April 2026 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.

Phase 3 Brilliance Studies Initiated on Alixorexton for the Treatment of Narcolepsy Type 1 and Type 2

At the beginning of the month, Alkermes announced the initiation of the Brilliance Studies, a phase 3 program evaluating the safety and efficacy of alixorexton compared with placebo in adults with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, NT2, and idiopathic hypersomnia (IH).

LPCN 1154 for Postpartum Depression Fails to Meet Phase 3 Primary Endpoint

Topline results from Lipocine’s phase 3 placebo-controlled trial evaluating oral brexanolone (LPCN 1154) for the treatment of postpartum depression. LPCN 1154 did not show a statistically significant reduction from baseline in Hamilton Depression Rating Scale (HAM-D) 17-item total score compared with placebo at hour 60 in the full analysis set, thus failing to meet the primary endpoint.

GlyphAgo for Treatment of Anxiety Shows Positive Phase 1 Topline Results

GlyphAgo (SPT-320), a modified form of agomelatine, showed proof-of-concept in topline phase 1 results. The drug attained therapeutic levels of agomelatine at lower doses than unmodified agomelatine, reducing potentially harmful liver exposure and the need for liver testing.

Encouraging Pharmacodynamic Data From Phase 2 Clinical Trial of AL001

Alzamend Neuro today announced encouraging pharmacodynamic findings from a brain magnetic resonance spectroscopy (MRS) analysis conducted in healthy participants (N=6) in a clinical trial of AL001 conducted at Massachusetts General Hospital. AL001 is a patented ionic cocrystal formulation of lithium combined for delivery with L-proline and salicylate, designed to deliver a full therapeutic amount of lithium to the brain with less systemic exposure than lithium carbonate. It is currently being studied as a treatment for Alzheimer disease, bipolar disorder type 1, major depressive disorder, and posttraumatic stress disorder.

First Participants Enrolled in Phase 2a Study of BXCL501 for Treatment of Acute Stress Reactions

BioXcel Therapeutics announced the enrollment of the first participants in a US Department of War-funded phase 2a clinical trial evaluating sublingual dexmedetomidine (BXCL501) for the treatment of acute stress reactions (ASR), also known as acute stress disorder. The double-blind, placebo-controlled trial is designed to enroll 100 participants experiencing ASRs following motor vehicle collisions and will investigate the potential of BXCL501 to reduce ASR symptom severity, improve neurocognitive function, and prevent the progression to chronic posttraumatic neuropsychiatric symptoms.

BPL-003 for Treatment Resistant Depression Continues to Show Sustained Symptom Reduction

Results of part 2 from the phase 2a study pf BPL-003 for treatment-resistant depression showed rapid and sustained reductions in symptoms. The data included participants taking selective serotonin reuptake inhibitors (SSRIs), and part 2 analysis has been published in CNS Drugs. The phase 2a study was a 12-week open-label, ascending-dose trial with 12 adult participants aged 18 to 75 with moderate to severe major depressive disorder and treatment-resistant depression. The severity of the disorder was classified by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 24 or higher. All participants had a history of 2 or more failed courses of antidepressants and continued on a stable dose of an SSRI (citalopram, escitalopram, sertraline, or fluoxetine) throughout the study. Half of participants received a single 10 mg dose of BPL-003, while half received a single 12 mg dose. Participants were then monitored for 12 weeks.

Lybalvi Associated With Improvement in Negative Symptoms of Schizophrenia: Findings From Long-Term Analysis

This month, Alkermes announced the publication of a 56-week post hoc analysis of the effects of olanzapine and samidorphan (Lybalvi) on negative symptoms in adults living with schizophrenia, which found that treatment with Lybalvi was associated with significant and durable improvement in mean negative symptom scores. Lybalvi is currently approved in the US for the treatment of schizophrenia in adults, for the treatment of bipolar I disorder in adults, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, and as monotherapy or as adjunct to lithium or valproate.

New US Grant Program Announced for Post-Approval COMP360 Provider Training

Compass Pathways today announced an invitation for US based organizations to apply for a grant to create training content for health care providers who want to be able to deliver investigational COMP360 psilocybin treatment, if COMP360 is approved. While many high-quality training organizations have already trained thousands of health care providers in core and psilocybin-specific psychedelic care, this particular grant program will support the development of high-quality training content, including a COMP360-specific module, with the aim of ensuring health care providers are well-prepared to care for patients receiving COMP360 following its potential commercial launch.

