A Pipeline in a Product: Haduvio™
Trevi is developing the investigational therapy Haduvio™ (nalbuphine ER) in a range of indications for which patients have few treatment options. With its dual mechanism of action, acting as both an antagonist (blocker) to the mu opioid receptor and as an agonist (activator) to the kappa opioid receptor, Haduvio™ has the potential to significantly improve the quality of life of patients suffering from serious neurologically mediated conditions by targeting the central and peripheral nervous systems.
We are conducting a global clinical development program for Haduvio™.
Pruritus Associated with Prurigo Nodularis (PN)
Prurigo Nodularis is a chronic, intensely pruritic dermatological condition characterized by the presence of pruriginous lesions such as papules, nodules or plaques, which may be associated with excoriations and ulcerations.
In September 2018, we initiated our pivotal Phase 2b/3 PRISM (Pruritus Relief thru Itch-Scratch Modulation) clinical trial evaluating the safety and efficacy of Haduvio™ in patients with severe pruritus associated with PN.
The PRISM trial is a randomized, double-blind, placebo-controlled, parallel, two-arm, 14-week treatment study that is evaluating the safety and anti-pruritic efficacy of Haduvio™ 162 mg tablets in 360 patients at more than 60 sites in the United States and Europe.
Interested in the PRISM trial? Click: https://www.theprismstudy.com to take the short Pre-Qualifying questionnaire.
We are now enrolling patients in the U.S. (NCT number: NCT03497975) and in the EU.
Pruritus in Chronic Liver Disease
A common complication of chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC); patients develop severe whole-body itch, an intense, intractable, debilitating condition that significantly disrupts patients’ daily activities and sleep, and consequently impairs their quality of life.
A Phase 1b open label study is complete to determine the safety and pharmacokinetics of Haduvio™ in patients with moderate to severe chronic liver disease.
Uremic Pruritus (UP)
A common, disruptive pruritic condition principally experienced by an estimated 70% of patients undergoing hemodialysis; causes significant impairment in patients’ quality of life and increased mortality.
We are not actively developing Haduvio™ for uremic pruritus at this time based on our evaluation of the market dynamics, but may consider resuming development in the future.
Chronic Cough in Patients with Idiopathic Pulmonary Fibrosis (IPF)
IPF is a rare, chronic, progressive lung disease, characterized by scarring and thickening of lung tissue; most patients diagnosed with IPF suffer from a dry, non-productive chronic cough that interrupts their daily living and significantly contributes to poor quality of life.
We are conducting a Phase 2 clinical trial of Haduvio™ for chronic cough in patients with IPF. The Phase 2 trial is a randomized, double-blind, placebo controlled, two-treatment, two-period, crossover study designed to evaluate the efficacy, safety, tolerability and dosing of Haduvio™ for chronic cough in up to 56 patients with IPF in the United Kingdom.
Levodopa-induced Dyskinesia (LID) in Patients with Parkinson’s Disease
Involuntary movements that negatively impact patients’ lives; it is estimated that motor complications resulting from levodopa therapy affect about 400,000 patients with Parkinson’s disease in the United States, with dyskinesia occurring in approximately 150,000 patients.
Subject to discussions with the FDA and the submission of an IND for this indication, we intend to initiate a Phase 2 trial of Haduvio™ to evaluate the effect of Haduvio™ on LID in patients with Parkinson’s disease.
scientific and clinical
posters & publications
The Role of Kappa- and Mu- Opioid Receptors in Pruritus
as presented at Maui Derm for Dermatologists 2021
Modulation of the Mu and Kappa Opioid Axis for Treatment of Chronic Pruritus
as presented at Maui Derm for Dermatologists 2021
Prevalence of prurigo nodularis in the United States of America: A retrospective database analysis
Ständer et al., The American Academy of Dermatology (JAAD) International (2020)
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus
as presented at the 2020 Fall Clinical Dermatology Conference
Efficacy and Safety of Oral Nalbuphine Extended Release in Prurigo Nodularis: Results of a Phase 2, Randomized, Controlled Trial with an Open-Label Extension Phase
as presented at the 2020 Fall Clinical Dermatology Conference
Prevalence of Prurigo Nodularis in Poland
Reich and Ryczek, Acta Dermato Venereologica (2020)
Prevalence of Prurigo Nodularis in the United States: Findings of a Retrospective Database Analysis
as presented at the 2020 AAD Annual Meeting
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus
Mathur et al., American Journal of Nephrology (2017)
ER Tablets in Hemodialysis Patients with Severe Uremic Pruritus: Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
as presented at the National Kidney Foundation Spring 2016 Meeting.
Long-Term Effects of Nalbuphine ER Tablets in Hemodialysis Patients with Uremic Pruritus: A Multicenter Open-Label Trial
as presented at the National Kidney Foundation Spring 2016 Meeting.
Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus
Hawi, et al, BMC Nephrology (2015)
Pharmacokinetics of nalbuphine hydrochloride proof-of-concept study with pharmacokinetics demonstrating anti-pruritic activity of oral nalbuphine in hemodialysis patients with uremic pruritus
as presented at the 2014 Meeting of the Society for Investigative Dermatology.
Pharmacokinetics of Nalbuphine Hydrochloride Extended Release Tablets in Hemodialysis and Healthy Subjects following Multiple Escalating Oral Doses
as presented at the 2014 Meeting of the American College of Pharmacology.
Exploring Clinical and Pharmacological Effects of Nalbuphine HCl Oral Tablets in Hemodialysis Subjects with Pruritus
as presented at American Society of Nephrology’s 2014 Kidney Week.
Nalbuphine attenuates itch in the substance P-induced mouse model
as presented at 7th World Congress on Itch (2013).
