onfasprodil intravenous (MIJ821 IV) / Novartis - LARVOL DELTA

Emerging trends in antipsychotic and antidepressant drug development: Targeting nonmonoamine receptors and innovative mechanisms. (PubMed, PCN Rep) - "One noteworthy candidate is Ulotaront (SEP-363856), an agent acting as a TAAR1 agonist with 5-HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side-effects. Similarly, MIN-101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)-approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor-positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK-653 (NBI-1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric..."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry • Schizophrenia

An Open-label, Adaptive Design, Positron Emission Tomography Study in Healthy Male Participants to Characterize Receptor Occupancy by MIJ821 in the Brain (clinicaltrials.gov) - P1 | N=11 | Completed | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose). (PubMed, Clin Transl Sci) - "In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose-dependent."

Journal • P1 data • CNS Disorders

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=200 | Terminated | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2024 ➔ Sep 2023 | Active, not recruiting ➔ Terminated; Terminated by Novartis

Trial completion date • Trial termination • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=195 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Terminated ➔ Active, not recruiting | Trial completion date: Jul 2023 ➔ Aug 2024

Enrollment closed • Trial completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=199 | Terminated | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2024 ➔ Jul 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Jul 2023; Terminated by sponsor

Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=199 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2024 ➔ Mar 2023

Enrollment closed • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=195 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2024 ➔ Aug 2024 | Trial primary completion date: May 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

An Open-label, Adaptive Design, Positron Emission Tomography Study in Healthy Male Participants to Characterize Receptor Occupancy by MIJ821 in the Brain (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: May 2023 ➔ Nov 2023 | Trial primary completion date: Apr 2023 ➔ Nov 2023

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

An Open-label, Adaptive Design, Positron Emission Tomography Study in Healthy Male Participants to Characterize Receptor Occupancy by MIJ821 in the Brain (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Study of efficacy, safety, tolerability and pharmacokinetics of MIJ821 in participants with treatment- resistant depression (TRD) Estudio de eficacia, seguridad, tolerabilidad y farmacocinética de MIJ821 en participantes con depresión resistente al tratamiento (DRT). (clinicaltrialsregister.eu) - P2 | N=56 | Ongoing | Sponsor: Novartis Farmacéutica, S.A.

New P2 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2 | N=195 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2024 ➔ May 2024 | Trial primary completion date: Jan 2024 ➔ May 2024

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Discovery and first disclosure of MIJ821, a novel, rapidly acting antidepressant (ACS-Fall 2022) - "Recently, an intranasal formulation of the -S- form of ketamine, esketamine, an NMDA receptor blocker, was approved as a rapidly acting antidepressant agent.We have identified an NMDA NR2B subunit selective, negative allosteric modulator (NAM), with rapidly acting antidepressant clinical activity. We will present the discovery of MIJ821 in collaboration with biotech partners. We will include a story of scaffold morphing from a literature lead, balancing properties, in particular hERG and PGP efflux to ensure brain exposure, a target engagement imaging strategy, and a summary of the Phase 1 and Phase 2 clinical data that has led to this molecule moving into full clinical development."

CNS Disorders • Depression • Psychiatry

Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry. (PubMed, Pharmacopsychiatry) - "These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed."

Clinical • Journal • P2 data • P3 data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2; N=195; Recruiting; Sponsor: Novartis Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

[VIRTUAL] Efficacy and Safety of MIJ821 in Patients With Treatment-Resistant Depression: Results From a Randomized, Placebo-Controlled, Proof-of-Concept Study (APA 2021) - P2 | "MIJ821 is a novel N-methyl-D-aspartate (NMDA) negative allosteric modulator selective for the NR2B subunit, with a potentially low rate of the psychotomimetic side effects that limit the therapeutic utility of ketamine in TRD. In this proof-of-concept study, MIJ821 was associated with a significant improvement in MADRS score vs. placebo in patients with TRD. No new safety signals were identified."

Clinical • Anesthesia • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

[VIRTUAL] Efficacy and safety of MIJ821 in patients with treatment-resistant depression: Results from a randomized, placebo-controlled, proof-of-concept study (EPA 2021) - P2 | "Introduction MIJ821 is a novel N-methyl-D-aspartate (NMDA) receptor antagonist, with a potentially low rate of the psychotomimetic side effects that limit the therapeutic utility of ketamine in treatment-refractory depression (TRD).  Objectives To assess efficacy and safety of MIJ821.  Methods Adults with TRD (>2 prior treatment failures; Montgomery-Asberg Depression Rating Scale [MADRS], >24) were eligible and were randomized (n=70) to low versus high doses of MIJ821, with two dosing regimens of weekly or biweekly, versus ketamine versus placebo. This study was funded by Novartis. Clinical trial.gov: NCT03756129"

Clinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent (clinicaltrials.gov) - P2; N=195; Not yet recruiting; Sponsor: Novartis Pharmaceuticals

Clinical • New P2 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

Novartis snaps up neuro partner Cadent for $210M upfront with promise of up to $560M more (FierceBiotech) - "Novartis will acquire all of Cadent’s outstanding stock in exchange for the upfront fee and up to $560 million in milestone payments. The duo expects the deal to close in the first quarter of 2021. Under the deal, Novartis will buy out the milestones and royalties for the depression asset, MIJ821, which it is testing in a phase 2 study. It also picks up CAD-9303, a treatment for schizophrenia..."

M&A • CNS Disorders • Depression • Schizophrenia

Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression (clinicaltrials.gov) - P2; N=72; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Depression • Mood Disorders • Psychiatry

Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression (clinicaltrials.gov) - P2; N=72; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed