troriluzole (BHV-4157) / Biohaven - LARVOL DELTA

Withdrawal of applications (European Medicines Agency) - "An application for an initial marketing authorisation was withdrawn. Dazluma (troriluzole hydrochloride monohydrate) was intended for the treatment of spinocerebellar ataxia genotype 3 (SCA3), an inherited brain disorder that affects coordination and balance....An application to extend the therapeutic indication of Ngenla (somatrogon) in the treatment of adults with growth hormone deficiency was also withdrawn."

CHMP • Ataxia • Growth Hormone Deficiency (Adult)

A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Eudocia Quant Lee, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Glutamate Modulator (Troriluzole)...Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively. Myostatin (Taldefgrobep alfa): Expect FDA meeting to discuss SMA registrational path in 1H 2025. Initiate taldefgrobep Phase 2 study in obesity in 1H 2025. Continue advancing enrollment in proof of concept trial with BHV-2100 in acute migraine; data from the laser-evoked potential study expected in 1H 2025...Initiate BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025."

FDA event • New P2 trial • New P2/3 trial • P2 data • P3 data • Migraine • Muscular Atrophy • Obesity • Obsessive-Compulsive Disorder • Parkinson's Disease

Comparative Effectiveness of Troriluzole Versus Untreated Natural History Cohorts in Spinocerebellar Ataxia Leveraging Propensity Score Matching Methods (AAN 2025) - P, P3 | "Compelling and sustained treatment effects were observed out to 3 years when troriluzole-treated subjects were compared to 3 different matched untreated natural history cohorts, supporting that long-term daily dosing of troriluzole attenuates the progression of disease among SCA subjects."

HEOR • Ataxia • CNS Disorders • Movement Disorders

Troriluzole in Adult Participants With Spinocerebellar Ataxia (clinicaltrials.gov) - P3 | N=299 | Active, not recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | N=218 ➔ 299

Enrollment change • Ataxia • Movement Disorders

Biohaven Announces FDA Acceptance and Priority Review of Troriluzole New Drug Application for the Treatment of Spinocerebellar Ataxia (PRNewswire) - "Biohaven Ltd...announced that the US Food and Drug Administration (FDA) has accepted for review the Company's New Drug Application (NDA) for troriluzole for the treatment of adult patients with spinocerebellar ataxia (SCA) and has granted Priority Review....The FDA's decision regarding the NDA is expected within 6 months of filing (during 3Q2025). Based on FDA Priority Review timelines and if ultimately approved, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025....The NDA submission was based, in part, on positive topline results from Study BHV4157-206-RWE (NCT06529146)...The NDA also includes confirmatory and supportive data from Studies BHV4157-201 and BHV4157-206..."

FDA approval • FDA filing • Launch US • Priority review • Ataxia

Long-term Safety Study of Adjunctive Troriluzole in Subjects With Obsessive Compulsive Disorder (clinicaltrials.gov) - P3 | N=1200 | Enrolling by invitation | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Efficacy and Safety Study of Adjunctive Troriluzule in Obsessive Compulsive Disorder (clinicaltrials.gov) - P3 | N=700 | Active, not recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia. (PubMed, Neurol Ther) - P3 | "Psychometric evaluation showed that the FARS-ADL performed well on analyses examining the reliability and validity of the measure and can detect meaningful changes in patients with SCA, including those with SCA3."

Journal • Ataxia • Friedreich ataxia • Movement Disorders

Efficacy and Safety Study of Adjunctive Troriluzole in Obsessive Compulsive Disorder (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Comparative Effectiveness of Troriluzole versus Untreated Natural History Cohorts in Spinocerebellar Ataxia Leveraging Propensity Score Matching Methods (ICAR-Ataxia 2024) - No abstract available

HEOR • Late-breaking abstract • Ataxia • Movement Disorders

Comparison of Two Matching Methods to Assess Effectiveness of Troriluzole versus Untreated Natural History Cohort in Spinocerebellar Ataxia (ICAR-Ataxia 2024) - No abstract available

Ataxia • Movement Disorders

A Systematic Literature Review on the Efficacy of Pharmacological Interventions in Ataxia (ISPOR-EU 2024) - "Across these, idebenone and riluzole (2 studies each) were the most commonly assessed interventions, followed by one study each for amantadine hydrochloride, deferiprone, luvadaxistat, omaveloxolone, rovatirelin, and troriluzole. Limited therapeutic options are available for ataxia, often focusing on symptomatic management rather than addressing the underlying cause. This SLR underscores a notable gap in treatments that directly target ataxia and highlights the potential pharmacological treatments in treating ataxia or slowing its progression."

