osavampator (TAK-653) / Takeda, Neurocrine - LARVOL DELTA

Long-Term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

NBI-1065845-MDD3026: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

NBI-1065845-MDD3025: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

NBI-1065845-MDD3025: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Neurocrine Biosciences | Trial completion date: Nov 2026 ➔ Jul 2027 | Trial primary completion date: Nov 2026 ➔ Jul 2027

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

Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Neurocrine Biosciences Announces Amendment to Strategic Collaboration with Takeda to Develop and Commercialize Osavampator (formerly NBI-1065845/TAK-653) (PRNewswire) - "Under the amended agreement, Neurocrine will obtain exclusive rights for all indications to develop and commercialize osavampator, a potential first-in-class AMPA positive allosteric modulator in development for patients with inadequate response to treatment of major depressive disorder (MDD) in all territories worldwide except Japan, where Takeda will reacquire exclusive rights. Under the terms of the updated agreement, each company is responsible for development costs in their respective region, and both companies are eligible to receive royalty payments....'With the recent successful completion of our End-of-Phase 2 meeting with FDA for osavampator, we look forward to beginning the Phase 3 program in the first half of this year'."

Licensing / partnership • New P3 trial • Major Depressive Disorder

Neurocrine Biosciences Provides Update on ERUDITE Phase 2 Data for Luvadaxistat in Adults with Cognitive Impairment Associated with Schizophrenia (PRNewswire) - P2 | N=216 | ERUDITE (NCT05182476) | Sponsor: Neurocrine Biosciences | "Neurocrine Biosciences, Inc...today announced that its ERUDITE Phase 2 clinical study of investigational compound luvadaxistat (NBI-1065844) failed to meet its primary endpoint as a potential treatment to improve cognitive impairment in patients with schizophrenia....The ERUDITE study was the second Phase 2 trial for luvadaxistat. It failed to replicate the cognitive endpoints data seen in the earlier INTERACT study, due in part to the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms....We therefore plan to halt further development of luvadaxistat at this time and instead will focus our efforts and resources on the advancement into Phase 3 clinical development of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder."

New P3 trial • P2 data • Major Depressive Disorder • Schizophrenia

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

Effects of the selective AMPA modulator NBI-1065845 on the pharmacokinetics of midazolam or ethinyl estradiol-levonorgestrel in healthy adults. (PubMed, Clin Transl Sci) - "These findings indicate that NBI-1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI-1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SAVITRI: Study to Assess the Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P2 | N=183 | Completed | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Completed

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

SAVITRI: Study to Assess the Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P2 | N=183 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Effects of the Selective Ampa Modulator NBI-1065845 on the Pharmacokinetics of Ethinyl Estradiol Levonorgestrel or Midazolam in Healthy Adults (ASCP 2023) - P2 | "Study funded by Neurocrine Biosciences, Inc. Learning Objectives To understand potential drug-drug interaction of NBI-1065845 with oral contraceptives To understand potential drug-drug interaction of NBI-1065845 with midazolam"

Clinical • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SAVITRI: Study to Assess the Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P2 | N=155 | Recruiting | Sponsor: Neurocrine Biosciences | Trial completion date: Oct 2023 ➔ Jan 2024

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

Role of the AMPA receptor in antidepressant effects of ketamine and potential of AMPA receptor potentiators as a novel antidepressant. (PubMed, Neuropharmacology) - "Accumulating evidence from preclinical studies has shown that the antidepressant effects of ketamine are dependent on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) activation, which triggers activation of the mechanistic target of rapamycin pathway and brain-derived neurotrophic factor release. We further review the in vitro and in vivo profiles of TAK-653, including its procognitive and antidepressant-like effects, as well as its safety profile, in comparison with known AMPA-R potentiators with agonistic activity and AMPA, an AMPA-R agonist. The low agnostic activity of TAK-653 may overcome limitations of known AMPA-R potentiators."

