rodatristat ethyl (RVT-1201) / Sumitomo Pharma - LARVOL DELTA

Important negative trials in pulmonary hypertension. (PubMed, Curr Opin Pulm Med) - "This article provides an overview of the key learning points from these studies and reinforces the importance of the publication of all trials, irrespective of outcome, so that we can learn from negative studies and prioritize promising therapies and treatment pathways."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Peak Steps Decrease After Treatment With Rodatristat Ethyl in Pulmonary Arterial Hypertension (ATS 2025) - "ConclusionActigraphy demonstrated changes within and between groups, while 6-minute walk distance was unchanged. Peak Steps is likely a better measurement of capacity for activity (influenced more by physiology and less by behavior) than daily summary metrics; it was the only metric to show between group and within group changes."

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial. (PubMed, Lancet Respir Med) - P2 | "Our results indicate that reducing peripheral serotonin concentrations via rodatristat ethyl has a negative effect on pulmonary haemodynamics and cardiac function in patients with pulmonary arterial hypertension. This finding suggests that manipulating this pathway might not be a suitable option for pulmonary arterial hypertension therapy."

Journal • P2b data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Thorough QT Study to Evaluate the Effect of Rodatristat Ethyl, Rodatristat and Its Major Metabolites on the Heart (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: Altavant Sciences GmbH | Recruiting ➔ Completed | N=64 ➔ 27 | Trial completion date: Nov 2023 ➔ Jul 2023

Enrollment change • Trial completion • Trial completion date

Rodatristat ethyl: peripheral serotonin targeting with low risk for impacting mood supportive of ELEVATE 2, a Phase IIb clinical study for pulmonary arterial hypertension (ERS 2023) - "RE is predicted to have low risk for impacting brain 5HT consistent with no changes in mood or suicidal ideation in healthy subjects.; Physiology; Respiratory intensive care; Epidemiology; General respiratory patient care; Public health; Pulmonary function testing"

Clinical • P2b data • Cardiovascular • CNS Disorders • Critical care • Hypertension • Mental Retardation • Mood Disorders • Pain • Psychiatry • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Suicidal Ideation

Rodatristat ethyl: characterization of reductions in peripheral serotonin supportive of ELEVATE 2, a Phase IIb clinical study for pulmonary arterial hypertension (ERS 2023) - "RE achieved dose-dependent reductions in serotonin synthesis in healthy subjects. A target ~40% reduction associated with efficacy in rat PAH models was achieved by day 7 for RE doses ≥300mg BID. Inhibition of 5HT biosynthesis was reversible.; Physiology; Respiratory intensive care; Epidemiology; General respiratory patient care; Public health; Pulmonary function testing"

Clinical • P2b data • Cardiovascular • Critical care • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2) (clinicaltrials.gov) - P2 | N=108 | Completed | Sponsor: Altavant Sciences GmbH | Recruiting ➔ Completed | Trial completion date: Feb 2023 ➔ Jun 2023 | Trial primary completion date: Feb 2023 ➔ Jun 2023

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Thorough QT Study to Evaluate the Effect of Rodatristat Ethyl, Rodatristat and Its Major Metabolites on the Heart (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Altavant Sciences GmbH

New P1 trial

Targeting Peripheral Serotonin for the Treatment of Pulmonary Arterial Hypertension (ATS 2023) - "Sponsored By Enzyvant Therapeutics Join Enzyvant Therapeutics in Mini Theater 1 on Sunday, May 21st from 12:30 – 1:00pm for an expert overview of the role of serotonin in the pathogenesis of pulmonary arterial hypertension and Phase IIb clinical trial for the investigation of rodatristat ethyl for the treatment of WHO Group 1 pulmonary arterial hypertension.Sponsored By Enzyvant Therapeutics Join Enzyvant Therapeutics in Mini Theater 1 on Sunday, May 21st from 12:30 – 1:00pm for an expert overview of the role of serotonin in the pathogenesis of pulmonary arterial hypertension and Phase IIb clinical trial for the investigation of rodatristat ethyl for the treatment of WHO Group 1 pulmonary arterial hypertension."

Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ELEVATE 2: Baseline Demographic Characteristics From the Phase IIB Study of the Efficacy and Safety of Two Doses of Rodatristat Ethyl When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (ATS 2023) - P2 | "In this first report of ELEVATE 2, demographic data are broadly consistent with previously reported PAH clinical trial patient populations. Patients were stratified based on mono, dual, or tripleSOC therapies which could include a continuous infusion of a prostanoid."

Clinical • P2b data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Single and Multiple Dose of Rodatristat Ethyl in Healthy Adult Subjects to Evaluate the Effect of Food and Safety (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Altavant Sciences GmbH | Recruiting ➔ Completed

Trial completion

A Single and Multiple Dose of Rodatristat Ethyl in Healthy Adult Subjects to Evaluate the Effect of Food and Safety (clinicaltrials.gov) - P1 | N=34 | Recruiting | Sponsor: Altavant Sciences GmbH

New P1 trial

Multiple-Ascending Dose in Japanese Patients Bridging Study (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Altavant Sciences GmbH | Recruiting ➔ Completed

Trial completion

Pharmacokinetics and Excretion of Oral [14C]-Rodatristat Ethyl (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: Altavant Sciences GmbH | Not yet recruiting ➔ Completed

Trial completion

A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2). (PubMed, Pulm Circ) - P2 | "The trial incorporates endpoints to generate essential clinical efficacy, safety, pharmacokinetic, and pharmacodynamic data needed to evaluate the ability of rodatristat ethyl to ameliorate PAH by halting or reversing pulmonary vascular remodeling through its unique mechanism of TPH1 inhibition. Herein we describe the experimental design highlighting the trial's unique features."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Rodatristat Ethyl Monotherapy and Combination with Ambrisentan Reverses Incidence of Vascular Occlusions to Baseline Normoxic Levels in the Rat SUGEN-Hypoxia Model of Pulmonary Arterial Hypertension (ATS 2022) - P2 | "Occlusions were measured following induction of PAH (subcutaneous injection of SUGEN SU5416 and hypoxia for 21 days) and after 28 days QD oral monotherapy with 50, 100 or 200mg/kg oral RODA, 10mg/kg ambrisentan, or combinations of 10mg/kg tadalafil and 10mg/kg ambrisentan, or 100mg/kg RODA and 10mg/kg ambrisentan (n≥11/active treatment). In conclusion, monotherapy with RODA reduced pulmonary vascular occlusions in the rat SuHx PAH model. Combination with ambrisentan suggested synergistic benefit reducing occlusions to near normal control levels with reduction in mPAP, together supportive of clinical benefit for RODA in treatment of PAH."

Monotherapy • Preclinical • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Multiple-Ascending Dose in Japanese Patients Bridging Study (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Altavant Sciences GmbH; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

"NOVEL MECHANISMS TARGETED BY DRUG TRIALS IN PULMONARY ARTERIAL HYPERTENSION". (PubMed, Chest) - "In this review, we will discuss the preclinical studies that led to prioritization of these mechanisms and will discuss recently completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells among others. We anticipate that the next generation of compounds will build upon the success of the current standard of care and improve clinical outcomes and quality of life of patients afflicted with PAH."

Journal • Review • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Multiple-Ascending Dose in Japanese Patients Bridging Study (clinicaltrials.gov) - P1; N=48; Not yet recruiting; Sponsor: Altavant Sciences GmbH

Clinical • New P1 trial

A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2) Estudio de Rodatristat de etilo en pacientes con hipertensión arterial pulmonar (ELEVATE 2) (clinicaltrialsregister.eu) - P2; N=90; Ongoing; Sponsor: Altavant Sciences GmbH

New P2 trial • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases

A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1) (clinicaltrials.gov) - P2a; N=3; Terminated; Sponsor: Altavant Sciences GmbH; N=36 ➔ 3; Recruiting ➔ Terminated; Inability to enroll

Clinical • Enrollment change • Trial termination