Clinical • Review • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders

Trial in Adult Subjects With Spinocerebellar Ataxia (clinicaltrials.gov) - P2/3 | N=141 | Completed | Sponsor: Biohaven Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Ataxia • Movement Disorders

Real-World Data Study of Troriluzole-Treated Patients With Spinocerebellar Ataxia (SCA) Compared to a Matched Natural History Control (clinicaltrials.gov) - P=N/A | N=909 | Active, not recruiting | Sponsor: Biohaven Therapeutics Ltd. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Ataxia • Movement Disorders

Troriluzole (BHV-4157) in Adult Participants With Obsessive Compulsive Disorder (clinicaltrials.gov) - P2/3 | N=426 | Active, not recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Sep 2024 ➔ Mar 2026

Trial completion date • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice. (PubMed, J Neurochem) - "Second, we sought to determine whether treatment with troriluzole, a novel 3rd generation tripeptide prodrug of the glutamate modulator riluzole, could reduce VGlut1 and glutamate release to restore cognitive deficits in 8-month-old 3xTg mice. Treatment with troriluzole reduced VGlut1 expression, decreased basal and evoked glutamate release, and restored cognitive deficits in 3xTg mice. Together, these findings suggest presynaptic alterations are early events in AD that represent potential targets for therapeutic intervention, and these results support the promise of glutamate-modulating drugs such as troriluzole in Alzheimer's disease."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • SLC2A1

A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: Eudocia Quant Lee, MD

New P1 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer? (PubMed, Expert Opin Drug Discov) - "The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients."

Journal • Review • Inflammation • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Real-World Data Study of Troriluzole-Treated Patients With Spinocerebellar Ataxia (SCA) Compared to a Matched Natural History Control (clinicaltrials.gov) - P=N/A | N=1000 | Enrolling by invitation | Sponsor: Biohaven Therapeutics Ltd.

New trial • Real-world • Real-world evidence • Ataxia • Movement Disorders

Psychometric Validation of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) in Patients With Spinocerebellar Ataxia. (PubMed, Cerebellum) - P3 | "Psychometric measurement properties and minimal change thresholds of the f-SARA were evaluated using data from a cohort of SCA subjects (recruited at Massachusetts General Hospital [MGH]; n = 33) and data from a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), including a subset of patients with the SCA3 genotype (n = 89)...Similar trends were observed in Study 206 all-SCA and SCA3 cohorts. The measurement properties of the f-SARA provide evidence of its psychometric validity, responsiveness, and suitability as a clinical outcome measure in patients with SCA, including those with SCA3."

Journal • Ataxia • Movement Disorders

Video-Based Kinematic Analysis of Movement Quality in a Phase 3 Clinical Trial of Troriluzole in Adults with Spinocerebellar Ataxia: A Post Hoc Analysis. (PubMed, Neurol Ther) - P3 | "Using this novel approach, troriluzole-treated subjects demonstrated improvement in gait as compared to placebo for the tandem walk. Machine learning applied to video-captured gait parameters can complement clinician-reported motor assessment in adults with SCA. The Pose Dispersion Index may enhance assessment in future research. TRIAL REGISTRATION-CLINICALTRIALS."

Journal • P3 data • Retrospective data • Video • Ataxia • Movement Disorders

Open Pilot Trial of BHV-4157 (clinicaltrials.gov) - P3 | N=24 | Active, not recruiting | Sponsor: University of California, Los Angeles | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Apr 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Ataxia • Movement Disorders

Troriluzole, a Novel Glutamate Modulating Agent, in Development for Obsessive-Compulsive Disorder (ASCP 2024) - "Troriluzole is designed to provide enhanced bioavailability, eliminate the need for fasting, enable once-daily dosing, reduce first pass metabolism, and minimize hepatotoxicity relative to its active metabolite, riluzole. A Phase 2 proof of concept study of troriluzole in OCD demonstrated treatment benefit, and patients with more severe OCD symptoms at baseline experienced larger treatment effects. These results informed the development of 2 ongoing Phase 3 clinical trials. These two Phase 3 clinical trials are evaluating troriluzole in a population with moderate-to-severe OCD symptoms despite standard of care therapy."

CNS Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Two Randomized, Double-Blind, Placebo-Controlled Trials of Troriluzole, a Novel Glutamate Modulating Agent, in Obsessive-Compulsive Disorder (ASCP 2024) - "Troriluzole is designed to provide enhanced bioavailability, eliminate the need for fasting, enable once-daily dosing, reduce first pass metabolism, and minimize hepatotoxicity relative to its active metabolite, riluzole. These two Phase 3 clinical trials are evaluating troriluzole in a population with moderate-to-severe OCD symptoms despite standard of care therapy. These results underscore the incomplete efficacy of available therapies which are also associated with sexual dysfunction, metabolic syndrome, and extrapyramidal symptoms. If troriluzole proves to be safe and efficacious, this will be the first novel mechanism of action in OCD in over 20 years and an important breakthrough for the millions of patients suffering from this disorder."

Clinical • CNS Disorders • Cognitive Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry