Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company dedicated to central nervous system (CNS) therapeutics, has announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA). The application seeks approval for CAPLYTA (lumateperone) as an adjunctive treatment for adults with Major Depressive Disorder (MDD) who have not adequately responded to antidepressant therapy.
Addressing a Critical Need
Major Depressive Disorder is a prevalent and debilitating condition. Despite the availability of treatments, more than half of patients fail to achieve satisfactory relief from symptoms using antidepressants alone. “MDD is a highly prevalent condition with a significant need for efficacious, safe, and well-tolerated medicines,” said Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies. He expressed optimism about CAPLYTA’s potential to become a leading adjunctive treatment, contingent on FDA approval, citing its demonstrated efficacy and safety profile.
Basis for the Application
The sNDA submission is supported by two pivotal Phase 3 studies—Studies 501 and 502. These were double-blind, placebo-controlled trials conducted globally, focusing on adults with a primary diagnosis of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Participants in these studies had shown inadequate responses to ongoing antidepressant therapy, highlighting the unmet need for additional treatment options.
Study Results
In both studies, CAPLYTA, when combined with an antidepressant, demonstrated significant improvements in depressive symptoms compared to placebo. The Montgomery-Åsberg Depression Rating Scale (MADRS), a widely recognized tool for measuring the severity of depression, was used as the primary endpoint.
- Study 501: CAPLYTA showed a 4.9-point improvement over placebo on the MADRS total score, with an effect size of 0.61.
- Study 502: CAPLYTA demonstrated a 4.5-point improvement, with an effect size of 0.56.
These results underline CAPLYTA’s robust efficacy in alleviating depressive symptoms in patients with inadequate responses to antidepressants.
Safety and Tolerability
CAPLYTA’s efficacy is complemented by its favorable safety and tolerability profile, making it a promising candidate for adjunctive MDD treatment.
Key Findings from Safety Data
Pooled safety data from Studies 501 and 502 revealed that CAPLYTA was generally well tolerated.
- Adverse Events: The most frequently reported side effects (≥5% incidence and at least twice the rate of placebo) included dizziness, dry mouth, somnolence/sedation, nausea, and fatigue.
- Metabolic and Weight Profiles: Metabolic changes and weight gain were comparable to placebo, a crucial factor for many MDD patients concerned about medication-related weight gain.
- Movement Disorders: Rates of extrapyramidal symptoms (movement disorders commonly associated with psychiatric medications) were low, further emphasizing CAPLYTA’s tolerability.
The Path Forward
Pending FDA approval, CAPLYTA could address a significant gap in the treatment of Major Depressive Disorder by offering an effective and well-tolerated option for patients who do not fully respond to antidepressants alone. Intra-Cellular Therapies aims to work closely with the FDA during the review process to expedite availability to those in need.
The promising data from the Phase 3 studies, coupled with CAPLYTA’s favorable safety profile, positions the drug as a strong candidate for improving outcomes in MDD treatment. If approved, CAPLYTA could become a valuable addition to the therapeutic arsenal for managing this challenging condition.
With the sNDA now under review, Intra-Cellular Therapies reaffirms its commitment to advancing innovative CNS treatments and addressing the unmet needs of patients with mental health disorders.
