November in Review: Updates on the Psychiatric Treatment Pipeline

Take a look at this month’s developments in the psychiatric treatment pipeline. We compiled a recap of the latest news here, just in case you missed any of the updates.

sNDA Submitted for AXS-05 for the Treatment of Alzheimer Disease Agitation

Axsome Therapeutics announced they have submitted a supplemental NDA (sNDA) to the US Food and Drug Administration (FDA) for dextromethorphan-bupropion (AXS-05) for the treatment of Alzheimer disease agitation. AXS-05 is Axsome’s novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor being developed for the treatment of Alzheimer disease agitation and smoking cessation. AXS-05 was granted FDA Breakthrough Therapy designation for Alzheimer disease agitation back in 2020, the second Breakthrough Therapy designation granted to Axsome for AXS-05 (the first being for major depressive disorder).

FDA Approves Caplyta for Adjunctive Treatment of Major Depressive Disorder

The FDA has approved Johnson & Johnson’s lumateperone (Caplyta) as an adjunctive therapy for the treatment of adults with major depressive disorder. The 2 phase 3 double-blind, placebo-controlled clinical trials submitted to the FDA, studies 501 and 502, both demonstrated a significantly superior improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 6 compared with placebo at the dose of 42 mg per day. Study 501, which included 485 patients, demonstrated a 4.9-point decrease in the MADRS score for patients on Caplyta vs to an oral antidepressant plus placebo who all continued on their primary prestudy antidepressant. Study 502, which included 480 patients, demonstrated a 4.5-point decrease in the MADRS score for patients on Caplyta vs placebo who all continued on their primary prestudy antidepressant.

BPL-003: Positive Phase 2b Open-Label Extension Study Data

AtaiBeckley today announced positive topline results from the open-label extension study of a phase 2b clinical trial (NCT05870540) of intranasal mebufotenin benzoate (BPL-003) in patients with treatment-resistant depression. Investigators found that a 12 mg dose of BPL-003 administered 8 weeks after a 0.3 mg, 8 mg, or 12 mg dose of BPL-003 was generally well-tolerated and provided additional rapid, clinically meaningful antidepressant effects, which were sustained for up to 8 weeks.

A “Surprise” Miss: NBI-1070770 for Major Depressive Disorder Fails in Phase 2 Study

Neurocrine Biosciences announced that its phase 2 study evaluating the efficacy, safety, and tolerability of NBI-1070770 in adults with major depressive disorder (MDD) did not meet the primary endpoint compared to placebo. Investigators of this signal-seeking study enrolled 73 adult participants with a diagnosis of MDD who did not adequately respond to at least 1 antidepressant in their current course of treatment. NBI-1070770 is an investigational selective, orally active, negative allosteric modulator of the NR2B subunit-containing N-methyl-D-aspartate receptor.

Austedo Phase 4 Data Shows Reduction in Tardive Dyskinesia Severity

Phase 4 data from Teva Pharmaceuticals on deutetrabenazine (Austedo) showed significant reduction in involuntary movement and improvements in quality of life in adults with tardive dyskinesia. Up to 77% of participants taking Austedo reported that after 3 months there were meaningful improvements in impacts of tardive dyskinesia.

Alixorexton for Treatment of Narcolepsy Type 2: New Positive Phase 2 Data

Alkermes announced positive topline results from the Vibrance-2 dose-ranging phase 2 study evaluating alixorexton in patients with narcolepsy type 2 (NT2). Alixorexton, formerly referred to as ALKS 2680, is a novel, investigational, oral, selective orexin 2 receptor agonist in phase 2 development for the treatment of narcolepsy type 1, NT2, and idiopathic hypersomnia. In Vibrance-2, participants with NT2 (n=93) were randomly assigned (1:1:1:1) to receive a once-daily dose of alixorexton (10 mg, 14 mg, or 18 mg) or placebo for 8 weeks. Once-daily alixorexton met the dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements from baseline compared with placebo on the Maintenance of Wakefulness Test and Epworth Sleepiness Scale at week 8.

