FDA Approves Weltruza, a Once-Monthly Olanzapine Injection

The Food and Drug Administration has approved Weltruza, a once-monthly subcutaneous injection of olanzapine for adults with schizophrenia — the first long-acting injectable form of one of psychiatry's most prescribed antipsychotics that requires no loading doses, no oral supplementation and no monitoring period after each injection. Teva Pharmaceuticals announced the approval Friday and said the product will reach the U.S. market in three strengths in the coming weeks.

What the formulation changes

Olanzapine has been a standard treatment for schizophrenia for more than three decades, but almost always as a daily pill. The risk with daily oral antipsychotics is not efficacy — it is adherence, and its failure mode is relapse. An existing intramuscular long-acting injection of olanzapine carries a Risk Evaluation and Mitigation Strategy that requires administration in a certified health care facility and three hours of observation afterward, a requirement driven by the rare risk of post-injection delirium/sedation syndrome (PDSS). The subcutaneous version, developed using a copolymer release technology licensed from the French company Medincell, eliminates the loading dose, the oral overlap and the observation window.

One caveat travels with the approval: no cases of PDSS were observed or confirmed across 3,971 injections in the pivotal trial, but the labeling still carries a PDSS warning, noting that the syndrome has occurred with the intramuscular formulation and that its occurrence with subcutaneous dosing is unknown. The label also includes the boxed warning for increased mortality in elderly patients with dementia-related psychosis.

Inside the SOLARIS trial

The approval rests on SOLARIS, a multinational, randomized, double-blind, placebo-controlled Phase 3 study in patients aged 18 to 64 with schizophrenia. In the first eight-week period, 675 patients were randomized 1:1:1:1 to a low, medium or high dose of olanzapine long-acting injectable or placebo, given once monthly by subcutaneous injection. In the 48-week second period, patients who completed placebo were rerandomized across the three active doses.

The primary endpoint was change in Positive and Negative Syndrome Scale total score, with illness severity and personal and social functioning as key secondary measures. Teva reported improvement on all three. All three doses were similarly tolerated, and 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 systemic profile of oral olanzapine. Discontinuations because of common adverse events occurred in 5 percent of treated patients and 4 percent of those on placebo. In post hoc analyses, more than half of participants reached clinical stabilization, and more than 20 percent of those treated for six months or longer met remission criteria.

The dose correspondence

Weltruza will be sold in single monthly subcutaneous doses of 318 mg, 425 mg and 531 mg, which correspond to oral olanzapine doses of 10 mg, 15 mg and 20 mg respectively. Teva said the product will be available in the U.S. in the coming weeks; a European marketing authorization application was accepted by the European Medicines Agency in May and the drug is not yet approved in Europe. An estimated 2.1 million people in the United States are diagnosed with schizophrenia.

Adherence is the whole point

"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," Christoph Correll, a clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, said in Teva's announcement. "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."

The logic will be familiar to anyone who works in addiction medicine: the same reasoning drove the shift toward injectable buprenorphine and extended-release naltrexone, where a monthly or weekly dose removes the daily decision that becomes the first thing to collapse when someone destabilizes. Substance use frequently co-occurs with schizophrenia, and dual diagnosis care depends on patients staying in contact with treatment long enough for anything else to work.

What is still unknown

Teva has not announced pricing, and the commercial question is whether insurers will place a long-acting injectable on formulary when generic oral olanzapine costs a few dollars a month. The company's chief medical officer, Eric Hughes, framed the approval as a formulation advance — "eliminating the need for monitoring after each injection, addressing a significant barrier to treatment" — rather than a new mechanism of action. Olanzapine's metabolic profile, the reason many clinicians reach for other antipsychotics first, is unchanged by the delivery route. For patients who cycle in and out of treatment or hospital care, the practical test will be whether a monthly injection keeps them stable enough to stay engaged, which is precisely what the label cannot promise.