8-K: Intra-Cellular Therapies Submits sNDA to FDA for CAPLYTA in Major Depressive Disorder

Intra-Cellular Therapies has submitted a supplemental New Drug Application to the FDA for CAPLYTA as an adjunctive therapy for major depressive disorder.

Summary

• Intra-Cellular Therapies has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for CAPLYTA (lumateperone) to treat major depressive disorder (MDD) as an add-on therapy to antidepressants.
• The sNDA is based on positive results from two Phase 3 studies, 501 and 502, which showed that CAPLYTA, when added to an antidepressant, demonstrated a significant improvement in depression symptoms compared to placebo.
• Study 501 showed a 4.9 point separation from placebo on the Montgomery Asberg Depression Rating Scale (MADRS) with an effect size of 0.61, while Study 502 showed a 4.5 point separation with an effect size of 0.56.
• CAPLYTA also demonstrated a favorable safety and tolerability profile, with metabolic and weight changes similar to placebo and low rates of extrapyramidal symptoms.
• The most common adverse events reported 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.
• Major Depressive Disorder affects an estimated 21 million adults in the U.S. each year, and approximately two-thirds of patients do not achieve remission with first-line treatment.

Sentiment

Score: 8

Explanation: The document is positive due to the submission of the sNDA and the positive clinical trial results. The potential for CAPLYTA to address a significant unmet need in MDD is also a positive factor. However, there are risks associated with regulatory approval and commercialization, which temper the sentiment slightly.

Positives

• The submission of the sNDA to the FDA is a positive step towards expanding the use of CAPLYTA.
• The Phase 3 studies showed statistically significant and clinically meaningful improvements in depression symptoms when CAPLYTA was added to an antidepressant.
• CAPLYTA demonstrated a favorable safety and tolerability profile, which is important for long-term treatment.
• The drug has the potential to address a significant unmet need in the treatment of MDD, where many patients do not respond adequately to first-line treatments.

Negatives

• The most common adverse events reported were dizziness, dry mouth, somnolence/sedation, nausea, and fatigue, which could impact patient compliance.
• There are boxed warnings regarding increased risk of death in elderly patients with dementia-related psychosis and increased risk of suicidal thoughts and behaviors in pediatric and young adults.
• The drug has contraindications for patients with known hypersensitivity to lumateperone or any components of CAPLYTA.

Risks

• There is no guarantee that the FDA will approve the sNDA for CAPLYTA in MDD.
• The commercial success of CAPLYTA depends on market acceptance, reimbursement from third-party payers, and effective sales activities.
• There are risks associated with manufacturing and supply chain activities.
• The company may encounter unexpected safety or tolerability issues with CAPLYTA following commercial launch.
• There is a risk of generic competition before the expiration of patents.
• The company is subject to risks related to the COVID-19 pandemic, conflicts in Ukraine, Russia and the Middle East, global economic uncertainty, inflation, higher interest rates or market disruptions.

Future Outlook

The company anticipates working with the FDA during the review process for the sNDA and believes CAPLYTA has the potential to become a first-choice treatment for adjunctive MDD therapy if approved. The company also plans to continue clinical trials and development of other product candidates.

Management Comments

• Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies, stated that more than half of patients do not adequately respond to an antidepressant alone.
• Dr. Durgam also stated that given CAPLYTA's efficacy and safety profile, they believe CAPLYTA can become a first-choice treatment for the adjunctive treatment of MDD pending FDA approval.

Industry Context

This announcement is significant as it addresses a large unmet need in the treatment of major depressive disorder, where many patients do not respond adequately to first-line treatments. The potential approval of CAPLYTA for MDD could position Intra-Cellular Therapies as a key player in the psychiatric therapeutics market.

Comparison to Industry Standards

• The reported effect sizes of 0.61 and 0.56 in the MADRS scale for CAPLYTA are considered clinically meaningful and are comparable to or better than some other adjunctive therapies for MDD.
• The favorable safety profile, particularly the lack of significant metabolic and weight changes, is a positive differentiator compared to some other antipsychotics used in the treatment of depression.
• Companies like Alkermes with their drug Aristada, and Otsuka with Abilify Maintena, also target the psychiatric market, but CAPLYTA's unique mechanism of action and safety profile could give it a competitive edge if approved for MDD.

Stakeholder Impact

• Shareholders may see a positive impact on the stock price if the sNDA is approved.
• Patients with MDD may benefit from a new treatment option if CAPLYTA is approved.
• Employees of Intra-Cellular Therapies may see increased job security and growth opportunities.
• Physicians may have a new tool to treat patients with MDD.

Next Steps

• The company will work with the FDA during the review process for the sNDA.
• The company will continue to conduct clinical trials and development of other product candidates.

Key Dates

Keywords

CAPLYTA, lumateperone, Major Depressive Disorder, MDD, sNDA, FDA, antidepressant, psychiatry, clinical trials, CNS disorders