FDA Approves Once-Monthly Subcutaneous Olanzapine (Weltruza) for Schizophrenia
Teva said Oct. 9 that FDA approved Weltruza, a once-monthly subcutaneous olanzapine for adults with schizophrenia, with no post-injection monitoring required. All three doses beat placebo at week 8 in SOLARIS, but whether PDSS can occur with it is not known.
On Oct. 9, Teva Pharmaceuticals announced that the Food and Drug Administration had approved olanzapine for extended-release injectable suspension (Weltruza), a once-monthly subcutaneous long-acting injection for adults with schizophrenia. Teva calls it the first and only once-monthly subcutaneous olanzapine and says it will be available in the United States in the coming weeks.
Long-acting olanzapine has until now meant the intramuscular product, which Psychiatric Times noted carries a Risk Evaluation and Mitigation Strategy requiring administration in a certified health care facility and three hours of monitoring after each injection.
What was approved
Weltruza comes in 318 mg, 425 mg and 531 mg strengths, which Teva says correspond to oral olanzapine 10 mg, 15 mg and 20 mg daily. Teva says it requires no loading doses, no oral supplementation and no post-injection monitoring. The full prescribing information was not yet posted on FDA or DailyMed as of Oct. 12, so the administration section should be read once it is.
What SOLARIS showed
The approval rests on the phase 3 SOLARIS trial. Period one was an eight-week, randomized, double-blind, placebo-controlled study of 675 adults aged 18 to 64, randomized 1:1:1:1 to 318 mg (n=169), 425 mg (n=169), 531 mg (n=169) or placebo (n=168) once monthly, according to Teva.
The primary endpoint was change in Positive and Negative Syndrome Scale total score at week 8. Teva and Medincell reported placebo-adjusted differences of -9.71 points for the high dose, -11.27 for the medium dose and -9.71 for the low dose, with adjusted P values below 0.001 for each. Clinical Global Impressions-Severity and Personal and Social Performance scores were also significant after multiplicity adjustment. Confidence intervals have not been released, and we found no peer-reviewed SOLARIS publication.
The placebo-controlled data run eight weeks. What is known about PDSS, weight and longer-term effect comes from open-label follow-up with no active comparator.
Safety
Period two was an open-label extension of up to 48 weeks. Across the trial, Teva reported that 74 percent of participants had a treatment-emergent adverse event and 8 percent discontinued because of one. Weight increase was the most common event, at 36 percent, followed by injection-site induration and pain (12 percent each), injection-site erythema (10 percent) and somnolence (7 percent). Among 137 participants treated for at least 48 weeks, mean weight gain was 5.6 kg.
Teva reported no suspected or confirmed post-injection delirium/sedation syndrome across 3,470 injections. Its safety information still says PDSS has occurred with the intramuscular product and that it is not known whether it can occur with Weltruza. With the intramuscular product, PDSS followed about 0.07 percent of injections; by a rule-of-three estimate (our arithmetic), zero events in 3,470 injections cannot exclude a rate of that size.
The boxed warning is the class warning on increased mortality in elderly patients with dementia-related psychosis. Teva's safety information also lists stroke in elderly patients, neuroleptic malignant syndrome, DRESS, metabolic changes, tardive dyskinesia, orthostatic hypotension, falls, low white blood cell counts, dysphagia, seizures and hyperprolactinemia.
What it means in clinic
SOLARIS compared Weltruza with placebo, not with oral or intramuscular olanzapine, and enrolled adults up to 64. For practices that avoided long-acting olanzapine because of the observation requirement, the label's administration section is the thing to read before changing workflow. Olanzapine's metabolic burden is unchanged, so baseline and follow-up weight, glucose and lipid monitoring still apply. Teva has not announced a price; ask payers about coverage and prior authorization before the first patient is scheduled.
Reported, fact-checked and edited by The Script Pad's editorial staff.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