Ongoing Trial for PBFT02 Shows Improvement of Frontotemporal Dementia With Granulin Mutations

Updated phase 1/2 clinical trial data on PBFT02, a cerebrospinal fluid injection, shows slowed neurodegeneration in patients with frontotemporal dementia with granulin mutations. A recent type C meeting with developers, Passage Bio, and the FDA recommended a randomized controlled trial of the medication as a next step, which the company has not confirmed due to ethical and logistical questions.

New AAN Poster Presentation on Alixorexton for Narcolepsy Type 1: Improvement in Disease Severity, Cognitive Functioning, and Fatigue

In a poster presentation at the American Academy of Neurology (AAN) 2026 Annual Meeting, investigators presented additional data from the Vibrance-1 phase 2 study of alixorexton in patients with narcolepsy type 1 (NT1). According to the results, participants with NT1 taking once-daily alixorexton demonstrated nominally significant, clinically meaningful improvements in patient-reported disease severity, cognitive impairment, and fatigue, with improvements sustained through 12 to 13 weeks. Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH).

EMP-01 for Social Anxiety Disorder Demonstrates Meaningful Improvements in Phase 2a Study

AtaiBeckley announced expanded phase 2a results for oral R-MDMA (EMP-01) in adults with social anxiety disorder (SAD), which show that EMP-01 demonstrated clinically meaningful and consistent improvements across clinician-rated symptoms, patient-reported experience, and real-world behavioral outcomes. The multi-center study enrolled 71 adult participants with moderate-to-severe SAD across 7 clinical sites in the UK. Participants were randomly assigned to receive 2 in-clinic administrations of EMP-01 (225 mg) or placebo, given 28 days apart, with no adjunctive psychotherapy; 70 participants received at least 1 dose of study drug and 69 completed the day 43 efficacy assessments. All clinician-rated assessments were conducted by blinded central raters. Topline results from this study were previously reported in February 2026.

FDA Fast-Tracks Psychedelic Therapies for Depression, PTSD, and Alcohol Use Disorder

The FDA announced a series of regulatory actions aimed at accelerating development of psychedelic-based treatments for serious mental illness following the recent executive order directed at the US Department of Health and Human Services. The moves include issuance of priority review vouchers, clearance of new early-phase clinical research, and forthcoming guidance on trial design for serotonin-2A agonists and related compounds. The actions signal a notable escalation in federal support for investigational therapies for psychiatric disorders where current pharmacological options are lacking.

FDA Approves sNDA of Caplyta for the Prevention of Relapse in Schizophrenia

The FDA has approved a supplemental New Drug Application based on long-term data evaluating the safety and efficacy of Johnson & Johnson’s lumateperone (Caplyta) for the prevention of relapse in schizophrenia, further reinforcing the long-term efficacy and tolerability of Caplyta. In the phase 3, double-blind, randomized withdrawal trial supporting this update, Caplyta significantly extended time to relapse vs placebo during the 26-week double-blind treatment period (P=0.0002), helping support long-term stability for adults living with schizophrenia. Participants treated with Caplyta had a 63% lower risk of relapse compared with placebo (hazard ratio = 0.37), and 84% of participants were relapse-free over 6 months. Caplyta also significantly delayed time to all-cause treatment discontinuation, including relapse.

AD04 Application Submitted to FDA Commissioner’s National Priority Voucher Pilot Program for Potential Expedited Review

Adial Pharmaceuticals has announced the submission of the AD04 product application for consideration of the FDA Commissioner’s National Priority Voucher Pilot Program (CNPV). The CNPV program was announced in June 2025 and is designed to speed up the FDA review process for drugs that address 1 of 5 key US national health priorities. The program also utilizes a collaborative review approach, where experts meet to discuss cases and help evaluate applications more efficiently.

Patent Issued for Novel Genetic Biomarker DGM4: Identified Through Liafensine Program for Treatment-Resistant Depression

The United States Patent and Trademark Office has issued patent number 12,612,261, titled “Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters,” for the use of Denovo Biopharma’s DGM4. DGM4 is a novel genetic biomarker discovered through Denovo’s artificial intelligence and big data based Denovo Genomic Marker platform for the liafensine (DB104) program for treatment-resistant depression.

FDA Approves Auvelity for Treatment of Agitation in Alzheimer Disease

The FDA has approved Axsome Therapeutics’ oral dextromethorphan-bupropion (Auvelity, formerly known as AXS-05) for the treatment of agitation associated with Alzheimer disease (AD). Auvelity is a first-in-class treatment for AD agitation which targets the N-methyl D-aspartate (NMDA) and sigma-1 receptors.

Be sure to follow us on LinkedIn, Facebook, or X, or subscribe to our eNewsletters to stay up to date with the latest news.