What the Olanzapine Depot Approval Means for CMC Teams

The FDA has approved Teva Pharmaceuticals’ Weltruza (olanzapine) for extended-release injectable suspension, a once-monthly subcutaneous long-acting injectable for the treatment of schizophrenia in adults.¹ The product requires no loading doses, no oral supplementation, and no post-injection monitoring, and it will be available in the US in the coming weeks in 318-mg, 425-mg, and 531-mg strengths. Those doses correspond to daily oral olanzapine doses of 10 mg, 15 mg, and 20 mg, respectively.

Olanzapine is the most widely prescribed atypical antipsychotic for schizophrenia as a daily oral treatment, but adherence to daily dosing remains a persistent barrier to long-term symptom control and contributes to relapse.¹ An estimated 2.1 million people in the US are currently diagnosed with schizophrenia.

“Olanzapine has been a trusted and foundational treatment option for people living with schizophrenia for more than 30 years, but adherence continues to be a major barrier to stability, particularly for those who rely on daily oral medications,” said Christoph Correll, MD, clinical professor of psychiatry, Zucker School of Medicine at Hofstra/Northwell, in a press release.¹ “By offering a subcutaneous long-acting injectable formulation with achievement of therapeutic blood levels without oral cotreatment, loading doses or booster injections, this new treatment option can help empower patients, support their care partners and provide clinicians with an important new tool to assist in managing this complex condition more effectively.”

What Did the SOLARIS Trial Show?

The approval is based on the Phase III SOLARIS trial, a multinational, randomized, double-blind, placebo-controlled study.¹ In the first 8-week period, 675 patients aged 18 to 64 years were randomized 1:1:1:1 to low, medium, or high doses of the olanzapine injectable or placebo. In a subsequent 48-week period, patients who had received placebo were re-randomized to one of the three active doses. The primary endpoint was the Positive and Negative Syndrome Scale; key secondary measures assessed illness severity and personal and social functioning. Teva reported improvement across all three measures.

All three doses were similarly tolerated.¹ The most common adverse events were weight gain, somnolence, headache, constipation, and injection site reactions. Weight gain and metabolic changes, including clinically significant weight gain, were consistent with the known profile of oral olanzapine. Discontinuations due to common adverse events occurred in 5% of patients receiving the active drug vs. 4% receiving placebo.

Why Does This Formulation Matter?

The previously available long-acting olanzapine is administered intramuscularly and is associated with post-injection delirium/sedation syndrome (PDSS), which occurs when too much drug enters the bloodstream too quickly and has required extended observation after each dose.¹ Weltruza’s labeling still describes the PDSS risk observed with the intramuscular product, noting it is not known whether PDSS can occur with the subcutaneous formulation. Removing the monitoring requirement is therefore a release-control achievement as much as a clinical one.

“WELTRUZA combines proven science and novel formulation innovation to eliminate the need for monitoring after each injection, addressing a significant barrier to treatment and advancing care for people living with schizophrenia,” said Eric Hughes, MD, PhD, CMO, Teva, in the press release.¹

Weltruza uses SteadyTeq, a copolymer technology proprietary to Medincell that provides controlled, sustained release of olanzapine.¹ It is the second schizophrenia product approved on the platform, following Uzedy (risperidone), approved in April 2023. A second approval on the same delivery system suggests that polymer depot platforms, once validated, can be extended to additional molecules with established efficacy, potentially shortening development timelines and leveraging existing polymer supply, analytical methods, and sterile manufacturing experience.

Polymer-based depots remain technically demanding.² In situ systems, microspheres, suspensions, and oil-based injections each carry distinct formulation and release-rate challenges. Depot formulations can be tuned to a target release duration and dose, but reaching therapeutic levels from the first injection without a burst large enough to raise safety concerns remains a central development hurdle.

What Does a Study on Controlling Depot Release Show?

Published research from Medincell scientists shows the formulation variables behind solvent-exchange depots, although the study evaluated polycarbonate-based copolymers rather than the polymer technology licensed for Weltruza.³ Once the formulation contacted aqueous buffer, the organic solvent diffused out within about 2 days, and the water-insoluble copolymer precipitated to entrap the drug. Formulations with fully dissolved drug released their cargo almost immediately, whereas suspensions sustained delivery, and higher suspended-drug loads reduced the initial burst. Changing the copolymers’ hydrophilic and hydrophobic block lengths shifted in vitro release from roughly 40 days to more than 240 days. A 28-day rat study confirmed sustained delivery without evident injection-site reactions.

References

1. Teva Pharmaceutical Industries Ltd. Teva announces U.S. Food and Drug Administration (FDA) approval of WELTRUZA (olanzapine) for extended-release injectable suspension, as the first and only once-monthly subcutaneous injectable olanzapine for adults with schizophrenia. News release. October 9, 2026. Accessed October 9, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Announces-U-S--Food-and-Drug-Administration-FDA-Approval-of-WELTRUZA-Olanzapine-For-Extended-Release-Injectable-Suspension-as-the-First-and-Only-Once-Monthly-Subcutaneous-Injectable-Olanzapine-for-Adults-with-Schizophrenia/default.aspx
2. Rhee YS, Park CW, DeLuca PP, Mansour HM. Sustained-release injectable drug delivery. Pharmaceutical Technology. Published November 1, 2010. Accessed October 9, 2026. https://www.pharmtech.com/view/sustained-release-injectable-drug-delivery
3. Cagnon ME, Curia S, Serindoux J, Cros JM, Ng F, Lopez-Noriega A. Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables. Pharmaceutics. 2021;13(5):605. Published 2021 Apr 22. doi:10.3390/pharmaceutics13050605