Lumateperone for MDD Update: J&J Acquires Intra-Cellular as FDA sNDA Decision Approaches

Johnson & Johnson announced on January 13, 2025, acquisition of Intra-Cellular Therapies, Inc. gaining the once-daily oral therapy lumateperone, currently awaiting determination from the US Food and Drug Administration for use as an adjunctive therapy for Major Depressive Disorder (MDD), according to a Intra-Cellular news release.1

The acquisition also gives J&J the clinical-stage agent ITI-1284, under investigation for treatment of generalized anxiety disorder (GAD) and agitation associated with Alzheimer’s disease,

Lumateperone, marketed as Caplyta, is already FDA approved for the treatment of schizophrenia in adults and for depressive episodes in bipolar I or II disorder, either as monotherapy or in combination with lithium or valproate.

In December 2024, Intra-Cellular Therapies submitted a supplemental new drug application for lumateperone to be used as an adjunctive therapy for MDD, aiming to fill an unmet need in a disorder that affects an estimated 21 million adults in the United States.

The sNDA submission was based on positive findings from two phase 3 global, double-blind, placebo-controlled trials in people with a primary diagnosis of MDD, as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, who have had an inadequate response to antidepressants. Data from studies 501 and 502 showed that lumateperone, when added to antidepressant treatment, demonstrated robust efficacy for MDD in the primary endpoint, the Montgomery Asberg Depression Rating Scale (MADRS) total score, with a large separation compared to placebo of 4.9 points (effect size 0.61) in study 501 and 4.5 points (effect size 0.56) vs placebo in study 502.2

In addition, lumateperone also demonstrated a favorable safety and tolerability profile, including a favorable metabolic, weight, and movement disorder profile. In the pooled safety data for both trials, the most commonly reported adverse events that were observed at a rate greater than or equal to 5% for lumateperone and greater than twice the rate of placebo were dizziness, dry mouth, somnolence/sedation, nausea, and fatigue. Metabolic and weight changes were similar to placebo and the rates of extrapyramidal symptoms were low, according to the press release.2

“Caplyta has robust efficacy, proven safety and favorable tolerability across all three approved indications, without the need for dose titration frequently associated with this class of therapies,” said John Reed, M.D., Ph.D., Executive Vice President, R&D, Innovative Medicine, Johnson & Johnson, in the news release. “With positive Phase 3 data in MDD as an adjunctive therapy and additional Phase 3 trials in other mental health disorders underway, we believe Caplyta has the potential to become a new standard of care for the treatment of some of today’s most prevalent and debilitating mental health disorders.”

An estimated 21 million adults live with MDD, one of the most common psychiatric disorders and a leading cause of disability, according to the news release.1

The acquisition also brings ITI-1284 into J&J’s fold, a Phase 2 compound under investigation for treatment of GAD and Alzheimer’s disease-related psychosis and agitation. About 6.8 million adults live with GAD, a mental and behavioral disorder that causes excessive and uncontrollable worry and fear. Approximately 6 million adults live with Alzheimer’s disease, a neurodegenerative brain disorder that causes progressive memory loss and a decline in cognitive abilities severe enough to significantly interfere with daily life.1

References

1. Johnson & Johnson Strengthens Neuroscience Leadership with Acquisition of Intra-Cellular Therapies, Inc. Published January 13, 2025. Accessed January 13, 2025.
   https://ir.intracellulartherapies.com/news-releases/news-release-details/johnson-johnson-strengthens-neuroscience-leadership-acquisition.
2. FDA review sought for lumateperone as adjunctive therapy for major depressive disorder. PatientCareOnline website. Published December 12, 2024. Accessed January 13, 2025. https://www.patientcareonline.com/view/fda-review-sought-for-lumateperone-as-adjunctive-therapy-for-major-depressive-disorder.