Long acting olanzapine may improve symptoms in schizophrenia patients: Study

Once-monthly subcutaneous injection of olanzapine (TEV-'749) may improve symptoms in patients with schizophrenia without post injection delirium syndrome (PDSS), according to a new study.

Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd , 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 utilizes SteadyTeq™, a copolymer technology proprietary to Medincell that provides a controlled steady release of olanzapine, the most prescribed 2nd generation antipsychotic for schizophrenia in the U.S.

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. Key secondary endpoints of CGI-S (Clinical Global Impressions – schizophrenia) and PSP (Personal and Social Performance Scale) total score were also statistically significant after adjusting for multiplicity. No cases of PDSS have been reported to date, after administration of approximately 80% of the target injection number.

An estimated 3.5 million people are currently diagnosed with schizophrenia in the U.S. It is a chronic, progressive, and severely debilitating mental disorder that affects how one thinks, feels and behaves. Currently, there is no long-acting olanzapine treatment option available for schizophrenia that does not risk post-injection delirium/sedation syndrome (PDSS). PDSS is characterized by the sudden and unexpected onset of delirium or sedation within the first several hours of receiving treatment and has been associated with the intramuscular injection of long-acting olanzapine.

“These encouraging results from the efficacy portion of our Phase 3 SOLARIS trial demonstrate the potential of TEV-‘749 to be an effective long-acting treatment option for schizophrenia and further show our dedication to advancing innovative science in mental health and beyond,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Schizophrenia can be a devastating disease for both the people struggling with it as well their families. Schizophrenia is often a chronic life-long disease, but by using medication consistently, people can find the treatment help they deserve. This also has the potential to reduce the burden for not only themselves, but their caregivers and loved ones as well.”

The PANSS is composed of 3 subscales: Positive Scale, Negative Scale, and General Psychopathology Scale. Each subscale is rated with 1 to 7 points ranging from absent to extreme. Each of the 30 items is accompanied by a specific definition as well as detailed anchoring criteria for all seven rating points. These seven points represent increasing levels of psychopathology, as follows: 1- absent 2- minimal 3- mild 4- moderate 5- moderate severe 6- severe 7- extreme; the PANSS overall total score ranges from 30 to 210, with a higher score indicating greater symptom severity. The primary efficacy endpoint was measured by change from baseline to week 8 against the PANSS total score.

“These data reinforce the potential of TEV-‘749 as a subcutaneous long-acting injectable by using a proven molecule with an established long-acting delivery system,” said Christoph Correll, MD, Professor of Psychiatry at the Zucker School of Medicine, Hempstead, NY and SOLARIS study co-ordinating investigator. “Most patients with schizophrenia will experience one or more relapses throughout their treatment journeys, so I very much welcome the development of new and innovative long-acting treatment options that may better fit into their lives.”

“The positive news from the phase III SOLARIS trial continues to encourage ongoing innovation in treatment options for those living with schizophrenia. We are thrilled to be part of this journey with Teva through a strong partnership that allows us to leverage our pioneering long-acting technology for the benefit of patients,” said Christophe Douat, CEO of Medincell.

Additional efficacy and safety findings from the Phase 3 SOLARIS study are planned for presentation at a medical meeting later this year.

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 second half of 2024.

TEV-‘749 is an investigational once-monthly subcutaneous long-acting injection of the 2nd 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.  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.