Decades-Old Schizophrenia Drug Wins Approval for New Formulation

The FDA approved an easier-to-use once-monthly subcutaneous injectable form of olanzapine (Weltruza) for schizophrenia in adults, Teva Pharmaceuticals announced on Friday.

A decades-old drug, olanzapine in its oral form is the most widely prescribed atypical antipsychotic, but daily treatment can bring adherence issues and some patients prefer less-frequent dosing.

The new long-acting injectable requires no loading doses and no monitoring for post-injection delirium/sedation syndrome (PDSS), an issue that has hampered uptake of other available long-acting olanzapine formulations such as Zyprexa Relprevv, which carries a risk evaluation and mitigation strategy program requiring 3 hours of monitoring for PDSS.

PDSS has been associated with agitation, anxiety, and confusion, with reports including patients who walked into walls or fell asleep in public in the first few hours after treatment.

“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, of the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, in the company’s press release.

“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,” Correll added.

To match the approved oral olanzapine doses (10 mg, 15 mg, and 20 mg), the new long-acting injectable will be available in doses of 318 mg, 425 mg, and 531 mg, respectively.

Approval was supported by the phase III SOLARIS trial. For the primary endpoint, all dose groups surpassed placebo for mean difference in change in the Positive and Negative Syndrome Scale (PANSS) total score, according to a 2024 press release from Teva. From baseline to week 8, differences ranged from -9.71 to -11.27 points (P<0.001 for all comparisons). Other key secondary endpoints — Clinical Global Impressions-schizophrenia and Personal and Social Performance Scale — showed superiority as well, and no PDSS cases occurred.

Like other antipsychotics, the new olanzapine product contains a boxed warning over an increased mortality risk for elderly patients with dementia-related psychosis.

Despite no evidence of PDSS in trials, the labeling for the new olanzapine product still includes PDSS among the warnings and precautions. Other potential risks noted in that section include neuroleptic malignant syndrome; metabolic changes; tardive dyskinesia; orthostatic hypotension; leukopenia, neutropenia, and agranulocytosis; seizures; potential for cognitive and motor impairment; anticholinergic effects; and laboratory abnormalities.

The safety profile in SOLARIS was generally consistent with oral olanzapine, with common adverse events that included increased weight, somnolence, headache, and constipation, along with reactions specific to the injection formulation such as induration, pain, erythema, pruritus, and swelling at the injection site.