Psychiatry Month in Review: November 2024

Recent Submission to the FDA

Intra-Cellular Therapies Submits sNDA to FDA for Lumateperone as an MDD Adjunctive Therapy

Intra-Cellular Therapies recently submitted a supplemental New Drug Application (sNDA) to the FDA for lumateperone (CAPLYTA) as an adjunctive therapy to antidepressants for the treatment of MDD. If approved, this will expand the on-label use of lumateperone beyond the already-approved indications of adult schizophrenia and bipolar depression. The submission included 2 phase 3 global, double-blind, placebo-controlled studies that showed participants on lumatperone had a 4.9-point and 4.5-point reduction in depression symptoms, respectively (P < .0001; Cohen’s d effect = 0.56).

Phase 2 and 3 Data in the Psychiatry Pipeline

SPN-820 Decreases Depressive Symptoms Within Hours of First Dose in Phase 2a Trial

An open-label, phase 2a study revealed that participants on SPN-820 experienced meaningful reductions in depressive symptoms as early as 2 hours. SPN-820 demonstrated a clinically meaningful improvement of -6.1 at 2 hours and -9.6 at day 10 on the Hamilton Depression Rating Scale-6 items (HAM-D6). The study also showed that SPN-820 decreased suicidal ideation by 80%.

Supernus Pharmaceuticals presented this data on SPN-820, an oral first-in-class intracellular moderator of the mechanistic target of rapamycin complex 1, at Psych Congress 2024.

Phase 3 Data Shows TEV-‘749 Injection Improves Social Function in Schizophrenia

The Phase 3 Subcutaneous Olanzapine Extended-Release Injection Study (SOLARIS) showed TEV-‘749 significantly improved the social functioning and quality of life in adults with schizophrenia, announced by Teva on November 1, 2024, at Psych Congress 2024. The improvement of social functioning was demonstrated across 3 doses (TEV’749 318 mg, 425 mg, and 531 mg) in the mean change difference from week 4 to baseline in the Personal and Social Performance Scale (P < .05). The 318 mg dose had a statistically significant mean difference in change to week 4 (P < .05).

Phase 3 Data Shows Lumateperone Delays Schizophrenia Relapse Longer Than Placebo

Phase 3 data showed that patients with schizophrenia on lumateperone 42 mg had a significantly delayed relapse compared to patients on placebo, announced Intra-Cellular Therapies on November 5, 2024 (P = .0002). In the multicenter, multi-national, randomized, double-blind, placebo-controlled, parallel-group trial participants on lumateperone had 18 relapses (16.4%) compared with 44 relapses (38.6%) among the placebo group. Lumateperone was linked to a 63% reduction in the risk of relapse compared with placebo.

Emraclidine Fails to Significantly Reduce Schizophrenia Symptoms in Phase 2 EMPOWER Trials

In the phase 2 EMPOWER-1 and EMPOWER-2 trials, emraclidine, a once-daily oral monotherapy, did not bring statistically significant reductions in the positive and negative symptoms of schizophrenia. In EMPOWER-1, patients on emraclidine 10 mg and 30 mg had a Least Squares Mean difference in the Positive and Negative Syndrome Scale (PANSS) total score of -14.7 and -16.5, respectively, compared with – 13.5 for patients on placebo. Despite the negative results, the team plans to continue analyzing the data to determine the next steps.

A concerning association between antipsychotics for schizophrenia and mortality

Can Antipsychotics Increase Mortality Risk? A New Study Shows It Might

A study showed that, after controlling for immortal time bias, high-dose antipsychotic use for schizophrenia was linked to an increased mortality risk (P = .008). The mortality rate varied by exposure level: nonuse (5.5%), low (5.8%), moderate (5.4%), and high (7%) (P = .001). Conversely, antidepressants reduced the mortality risk, but only for high doses (P = .047).