Iclepertin Found Ineffective in Treating Cognitive Impairment Associated With Schizophrenia

n an analysis of 3 phase 3 trials, iclepertin showed no significant improvement in cognitive impairment for adults with schizophrenia. The drug was well tolerated but did not result in significant changes in cognition in patients with schizophrenia. The analysis included the CONNEX 1, 2, and 3, trials—all randomized, double-blind, placebo-controlled phase 3 studies conducted across 41 countries. Patients were randomized 1:1 to oral iclepertin 10 mg or placebo once daily for 26 weeks. At week 26, there was no significant difference between treatment and placebo groups in individual trials or the pooled population. The adjusted mean difference for drug vs placebo in MCCB overall composite T-score was 0.127 (P=0.63)

Planned FDA Investigational New Drug Application: SPC-15 for the Treatment of PTSD

Silo Pharma today announced that it has chosen to partner with Allucent, a global full-service clinical research organization, to support their planned submission of an investigational new drug application to the FDA for a phase 1 clinical trial of SPC-15 for the treatment of posttraumatic stress disorder (PTSD). SPC-15 is a its intranasal prophylactic and novel serotonin 4 (5-HT4) receptor agonist that utilizes biomarkers for the treatment of PTSD, anxiety, and other stress-induced affective disorders.

Tonmya Available Commercially for Treatment of Fibromyalgia

Tonix Pharmaceuticals announced that Tonmya (cyclobenzaprine HCl) is now available by prescription in the United States. The treatment was approved by the FDA in August of 2025 and is now commercially available. The most recent phase 3 trial for this drug showed significant improvements in symptoms and functioning for patients with fibromyalgia. The trial, RESILIENT, showed significant improvement (P < .001) in daily pain intensity scores at week 14. The study also showed improvement (P < .001) in Patient Global Impression of Change scores, Fibromyalgia Impact Questionnaire (Revised) Symptoms and Function domains, Patient Reported Outcomes Measurement Information System instruments for Sleep Disturbance and Fatigue, and daily diary sleep quality scores.

New Review on VMAT2 Inhibitors and Ingrezza for Treatment of Tardive Dyskinesia

Neurocrine Biosciences has announced publication of a narrative review paper on FDA-approved vesicular monoamine transporter 2 (VMAT2) inhibitors Ingrezza (valbenazine) and deutetrabenazine. The review covers clinical research on these drugs for treatment of tardive dyskinesia and highlights the unique profile of Ingrezza. Ingrezza and deutetrabenazine were noted to have key differences. Both medications target VMAT2 receptors, but Ingrezza was found to work with a single metabolite with high affinity for VMAT2 and had no off-target receptor activity.

Phase 3 Trial of LPCN 1154 for Postpartum Depression Shows Positive Progress

Lipocine announced completion of a scheduled independent review by the Data Safety Monitoring Board of the ongoing phase 3 trial of LPCN 1154 (oral brexanolone) for treatment of postpartum depression. The board recommended the trial continue with no modifications, after 30 patients completed at least the 7 day follow up visit. The current phase 3 trial is a randomized, double-blind study evaluating LPCN 1154 in women 15 to 45 years old diagnosed with severe postpartum depression.

FDA Clears Investigational New Drug Application for TNX-102 SL for Treatment of Major Depressive Disorder

Tonix Pharmaceuticals announced that the FDA has cleared the Investigational New Drug application for development of TNX-102 SL (cyclobenzaprine hydrochloride) for treatment of major depressive disorder in adults. With millions of patients suffering from bipolar disorder every year, this investigation may provide a new treatment option for major depressive disorder.

New Drug Application Submitted for Centanafidine for Treatment of ADHD

Otsuka Pharmaceutical has submitted a new drug application to the FDA for centanafadine for treatment of attention deficit hyperactive disorder (ADHD) in children, adolescents, and adults. Centanafadine is the first investigational norepinephrine, dopamine, and serotonin reuptake inhibitor for ADHD therapy. NDA submission for this drug is based on results from 4 phase 3 clinical trials which evaluated the efficacy and safety of centanafadine. In these phase 3 studies, centanafadine showed statistically significant and clinically meaningful improvements in symptoms of ADHD.

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