Teva Pharmaceuticals announced positive topline results from the Phase 3 SOLARIS trial evaluating TEV-749 (olanzapine) as a once-monthly subcutaneous long-acting injectable for treating schizophrenia in adults. The study, presented at the 37th Annual European College of Neuropsychopharmacology (ECNP) Congress, demonstrated significant efficacy and a favorable safety profile, notably with no reported cases of post-injection delirium/sedation syndrome (PDSS).
Efficacy of TEV-749 in Schizophrenia
The Phase 3 SOLARIS trial was a multinational, multicenter, randomized, double-blind, placebo-controlled study involving 675 patients aged 18-65 years diagnosed with schizophrenia. Participants were administered TEV-749 via subcutaneous injection once monthly at low (318 mg), medium (425 mg), or high (531 mg) doses, corresponding to 10 mg, 15 mg, and 20 mg daily oral olanzapine, respectively, or placebo in a 1:1:1:1 ratio. The primary endpoint was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8.
The study met its primary endpoint, with TEV-749 demonstrating statistically significant mean differences in the change in PANSS total scores from baseline to week 8 compared to placebo across all three dosing groups (p<0.0001). Key secondary endpoints also showed significant improvements:
- Clinical Global Impression-Severity (CGI-S) scale scores improved significantly across all three dosing groups (p<0.0001).
- Personal and Social Performance (PSP) scale scores also showed significant improvement across all three dosing groups (p<0.02).
Safety and Tolerability
A critical finding of the SOLARIS trial and a Phase 1 study was the absence of post-injection delirium/sedation syndrome (PDSS) in participants treated with TEV-749 to date. This is particularly important as current long-acting olanzapine treatments carry a boxed warning for PDSS, which can limit their use. The overall safety profile of TEV-749 was consistent with other approved formulations of olanzapine.
Treatment-emergent adverse events that occurred more often in patients receiving TEV-749 versus 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.
Expert Commentary
"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."
Future Directions
The long-term safety of TEV-749 and the incidence of PDSS are being further evaluated in the SOLARIS open-label study (Period 2), with topline safety data expected in the first half of 2025. TEV-749 utilizes SteadyTeq™, a copolymer technology proprietary to Medincell, designed for controlled and steady release of olanzapine.
TEV-749 is an investigational once-monthly subcutaneous LAI 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.
Schizophrenia Landscape
Schizophrenia is a chronic and debilitating mental disorder affecting approximately 1% of the world's population. It requires continuous management, often involving switching between oral and long-acting injectable (LAI) treatments. The availability of a long-acting olanzapine option without the risk of PDSS could significantly improve treatment adherence and patient outcomes.
