The Psychiatric Pipeline in Review: Quarter 1, 2025

The first quarter of 2025 saw some huge successes and fails in the psychiatric treatment pipeline. Here, learn more about what percentage of that news was positive vs negative, what disease states were most prominently featured, and what treatments you should keep an eye on.

What percentage of 2025 psychiatric pipeline news was positive vs negative? The news this quarter was overwhelmingly positive, with approximately 86.4% good news.

What disease states are most prominently featured in recent research? The top 5 disease states this quarter were major depressive disorder (25%), schizophrenia (18.8%), Alzheimer disease (18.8%), and treatment-resistant depression (18.8%).

Check out all the specifics of our coverage from the from the first quarter below.

Navacaprant for Major Depressive Disorder Fails in Late-Stage Study

The oral kappa opioid receptor antagonist navacaprant for the treatment of major depressive disorder failed in a phase 3 study as part of Neumora Therapeutics' pivotal KOASTAL program. Both navacaprant and placebo showed similar improvements in depression scores, with no significant difference. Women showed a slightly better response to navacaprant compared to placebo, warranting further investigation.

LB-102 for Schizophrenia Sees Positive Phase 2 Topline Results

LB Pharmaceuticals announced positive topline results from NOVA1, a phase 2 dose finding trial evaluating N-methyl amisulpride (LB-102), a once-daily orally administered novel dopamine D_2/3/5-HT₇ inhibitor and potential first-in-class benzamide antipsychotic, in adult patients with acute schizophrenia. LB-102 demonstrated significant efficacy in reducing PANSS scores in acute schizophrenia, with varying effect sizes across doses. The safety profile of LB-102 was favorable, showing low incidence of extrapyramidal symptoms and minimal adverse effects.

FDA Grants Fast Track Designation to Posdinemab for Early Alzheimer Disease

The US Food and Drug Administration granted Fast Track designation to posdinemab, a phosphorylated tau-directed monoclonal antibody being investigated for the treatment of patients with early Alzheimer disease in the phase 2b AuTonomy study. Posdinemab's unique binding to the mid-domain of tau differentiates it from other anti-tau antibodies, potentially enhancing its effectiveness.

FDA Grants Breakthrough Device Designation to pTau 217 Blood Test for Alzheimer Disease

The US Food and Drug Administration granted Breakthrough Device Designation to Spear Bio’s pTau 217 blood test for Alzheimer disease. The pTau 217 blood test offers a noninvasive alternative for Alzheimer's diagnosis, distinguishing it from other neurodegenerative disorders. Spear Bio's SPEAR technology enhances diagnostic accuracy by minimizing nonspecific interactions, allowing for precise biomarker measurements.

FDA Accepts Biologics License Application for Lecanemab-irmb

The US Food and Drug Administration accepted Eisai's Biologics License Application for lecanemab-irmb (Leqembi) subcutaneous autoinjector for weekly maintenance dosing. Lecanemab-irmb subcutaneous autoinjector offers a home-administered Alzheimer's treatment, potentially reducing hospital visits and simplifying care. The Clarity study demonstrated a 14% increase in amyloid plaque removal with subcutaneous administration compared to IV.

Esketamine CIII Nasal Spray: First and Only Monotherapy for Treatment-Resistant Depression

The US Food and Drug Administration has approved the Johnson & Johnson supplemental New Drug Application for esketamine (Spravato) CIII nasal spray, the first and only monotherapy for adults with treatment-resistant depression, defined as inadequate response to at least 2 oral antidepressants. Spravato reduces symptoms of depression in as little as 24 hours and reduces the time to relapse for patients who stay on treatment. The approval is based on a study showing significant improvement in depression scores compared with placebo, with a consistent safety profile.

Phase 3 Study Initiated: Osavampator as Adjunctive Therapy for Major Depressive Disorder

Neurocrine Biosciences just announced the initiation of a phase 3 registrational study to evaluate the efficacy, safety, and tolerability of osavampator, an investigational drug under development as an adjunctive treatment to antidepressants for major depressive disorder. Investigators will enroll adults with a primary diagnosis of major depressive disorder who have inadequate response to current, oral antidepressant treatment.

BPL-003 for Alcohol Use Disorder: Positive Topline Results of Phase 2A Study

Beckley Psytech today announced positive topline results from their open-label phase 2A study of BPL-003 in participants with moderate-to-severe alcohol use disorder, which show that treatment with BPL-003 can induce meaningful and sustained reductions in alcohol use and heavy drinking days for up to 3 months following a single dose. BPL-003 significantly reduced alcohol consumption and increased abstinence in participants with moderate-to-severe alcohol use disorder over a 12-week period.