Journal • Review • CNS Disorders • Depression • Epilepsy • Psychiatry • BDNF

Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers. (PubMed, Transl Psychiatry) - "TAK-653 6 mg improved AT (%) (1.68 [0.51, 2.84], P = 0.02) and increased SPV (degrees/s) (15.40 [1.91, 28.90], P = 0.06) and SP (%) (2.32 [0.37, 4.27], P = 0.05). Based on these findings it can be concluded that TAK-653 demonstrated a psychostimulant-like pharmacodynamic profile on the NeuroCart consistent with previously reported increase of cortical excitability following Transcranial Magnetic Stimulation (TMS) of the human motor cortex."

Clinical • Journal • CNS Disorders • Depression • Immunology • Major Depressive Disorder • Mood Disorders • Psychiatry

SAVITRI: Study to Assess the Efficacy and Safety of Adjunctive NBI-1065845 in Adults With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P2; N=212; Recruiting; Sponsor: Neurocrine Biosciences

New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats. (PubMed, Pharmacol Biochem Behav) - "Unlike ketamine, however, TAK-653 did not induce a hyperlocomotor response in rats, which is a behavioral index associated with psychotomimetic side-effects in humans. TAK-653 may be a promising drug for the treatment of major depressive disorders including TRD with the potential for an improved safety profile compared with ketamine."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement. (PubMed, Sci Rep) - "Importantly, TAK-653 had a wide safety margin against convulsion; TAK-653 showed a 419-fold (plasma C) and 1017-fold (AUC ) margin in rats. These findings provide insight into a therapeutically important aspect of AMPA-R potentiation."

Journal • CNS Disorders • Epilepsy

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation. (PubMed, Transl Psychiatry) - "TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators."

Biomarker • Journal • CNS Disorders • Depression • Immunology • Major Depressive Disorder • Mood Disorders • Psychiatry

Neurocrine Biosciences Provides Preliminary Fourth Quarter and Full-Year 2020 Net Product Sales Results and 2021 Program Milestones (PRNewswire) - "Neurocrine Biosciences, Inc....today provided an update on...key commercial and clinical development milestones for 2021. Kevin Gorman, Chief Executive Officer of Neurocrine Biosciences, will discuss these updates as part of a webcast presentation at the 39th Annual J.P. Morgan Healthcare Conference to be held virtually on Monday, January 11 at 2:00 p.m. Eastern Time...2021 Expected Milestones and Key Activities: NBI-1065845: Treatment Resistant Depression: Initiate Phase II; NBI-1065846: Anhedonia in Depression; Initiate Phase II."

New P2 trial • CNS Disorders • Depression

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Neurocrine Biosciences and Takeda Announce Collaboration to Develop and Commercialize Potential Therapies for Psychiatric Disorders (Businesswire) - "Neurocrine Biosciences, Inc....and Takeda Pharmaceutical Company Limited...today announced a strategic collaboration to develop and commercialize compounds in Takeda’s early-to-mid-stage psychiatry pipeline. Specifically, Takeda granted an exclusive license to Neurocrine Biosciences for seven pipeline programs, including three clinical stage assets for schizophrenia, treatment-resistant depression and anhedonia....Under the terms of the agreement, Neurocrine Biosciences will be responsible for developing and commercializing all pipeline compounds included in the collaboration."

Licensing / partnership • CNS Disorders • Depression • Schizophrenia

Functional Central Nervous System Effects of the Novel AMPA PAM (Positive Allosteric Modulator) TAK-653 Consistent with Finding of Increased Cortical Excitability Measured by TMS-MEP (SOBP 2020) - "Acute administration of the AMPA PAM TAK-653 demonstrated stimulatory effects such as increased visuomotor coordination and alertness, and improved sustained attention. These findings are consistent with the effects of an AMPA PAM to increase cortical excitability, as was previously demonstrated by the TMS-Motor Evoked Potential (MEP) results. Funding Source Funded Funding Source: Takeda Pharmaceuticals International"

Late-breaking abstract • CNS Disorders • Depression • Mood Disorders • Psychiatry