ralmitaront (RG7906) / Roche - LARVOL DELTA

18F-Dihydroxyphenylalanine (DOPA) Positron Emission Tomography (PET) Study to Explore Dopamine Synthesis Capacity in the Whole Striatum After 2 Weeks of Treatment With Ralmitaront or Placebo in Participants With Schizophrenia (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Hoffmann-La Roche

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

Trace amine-associated receptor 1 agonists for the treatment of negative symptoms of schizophrenia: a review (ECNP 2024) - "Ulotaront (SEP-363856) and ralmitaront (RO6889450) are two TAAR1 agonists in clinical trials. Based on data from preclinical and clinical trials, TAAR1 agonists may be beneficial in reducing negative symptoms of schizophrenia. Placebo-controlled studies focusing on negative symptoms in appropriate patient populations are important to determine the place of ulotaront in the future treatment of schizophrenia."

Review • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Development of novel selective morpholine trace amine-associated receptor 1 partial agonists with promising preclinical effects related to neuropsychiatric disorders and well tolerated in healthy volunteers (Neuroscience 2023) - "TAAR1 agonists from a previous amino oxazolines series have been broadly studied preclinically (e.g. RO5263397, RO5256390, RO5203648) and in clinic (e.g. RO5263397)...We developed two selective partial agonists of TAAR1 (RO6889450 and RO6799477) and tested them extensively in nonclinical models predictive of antipsychotic, stress-response modulating and anti-addictive properties...Both compounds also showed a potentiation of the effect of olanzapine on PCP-induced hyperlocomotion in mice and a partial reversal of cocaïne-induced facilitation in intracranial self-stimulation threshold in rats...Both molecules have been investigated in Phase I single ascending dose (SAD) and multiple ascending dose (MAD) studies conducted in healthy volunteers to evaluate the safety, tolerability, PK, and pharmacodynamics. Based on its unique behavioral profile TAAR1 activation could represent a novel therapeutic option for neuropsychiatric disorders, including schizophrenia and..."

Preclinical • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2 | N=287 | Completed | Sponsor: Hoffmann-La Roche | Terminated ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450) - Two TAAR1 Agonist Candidate Antipsychotics. (PubMed, Int J Neuropsychopharmacol) - "Compared to ulotaront, ralmitaront shows lower efficacy and slower kinetics at TAAR1, and lacks efficacy at 5-HT1AR. These data may be relevant to understanding differences in clinical profiles of these two compounds."

Journal • Preclinical • CNS Disorders

A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2 | N=128 | Terminated | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2023 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Mar 2023; This study was discontinued due to an interim analysis which indicated that ralmitaront was unlikely to meet its primary endpoint.

Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Psychiatry • Schizophrenia

A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2 | N=128 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=247 ➔ 128

Enrollment change • Enrollment closed • CNS Disorders • Psychiatry • Schizophrenia

A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2 | N=247 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2023 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2 | N=286 | Terminated | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2023 ➔ May 2022 | Recruiting ➔ Terminated; In a preliminary analysis, the primary endpoint was negative, and ongoing portions of the study have therefore been discontinued.

Trial completion date • Trial termination • CNS Disorders • Psychiatry • Schizophrenia

Existing and emerging pharmacological approaches to the treatment of mania: A critical overview. (PubMed, Transl Psychiatry) - "Results show limited novel or ongoing research on agents acting as mood stabilizers (Ebselen, Valnoctamide and Eslicarbazepine did not reach statistical significance in demonstrating antimanic efficacy). As for the emerging experimental antipsychotic, some of them (including KarXT, SEP-363856, RO6889450, ALKS3831) have demonstrated good antipsychotic efficacy and a favorable safety profile, but little is known about their use in patients with bipolar disorder and specifically designed trials are needed. Lastly, some benefits for the treatment of mania could be expected to come in the next future from non-mood stabilizers/non-antipsychotic agents (especially PKC inhibitors like Endoxifen): long-term trials are needed to confirm positive results in terms of long-term efficacy and safety."

Journal • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2 | N=308 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Apr 2023 ➔ Jul 2022

Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2 | N=247 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2022 ➔ May 2023 | Trial primary completion date: Dec 2022 ➔ May 2023

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics: Current Status of Research and Future Directions. (PubMed, CNS Drugs) - "Topics include an overview of TAAR-1 physiology and pathophysiology in schizophrenia, interaction with other neurotransmitter systems, including the dopaminergic, glutamatergic and serotonergic system, and finally, a review of investigational TAAR-1 compounds that have reached Phase II clinical studies in schizophrenia: SEP-363856 (ulotaront) and RO6889450 (ralmitaront). An ongoing study of ralmitaront will assess specific efficacy in patients with persistent negative symptoms. If trials of TAAR-1 modulators, and other novel-mechanism targets for schizophrenia that are under active study, continue to show positive results, the definition of an antipsychotic may need to be expanded beyond the DR target in the near future."

Journal • CNS Disorders • Psychiatry • Schizophrenia

A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2; N=247; Recruiting; Sponsor: Hoffmann-La Roche; N=500 ➔ 247; Trial completion date: Jun 2022 ➔ Dec 2022; Trial primary completion date: Jun 2022 ➔ Dec 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2; N=308; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Sep 2022 ➔ Apr 2023; Trial primary completion date: Sep 2022 ➔ Apr 2023

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Trial of the Efficacy and the Safety of RO6889450 vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2; N=308; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

A Trial of the Efficacy and the Safety of RO6889450 vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (clinicaltrials.gov) - P2; N=308; Not yet recruiting; Sponsor: Hoffmann-La Roche

Clinical • New P2 trial • CNS Disorders • Psychiatry • Schizophrenia

Chugai Pharmaceutical : CONSOLIDATED FINANCIAL STATEMENTS(IFRS)(Non-Audited)(for the second quarter of the fiscal year 2020) (Market Screener) - "We started global Phase II study for RG7906 for the treatment of schizophrenia in February 2020."

Trial status • CNS Disorders • Schizophrenia

A Study to Assess the Effects of RO6889450 in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2; N=500; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Jul 2020 ➔ Jun 2022; Trial primary completion date: Jul 2020 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Schizophrenia

A Study to Assess the Effects of RO6889450 in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (clinicaltrials.gov) - P2; N=500; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • CNS Disorders • Schizophrenia