AD04 for Alcohol Use Disorder: New Positive Results From Pharmacokinetics Study

Adial Pharmaceuticals announced the completion of a pharmacokinetics study of AD04, an investigational selective serotonin-3 receptor (5-HT3) antagonist being developed for the treatment of alcohol use in patients with a 5-HT3 genomic biomarker. These study results support the near micro-dosing regimen planned for use in the upcoming registration trials for AD04 and make up the regulatory submission for the US Food and Drug Administration.

Targeting the Brain: A New Path Forward for IBS Treatment

A new study shows that opioid delta-receptor (DOP) agonists target the central nervous system, potentially alleviating irritable bowel syndrome (IBS) symptoms linked to psychological stress. A novel animal model demonstrated that DOP agonists regulate glutamate neurotransmission in the insular cortex, improving IBS symptoms. This suggests that DOP agonists may offer a more definitive IBS treatment with minimal adverse effects compared with current therapeutic options.

CYB003 for the Adjunctive Treatment of Major Depressive Disorder

CYB003, a deuterated psilocybin molecule, is being evaluated for major depressive disorder (MDD) in the PARADIGM phase 3 program, aiming for a paradigm shift in depression treatment. The program includes 3 pivotal studies: APPROACH, EMBRACE, and EXTEND, targeting patients with moderate to severe MDD who inadequately respond to current antidepressants. In current phase 2 trials, participants showed significant symptom improvement and high remission rates with CYB003. This supports the phase 3 design's focus on durable, intermittent treatment. Additionally, CYB003 was well tolerated with no serious adverse events, indicating a favorable safety profile for potential future use in MDD treatment.

Patent Issued for Methods of Identifying Patients With Substance Use-Associated Genetic Markers, Treatment With AD04

The United States Patent and Trademark Office issued patent number 12,221,654 for Adial Pharmaceuticals’ identification of patients with specific genetic markers linked to substance use disorders and treatment with AD04. AD04 targets patients with the TT genotype of rs1042173 in the serotonin transporter gene, addressing opioid and alcohol use disorders. Pharmacokinetics research supports AD04's micro-dosing regimen, showing proportional ondansetron exposure and administration flexibility with or without food.

SPN-820 Fails to Meet Primary Endpoint in Study of Adults with Treatment-Resistant Depression

SPN-820 did not achieve significant improvement in treatment-resistant depression in a phase 2b study, failing its primary endpoint of change from baseline. The study examined the efficacy and safety of SPN-820 over a course of 4 weeks of treatment and then a week of blinded placebo-washout in approximately 250 patients from approximately 40 clinical sites. The primary outcome measure was the change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score to week 4; SPN-820 did not achieve statistically significant improvement (SPN-820 [LS mean ± Standard Error]: -12.3 ± 0.96 vs placebo: -11.9 ± 0.96; P = not significant). There was no treatment difference between SPN-820 and placebo in the change from baseline to week 4 for the secondary endpoints.

FDA Approves of Label Changes for Sublocade Injection for Opioid Use Disorder

The US Food and Drug Administration (FDA) approved of key modifications to the administration protocol for injectable long-acting opioid use disorder treatment buprenorphine (Sublocade). These key modifications include a rapid treatment initiation protocol and expanded alternative injection site options. Expanded injection site options for Sublocade include abdomen, thigh, buttock, and back of the upper arm, enhancing treatment flexibility. These changes aim to improve patient adherence and outcomes, aligning treatment with real-world clinical needs.

Positive FDA Feedback for Proposed In Vitro Bridging Strategy for Alcohol Use Disorder Treatment, AD04

The FDA gave positive feedback to Adial Pharmaceuticals regarding its proposed in vitro bridging strategy for the phase 3 formulation of AD04, an investigational selective serotonin-3 receptor (5-HT3) antagonist. The FDA agreed with Adial’s proposed 505(b)(2) bridging strategy of leveraging the results from the relative bioavailability food-effect study, AD04-103, along with in vitro dissolution data demonstrating equivalence between the comparison product and the planned commercial formulation of AD04. Even though the final determination will depend on a comprehensive review of the complete New Drug Application, the FDA’s agreement represents a significant regulatory milestone for Adial. After securing this regulatory confirmation, Adial will proceed with manufacturing clinical supply materials in preparation for the upcoming phase 2 clinical program in 2025.

FDA Officially Removes REMS Requirement for Clozapine

The FDA announced it will eliminate the risk evaluation and mitigation strategies (REMS) program for clozapine and does not expect prescribers, pharmacies, and patients to report results of absolute neutrophil count (ANC) blood tests before pharmacies dispense clozapine. Despite removing REMS, the FDA still advises monitoring ANC levels, maintaining safety warnings in prescribing information. This decision is expected to decrease health care burdens and improve clozapine access, with manufacturers updating prescribing information accordingly.

BHV-7000 for Bipolar Disorder Fails in Phase 2/3 Trial

Biohaven’s pipeline drug BHV-7000, a selective activator of Kv7.2/7.3 potassium channels, failed to meet the primary endpoint in a pivotal phase 2/3 bipolar trial. While BHV-7000 failed to achieve statistical significance in this bipolar trial, the 75 mg dose was safe and well-tolerated with no serious adverse events. Despite this setback, Biohaven is currently evaluating BHV-7000 for other disease states, including a phase II trial (NCT06419608) in major depressive disorder, focal epilepsy, and generalized epilepsy.

BLP-003 for Treatment-Resistant Depression: Phase 2b Patient Enrollment Completed

In early March, atai Life Sciences announced the completion of patient enrollment for an 8-week, double-blind, core stage of the global phase 2b clinical trial evaluating BPL-003, an intranasal mebufotenin benzoate formulation for treatment-resistant depression. The trial involves 196 patients across 38 sites. This formulation of BPL-003 is administered via a nasal spray device used in a previously approved drug product, and is designed to deliver rapid and durable effects in a single dose and a short time in clinic.

Phase 1 Study Initiated: NBI-1140675 for Neurological and Neuropsychiatric Conditions

Neurocrine Biosciences announced the initiation of a phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of investigational compound NBI-1140675 in healthy adult participants. NBI-1140675 is an oral, selective second-generation small molecule inhibitor of the vesicular monoamine transporter 2 in development for the potential treatment of certain neurological and neuropsychiatric conditions, such as tardive dyskinesia.

Phase 2 Clinical Trial of AL001 for Major Depressive Disorder: Initiation Date Set for Late 2025

Alzamend announced plans to initiate a highly anticipated phase 2 clinical study of AL001, a novel lithium-delivery system for the treatment of patients with major depressive disorder, in late 2025. AL001 is designed to enhance lithium delivery to the brain, reducing exposure to other organs and improving safety compared with current lithium salts. The phase 2 trial will explore AL001's potential to eliminate the need for therapeutic drug monitoring, a significant burden with current lithium treatments. AL001 could significantly impact the treatment paradigm for MDD, offering a safer, more effective, and user-friendly option for patients.

New 48-Week Remission Data on Ingrezza for the Treatment of Tardive Dyskinesia

Neurocrine Biosciences shared new data from the long-term, open-label KINECT 4 study demonstrating remission of tardive dyskinesia among most patients treated with once-daily valbenazine (Ingrezza) capsules. Ingrezza showed high efficacy in inducing tardive dyskinesia remission, with 59.2% of participants achieving remission after 48 weeks of treatment. Both 40 mg and 80 mg doses of Ingrezza significantly improved Abnormal Involuntary Movement Scale scores, with consistent remission rates across psychiatric diagnoses.

Phase 3 Trial Success: Solriamfetol for the Treatment of Adults With ADHD

Axsome Therapeutics announced that the FOCUS phase 3 trial of solriamfetol for the treatment of attention-deficit/hyperactivity disorder (ADHD) achieved its primary and key secondary endpoints, demonstrating statistically significant improvements in ADHD symptoms and disease severity compared with placebo. Results demonstrated that solriamfetol was able to reduce mean ADHD symptom burden by nearly 50%, which contributed to significant reductions in disease severity.

Phase 2 Trial Open Enrollment for SPG302, First Synaptic Regenerative Approach to Treat Schizophrenia

Spinogenix announced open enrollment for the phase 2 trial of SPG302, the first synaptic regenerative approach to treat schizophrenia with the potential to improve outcomes across all symptom domains. SPG302 is a once-a-day pill being developed as the first synaptic regenerative approach to treat schizophrenia with the potential to improve outcomes across all symptom domains. SPG302 represents a new, regenerative medicine approach to schizophrenia treatment that aims to restore glutamatergic synapses in regions of the brain affected by the disease.

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