TEV-‘749 Demonstrates No Incidence Of Postinjection Delirium/Sedation Syndrome in New Data

Raymond Orton/AdobeStock

Teva Pharmaceuticals recently shared new positive efficacy, safety, and tolerability results from the phase 3 subcutaneous olanzapine extended-release injection study (SOLARIS) trial evaluating TEV-‘749 in adult patients diagnosed with schizophrenia at the 37th Annual European College of Neuropsychopharmacology Congress in Milan.¹

TEV-‘749 is an investigational once-monthly subcutaneous long-acting injectable (LAI) that steadily releases olanzapine—the most prescribed second generation antipsychotic for schizophrenia in the US—via SteadyTeq, which is a copolymer technology proprietary to Medincell.²

TEV-‘749 met the primary study endpoint, demonstrating significant improvements in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8. Additionally, it met 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 with placebo at week 8. Notably, the SOLARIS (period 1) and phase 1 safety results of TEV-‘749 demonstrated no incidence of postinjection delirium/sedation syndrome (PDSS), or the sudden and unexpected onset of delirium or sedation when medication is released too quickly into the blood after receiving an intramuscular injection. Currently, the only long-acting olanzapine treatment option for schizophrenia carries a risk for PDSS.

“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 health care 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.”

SOLARIS study period 1 is an 8-week, randomized, double-blind, placebo-controlled trial in participants aged 18 to 64 years 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 3 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 vs 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). TEV-‘749 also significantly improved CGI-S scale scores across all 3 dosing groups, with reductions of -0.47 points (high), -0.61 points (medium), and -0.53 points (low) vs placebo from baseline to week 8 (all P<0.0001). Lastly, TEV-‘749 significantly improved PSP scale scores across all 3 dosing groups, with increases of 4.93 points (high), 3.15 points (medium), and 4.63 points (low) vs placebo from baseline to week 8 (all P<0.02).¹

“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 health care providers who rely on olanzapine and also have needs or preferences that require a long-acting option.”

The systemic safety profile of TEV-‘749 was consistent with other approved formulations of olanzapine. Additional safety and tolerability results from period 1, which had 917 active injections, through week 8 of the SOLARIS study show that there were no reported cases of PDSS. Treatment-emergent adverse events that occurred more often in patients receiving TEV-‘749 than placebo included weight increase (35% vs 8%), injection site induration (13% vs 2%), injection site pain (10% vs 4%), and injection site erythema (10% vs 1%). Serious adverse events and discontinuations due to adverse events were reported in 1% and 3% of patients treated with TEV-‘749, respectively, and in 2% and 3% of patients treated with placebo, respectively.

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 expected early in 2025.

References

1. 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. Teva. September 21, 2024. Accessed September 24, 2024. https://www.tevausa.com/news-and-media/press-releases/teva-presents-new-phase-3-efficacy-safety-and-tolerability-data-from-solaris-trial-evaluating-tev-749-/

2. Kuntz L. Phase 3 SOLARIS trial demonstrates potential of TEV-‘749 in schizophrenia. Psychiatric Times. May 9, 2024. https://www.psychiatrictimes.com/view/phase-3-solaris-trial-demonstrates-potential-of-tev-749-in-schizophrenia