orvepitant (GW 823296) / NeRRe Therap - LARVOL DELTA

IPF COMFORT Study: A randomised, controlled trial evaluating the safety and efficacy of orvepitant as a treatment for chronic cough in IPF (ERS 2025) - "Both doses were well tolerated with no safety concerns. Orvepitant 30 mg once daily improved multiple patient-reported measures of cough burden in patients with IPF."

Clinical • Chronic Cough • Cough • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

IPF COMFORT: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=80 | Completed | Sponsor: Nerre Therapeutics Ltd. | Active, not recruiting ➔ Completed

Trial completion • Chronic Cough • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

IPF COMFORT: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=88 | Active, not recruiting | Sponsor: Nerre Therapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Cough • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

IPF COMFORT: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Nerre Therapeutics Ltd.

Trial completion date • Trial primary completion date • Chronic Cough • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

IPF COMFORT: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Nerre Therapeutics Ltd. | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • Chronic Cough • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

IPF COMFORT: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Nerre Therapeutics Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Cough • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Managed care considerations for the treatment of chronic cough. (PubMed, Am J Manag Care) - "New targeted therapies for refractory CC are currently under development, including the purinergic 2X3 receptor antagonists gefapixant, BLU-5937, and sivopixant (S-600918) and the neurokinin-1 receptor antagonist orvepitant. These targeted agents may have improved efficacy and safety profiles, helping fill unmet treatment needs. If approved, managed care organizations must develop formulary placement and utilization management criteria based on clinical guideline recommendations, expert opinion, and cost-effectiveness analyses to support the clinically appropriate use of these targeted therapies for best patient outcomes."

Journal • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Therpeutic Effect of Novel Antipsychotic Drugs Acting at Receptors of Neurotransmitters and Neuropeptides (NDS 2022) - "The combination of an NMDA receptor antagonist , for example ketamine with an M1 muscarinic cholinergic receptor antagonist, for example scopolamine, exert a rapid, long-lasting antidepressant effect. In preclinical studies, the antidepressant effect of orvepitant, an NK1 receptor antagonist, has been demonstrated: this antagonist reaches a complete antagonism of NK1 receptors...The superior therapeutic effect of antidepressant drugs like venlafaxine, a selective noradrenaline and serotonin reuptake inhibitor and bupropion, a selective dopamine and nordrenaline reuptake inhibitor and their adverse effects will be pointed out. Non-pharmacological measures to enhance the antidepressant effect will also be discussed."

CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Psychiatry

IPF COMFORT: Phase 2 Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With IPF (clinicaltrials.gov) - P2; N=88; Not yet recruiting; Sponsor: Nerre Therapeutics Ltd.

Clinical • New P2 trial • Chronic Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Pathophysiology of intractable chronic cough and new treatment development (WAC 2020) - "Gabapentin, amitriptyline Drugs that are effective against neuropathic French pain in addition to central nervous system diseases such as phosphorus and pregabalin Example Findings that respond to cough support the idea of treating cough as sensory neuropathy...Also substance P receptor neurokinin (NK)- The efficacy of 1 antagonist orvepitant was also recently reported (Smith et al. Chest 2019). In the lecture, the pathophysiology and treatment of intractable chronic cough We will also outline the latest findings."

Asthma • Gastroesophageal Reflux Disease • Immunology • Pain • Respiratory Diseases

Mass Balance Study of [14C]-Orvepitant Oral Solution in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Completed; Sponsor: Nerre Therapeutics Ltd.; Not yet recruiting ➔ Completed

Clinical • Trial completion

The Neurokinin-1 Receptor Antagonist Orvepitant is a Novel Antitussive Therapy for Chronic Refractory Cough: Results from a Phase 2 Pilot Study (VOLCANO-1). (PubMed, Chest) - P2 | "Orvepitant resulted in a significant, and sustained improvement in objective cough frequency, severity VAS, and QoL; appeared safe; and merits further clinical investigation."

Clinical • Journal • P2 data

Mass Balance Study of [14C]-Orvepitant Oral Solution in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Not yet recruiting; Sponsor: Nerre Therapeutics Ltd.

Clinical • New P1 trial

Therapeutic Effect of Novel Antidepressant Drugs Acting at Specific Receptors of Neurotransmitters and Neuropeptides. (PubMed, Curr Pharm Des) - "In clinical studies, the combination of an NMDA receptor antagonist with a M1 muscarinic cholinergic receptor antagonist should be investigated in-depth as well as the therapeutic effect of orvepitant. In clinical studies, the antidepressant effect of a triple reuptake inhibitor should be examined and compared to current antidepressant drugs."

Journal

Neurokinin-1 antagonist orvepitant for EGFRI-induced pruritus in patients with cancer: a randomised, placebo-controlled phase II trial. (PubMed, BMJ Open) - P2; "Orvepitant was safe and well tolerated. No difference in NRS score between the orvepitant and placebo groups was observed at the week 4 primary endpoint. A number of explanations for this outcome are possible."

Clinical • Journal • P2 data • EGFR

Late Breaking Abstract - The neurokinin-1 receptor antagonist orvepitant improves chronic cough symptoms: results from a Phase 2b trial (ERS 2019) - "These data support orvepitant’s further evaluation in CC."

Late-breaking abstract • P2b data

NK-1 Receptor Antagonists and Pruritus: Review of Current Literature. (PubMed, Dermatol Ther (Heidelb)) - "For this purpose, a systemic electronic literature search of the PubMed and CINAHL databases, Cochrane Library, and clinicaltrials.gov website was performed. Based on currently available data, it can be concluded that NK-1 inhibitors show significant antipruritic potential for treatment of chronic pruritus in different dermatological conditions, but further studies are needed to establish the best indications and dosage of these drugs."

Journal • Review