8-K: Intra-Cellular Therapies Announces Positive Phase 3 Results for Lumateperone in Major Depressive Disorder

Intra-Cellular Therapies reports successful topline results from a Phase 3 trial of lumateperone as an adjunctive treatment for major depressive disorder, paving the way for a supplemental New Drug Application.

Summary

• Intra-Cellular Therapies has announced positive results from Study 502, a Phase 3 trial evaluating lumateperone 42 mg as an add-on therapy to antidepressants for major depressive disorder (MDD).
• The study met its primary endpoint, showing a statistically significant and clinically meaningful reduction in depression symptoms as measured by the Montgomery-sberg Depression Rating Scale (MADRS) at week 6.
• Patients taking lumateperone experienced a 4.5 point greater reduction in MADRS scores compared to those on placebo (p<0.0001, effect size of 0.56).
• The trial also met its key secondary endpoint, demonstrating a significant improvement on the Clinical Global Impression Scale for Severity of Illness (CGI-S) at week 6 (p<0.0001, effect size of 0.51).
• Statistically significant improvements were also observed on the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scale.
• The safety and tolerability of lumateperone were consistent with previous trials, with common side effects including dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue.
• The company plans to submit a supplemental New Drug Application (sNDA) to the FDA in the second half of 2024 based on the results of this study and a previous positive Phase 3 trial (Study 501).

Sentiment

Score: 8

Explanation: The document presents very positive results from a Phase 3 trial, with clear statistical significance and a manageable safety profile. The company is moving forward with regulatory submissions, indicating a strong positive outlook for the drug's future.

Positives

• The study met both its primary and key secondary endpoints with statistically significant results.
• The drug demonstrated a clinically meaningful reduction in depressive symptoms.
• The safety and tolerability profile was consistent with previous trials, suggesting a manageable side effect profile.
• The results from Study 502, combined with Study 501, support the planned sNDA submission for MDD.
• The drug showed improvement in patient-reported outcomes as measured by the QIDS-SR scale.

Negatives

• The most common adverse events (5% and greater than twice placebo) were dizziness, somnolence, dry mouth, nausea, diarrhea and fatigue.
• Adverse events were mostly mild to moderate and resolved within the course of the study.

Risks

• There are no guarantees that CAPLYTA will be commercially successful.
• The company may encounter issues, delays or other challenges in commercializing CAPLYTA.
• CAPLYTA may not receive adequate reimbursement from third-party payors.
• The degree to which CAPLYTA receives acceptance from patients and physicians for its approved indications is uncertain.
• There are challenges associated with execution of sales activities.
• Results achieved in CAPLYTA in the treatment of schizophrenia and bipolar depression following commercial launch of the product may be different than observed in clinical trials, and may vary among patients.
• There are challenges associated with supply and manufacturing activities.
• The company may encounter unexpected safety or tolerability issues with CAPLYTA following commercial launch for the treatment of schizophrenia or bipolar depression or in ongoing or future trials and other development activities.
• There is no guarantee that a generic equivalent of CAPLYTA will not be approved and enter the market before the expiration of our patents.
• There is no guarantee that the planned sNDA for the treatment of MDD will be submitted or approved, if at all, on the timeline that is expected.
• Other product candidates may not be successful or may take longer and be more costly than anticipated.
• Product candidates that appeared promising in earlier research and clinical trials may not demonstrate safety and/or efficacy in larger-scale or later clinical trials or in clinical trials for other indications.
• The company's proposals with respect to the regulatory path for product candidates may not be acceptable to the FDA.
• The company relies on collaborative partners and other third parties for development of product candidates.
• Impacts on the business, including on the commercialization of CAPLYTA and clinical trials, as a result of the COVID-19 pandemic, the conflicts in Ukraine and the Middle East, global economic uncertainty, inflation, higher interest rates or market disruptions.

Future Outlook

The company anticipates submitting a supplemental New Drug Application (sNDA) to the FDA in the second half of 2024 for lumateperone as an adjunctive treatment for major depressive disorder.

Management Comments

• Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies, stated that the efficacy results from Studies 501 and 502, along with the favorable safety and tolerability profiles, will make lumateperone a drug of choice for patients with MDD who have an inadequate response to antidepressant therapy.
• Dr. Suresh Durgam, Executive Vice President, Chief Medical Officer of Intra-Cellular Therapies, noted that lumateperone demonstrated a robust effect as an adjunctive treatment to antidepressants in patients with MDD who had inadequate response to antidepressant therapy.

Industry Context

This announcement is significant as it addresses the unmet need for effective treatments for MDD, where a large proportion of patients do not achieve remission with first-line therapies. The positive results position lumateperone as a potential competitor in the market for adjunctive treatments for MDD.

Comparison to Industry Standards

• The effect size of 0.56 on the MADRS scale is considered clinically meaningful and is comparable to other successful adjunctive treatments for MDD.
• The consistent efficacy and safety profile across two Phase 3 trials (Study 501 and 502) strengthens the case for lumateperone's potential approval.
• The reported adverse events are generally consistent with other antipsychotic medications, but the company highlights that they were mostly mild to moderate and resolved within the course of the study.
• Companies like Alkermes (ALKS) with their drug Aristada, and Otsuka Pharmaceutical (OTSKY) with Abilify Maintena, also target the treatment of psychiatric disorders, and the results of this study position Intra-Cellular Therapies as a potential competitor in this space.

Stakeholder Impact

• Shareholders are likely to react positively to the successful trial results and the planned sNDA submission.
• Patients with MDD may benefit from a new treatment option if lumateperone is approved.
• Physicians may have a new tool to treat patients with MDD who have an inadequate response to antidepressant therapy.

Next Steps

• The company plans to submit a supplemental New Drug Application (sNDA) to the FDA in the second half of 2024.
• The company will host a conference call to discuss the results of Study 502.

Key Dates

Keywords

lumateperone, major depressive disorder, MDD, adjunctive therapy, antidepressants, clinical trial, Phase 3, sNDA, CAPLYTA, psychiatric disorders