Lumateperone Tosylate

A major depressive disorder nod grows Caplyta’s total patient reach to more than 30 million people in the U.S. Johnson & Johnson’s decision to splash out $14.6 billion on its purchase of Intra-Cellular Therapies earlier this year was largely driven by the acquired company's rising antipsychotic star Caplyta and the drug's potential to expand into the massive treatment market for major depressive disorder (MDD).Now, with that coveted approval in hand, the drug is poised to reach many more patients and potentially live up to its blockbuster potential.Already a dominant force in its approved schizophrenia and bipolar depression indications, Caplyta’s FDA label now also includes its use as an adjunctive therapy to antidepressants in U.S. adults with MDD, Johnson & Johnson announced in a Thursday press release.Between the three indications on Caplyta's new label, the biggest by far is MDD, which impacts about 21 million adults each year, according to J&J. Two-thirds of patients with depression fail to achieve remission with first-line treatment, which is where Caplyta will now step in.As an add-on therapy, the drug can help patients “retain the benefit they are receiving from their current antidepressant, while building on it to achieve greater symptom relief,” Intra-Cellular Chief Medical Officer Suresh Durgam, M.D., explained in an emailed statement.In studies, Caplyta paired with an oral antidepressant demonstrated statistically significant and clinically meaningful improvements in depression symptoms compared to an antidepressant plus placebo.In one of two pivotal trials, Study 502, patients who had an inadequate response to ongoing antidepressant therapy experienced a 4.5-point reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) on the Caplyta regimen compared to the placebo group at Week 6. Similar results were observed in Study 501, which saw an average 4.9-point reduction for Caplyta compared to placebo at Week 6 on the same scale.In addition, a six-month open-label extension study showed that 80% of MDD patients who took Caplyta achieved a response and, crucially, 65% reached remission from depression.  Caplyta, with $680 million in 2024 sales, has been a commercial and clinical success since its 2019 approval, but MDD represents a much larger market opportunity. At least triple the size of the bipolar space, analysts say, the MDD field is teeming with competition from treatment agents new and old.J&J is anticipating Caplyta will eventually bring in $5 billion in annual sales, CEO Joaquin Duato noted on the company’s recent quarterly earnings call (PDF) with investors. When the company first added the drug to its “industry-leading” neuropsychiatry lineup, the buyout was expected to further solidify sales growth “above analyst expectations now through the remainder of the decade,” J&J said at the time.In recent years, J&J itself has played a key role in moving the MDD market beyond standard selective serotonin reuptake inhibitors with its ketamine-based nasal spray Spravato. Initially approved as a late-line add-on to oral antidepressants, the FDA in January signed off on the N-methyl D-asparate (NMDA) receptor antagonist’s use as a monotherapy for adult patients with MDD who've had an inadequate response to at least two oral antidepressants.At the time of Spravato's first FDA approval in 2019, J&J touted the drug as offering the "first new mechanism of action in decades to treat major depressive disorder." In 2022, Axsome brought its own fast-acting oral NMDA drug to market with Auvelity, while Fabre-Kramer Pharmaceuticals rolled out a first-in-class serotonin-targeting antidepressant called Exxua the following year. AbbVie, too, has an innovative offering on the depression market with Vraylar.Beyond its new approval in depression, Caplyta can be used as a monotherapy or paired with standard lithium or valproate to treat depressive episodes linked to bipolar 1 or bipolar 2 disorder. While the drug already has a wide schizophrenia label, J&J is looking to expand its benefits in the disorder with a potential label expansion that would allow Caplyta to prevent relapses in schizophrenia. 

Johnson & Johnson’s Caplyta has won FDA approval as a new adjunctive treatment for patients with major depressive disorder, bolstering the acquisition that gave the large pharma control of the drug. The new approval is Caplyta’s first foray into the depression market after its original approval as an antipsychotic for schizophrenia, and for depressive symptoms associated with bipolar I and II. The decision was based on two Phase 3 studies that found that a once-daily oral dose of Caplyta, when tacked onto an antidepressant, spurred a statistically significant improvement in depression symptoms. Caplyta was the foundation of J&J’s $14.6 billion acquisition of Intra-Cellular Therapies earlier this year, which followed Phase 3 readouts in major depressive disorder in 2024. J&J is looking to win a slice of the depression market, specifically the more than half of patients whose first-line treatments don’t help enough because of weak efficacy or side effects. Suresh Durgam, chief medical officer of the Intra-Cellular unit, said the goal is for patients to reach remission, meaning a score lower than 10 on the Montgomery-Åsberg Depression Rating Scale. “We want to make sure that patients are symptom-free,” Durgam said in an interview with Endpoints News ahead of the announcement. In the trials, the clinical improvements were often felt quickly. In one test, Caplyta-treated patients had a statistically significant improvement in symptoms after a week of treatment. In the other trial, the results hit that mark by week two. In practice, that means that patients should be able to know within a week or two whether or not the drug is working, Durgam said. With other antidepressants, it can take weeks or months to properly assess efficacy. The most common side effects included dry mouth, dizziness and sleepiness. At least 5% of patients reported tremors in one of the two Phase 3 trials as well. Durgam said that most of those symptoms dissipated on their own after the first two weeks of treatment. He noted that adding on Caplyta didn’t come with worsening metabolic measures, including glucose and cholesterol levels. J&J is continuing to study the use of Caplyta for a number of similar psychiatric conditions in children, even as federal health officials have questioned the use of antidepressants in children . “If you have something that is less likely to cause liability, that would generally be useful in children too,” Durgam said. “We would generally expect that the profile will be similar.”