P1 | N=116 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Open-label Trial Characterizing the PK of 3 SC Olanzapine Extended-release Formulations in Participants With Schizophrenia/Schizoaffective Disorder. (clinicaltrials.gov) - P1 | N=95 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

An Open-Label Trial to Assess the Comparative Bioavailability of TV-44749 to Oral Olanzapine in Participants With Schizophrenia (clinicaltrials.gov) - P1 | N=116 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

Population Pharmacokinetic Modeling Following Administration of Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use to Support Dose Selection for Phase 3 Clinical Trial (SOLARIS) (SIRS 2024) - "The olanzapine concentration-time profile observed following oral administration was best described using a two-compartment model. The olanzapine concentration-time profiles observed after TV-44749 sc injections showed complex kinetics characterized by a double Weibull input function representing two phases of drug release: a first phase associated with an initial immediate release of a fraction of the dose, and a second phase associated with a delayed and sustained release of a second fraction of the dose. Final Pop-PK model estimates suggests the immediate first phase, with initial release of 23.6% of the associated dose (FF) peaking (TD=63.2% release) at 5 days post-dose."

Clinical • P3 data • PK/PD data • CNS Disorders • Schizophrenia • DRD2

TV-44749, A Long-Acting Subcutaneous (sc) Injectable Formulation of Olanzapine is Designed to Provide Sustained Controlled Concentrations and to Eliminate the Causes of Post-Injection Delirium/Sedation Syndrome (PDSS) (SIRS 2024) - "The results show that both APIs were stable in human plasma, however, olanzapine base in crystalline form II in TV-44749 showed 1.8 times lower solubility than olanzapine pamoate monohydrate of the IM formulation. For the IM formulation, 39% of olanzapine is released within first 0.5 h with complete release achieved within 24 hours. For TV-44749, only 3% of olanzapine is released within 4 hours and at the end of IVR experiment at 72 hours, only 14% of olanzapine is released."

CNS Disorders • Schizophrenia

Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

SOLARIS: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy and Safety of TV-44749 in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=640 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Psychiatry • Schizophrenia

Evaluation of the pharmacokinetics of TV-44749, newly developed once-monthly extended-release formulation of olanzapine in healthy volunteers and patients with schizophrenia (ECNP 2023) - "Under steady-state conditions, TV-44749 doses 283mg and 566mg provided systemic exposure comparable to those observed after therapeutic doses of daily oral olanzapine administration at steady state. The safety and PK results of this study informed the design of the phase 3 study for TV-44749."

Clinical • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • SS18