The U.S. Food and Drug Administration (FDA) has approved WELTRUZA™ (olanzapine) for extended-release injectable suspension for the treatment of schizophrenia in adults. WELTRUZA is the first and only once-monthly subcutaneous long-acting injectable (LAI) formulation of olanzapine and requires no loading doses, no oral supplementation, and no post-injection monitoring.
Olanzapine is the most widely prescribed atypical antipsychotic for schizophrenia as a daily oral treatment, but daily dosing can make it difficult to sustain long-term symptom improvement because of adherence challenges, which increase the risk of instability and relapse. WELTRUZA was developed to provide the established efficacy of olanzapine in a once-monthly formulation.
Dosing
- Once-monthly subcutaneous injection in three strengths: 318 mg, 425 mg, and 531 mg
- These strengths correspond to the approved daily oral olanzapine doses of 10 mg, 15 mg, and 20 mg, respectively
- No loading doses, oral supplementation, or post-injection monitoring required
Evidence supporting approval
The approval is based on the pivotal Phase 3 SOLARIS trial. In the first 8-week period, 675 adults aged 18 to 64 years with schizophrenia were randomized 1:1:1:1 in a multinational, double-blind, placebo-controlled design to once-monthly WELTRUZA (low, medium, or high dose) or placebo. In the following 48-week period, participants who completed period one on placebo were re-randomized equally to one of the three WELTRUZA doses, and those who completed period one on active treatment remained on their established dose.
The primary objective was efficacy as measured by the Positive and Negative Syndrome Scale (PANSS), with Clinical Global Impressions–Severity (CGI-S) and Personal and Social Performance (PSP) as key secondary measures. Results showed that olanzapine extended release improved symptoms (PANSS), significantly reduced illness severity (CGI-S), and improved personal and social functioning (PSP). Effect sizes were not included in the company announcement.
Safety and tolerability
- All three doses were similarly tolerated in SOLARIS. The most common adverse events were increased weight, somnolence, headache, constipation, and injection site reactions.
- Weight gain and metabolic changes were observed and were consistent with the systemic safety profile of oral olanzapine, including clinically significant weight gain.
- Discontinuations due to common adverse events were 5% with WELTRUZA and 4% with placebo.
- Boxed warning: increased risk of death in elderly patients with dementia-related psychosis. WELTRUZA is not approved for this population.
- Post-injection delirium/sedation syndrome (PDSS) has been reported with another extended-release intramuscular olanzapine injection. It is not known whether PDSS can occur with subcutaneous WELTRUZA.
- Other warnings include neuroleptic malignant syndrome, DRESS, hyperglycemia and dyslipidemia, tardive dyskinesia, orthostatic hypotension, falls, leukopenia, dysphagia, seizures, hyperprolactinemia, and anticholinergic effects.
Please refer to the full Prescribing Information, including the Boxed Warning and Medication Guide, for complete safety information.
