FDA approves Weltruza, first once-monthly subcutaneous olanzapine injection for schizophrenia

Adults with schizophrenia will soon have a long-acting form of olanzapine that can be injected subcutaneously once a month and does not require the post-injection observation period tied to the existing intramuscular version, Teva Pharmaceuticals announced in an FDA approval news release.

Weltruza (olanzapine), the extended-release injectable suspension, will be available in three strengths: 318 mg, 425 mg and 531 mg, which correspond to oral olanzapine doses of 10 mg, 15 mg and 20 mg daily, according to the news release published on Oct. 9. Treatment does not require loading doses or oral supplementation at initiation. Teva said it expects the product to be available in the United States in the coming weeks.

The formulation uses SteadyTeq, a copolymer technology owned by Teva partner Medincell that provides controlled, sustained release of olanzapine.

Why post-injection monitoring matters for olanzapine injectables

Zyprexa Relprevv is another long-acting injectable for the treatment of schizophrenia in adults. The intramuscular olanzapine pamoate injection, given every two or four weeks, carries a boxed warning for post-injection delirium/sedation syndrome (PDSS). Under its Risk Evaluation and Mitigation Strategy, the drug may be given only at certified facilities able to observe patients for at least three hours, and patients must be accompanied to their destination afterward, according to the product’s prescribing information. The FDA describes the PDSS risk as present with every injection but less than 1%.

The safety information for Weltruza, which is a subcutaneous long-acting injectable, notes that PDSS has occurred with another extended-release olanzapine product given intramuscularly and that it is unknown whether it can occur with the subcutaneous formulation. The SOLARIS safety analysis found no PDSS events through 56 weeks.

“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,” Eric Hughes, M.D., Ph.D., executive vice president of global R&D and chief medical officer at Teva, said in the news release.

What the SOLARIS trial found

SOLARIS was a randomized, double-blind, placebo-controlled study that enrolled 675 patients with schizophrenia. Weltruza improved symptoms as measured by the Positive and Negative Syndrome Scale, reduced illness severity on the Clinical Global Impression-Severity scale and improved scores on the Personal and Social Performance Scale, according to Teva.

All three doses were similarly tolerated. The most common side effects included increased weight (36%), injection site reactions (12%) and somnolence (7%). Weight gain and metabolic changes, including clinically significant, average weight gain of approximately 12 lbs., were consistent with the systemic safety profile of oral olanzapine.

Adherence and the case for long-acting injectables in schizophrenia

Olanzapine is the most widely prescribed atypical antipsychotic for schizophrenia, but daily oral dosing can make it difficult to sustain symptom improvement and raises the risk of relapse, Teva noted. An estimated 2.1 million people in the United States are diagnosed with schizophrenia.

The discontinuation rate for oral antipsychotics in schizophrenia ranges from 26% to 44%, and up to two-thirds of patients are at least partially nonadherent, increasing the risk of hospitalization, according to a review published in Patient Preference and Adherence.

Weltruza is the second FDA-approved product from the Teva and Medincell collaboration, following Uzedy (risperidone), a subcutaneous long-acting injectable approved in 2023.

The current list price of Weltruza is $3,950, according to an investor call held on Oct. 9.

“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,” Christoph Correll, M.D., clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, said in the news release.