Trevi Therapeutics Completes Phase 2a RIVER Trial Enrollment for Refractory Chronic Cough

Trevi Therapeutics, Inc., a clinical-stage biopharmaceutical firm based in New Haven, Connecticut, has announced the completion of patient enrollment for its Phase 2a trial, dubbed RIVER, aimed at treating Refractory Chronic Cough (RCC). Trevi, listed on Nasdaq under the symbol TRVI, is developing an investigational therapy, Haduvio™ (oral nalbuphine ER), for chronic cough conditions, including those stemming from idiopathic pulmonary fibrosis (IPF) and RCC. The company has indicated that the topline results from this trial are anticipated to be available in the first quarter of 2025.

Jennifer Good, President and CEO of Trevi Therapeutics, expressed satisfaction with the completion of the enrollment phase for the RIVER trial, emphasizing the significant unmet need for effective RCC treatments. She pointed out that RCC affects around 2-3 million adults in the U.S. and currently lacks approved treatment options, underlining the importance of developing new therapies to address cough hypersensitivity. Good added that the company eagerly anticipates the topline results early next year, hoping to build on the positive outcomes previously observed in chronic cough studies related to IPF.

The Phase 2a RIVER trial is a rigorous study designed to assess the efficacy, safety, tolerability, and optimal dosing of Haduvio for RCC treatment. Conducted across various sites in the United Kingdom and Canada, this randomized, double-blind, placebo-controlled, crossover study involves two treatment periods. The primary endpoint focuses on the mean change in 24-hour cough frequency within the overall patient population, using an objective cough monitoring system. Participants are divided into two subgroups based on their cough frequency: those with 10-19 coughs per hour (moderate frequency) and those with 20 or more coughs per hour (high frequency). The study also investigates secondary endpoints, which include patient-reported outcomes regarding cough frequency and severity. Approximately 60 adult patients are enrolled in this trial.

RCC is characterized by a persistent cough lasting more than eight weeks that does not respond to treatments for underlying conditions, such as asthma, gastroesophageal reflux disease, non-asthmatic eosinophilic bronchitis, or upper airway cough syndrome. In cases where no underlying condition is identified, the cough persists due to hypersensitivity in the cough reflex pathway, affecting both central and peripheral nerves. RCC significantly impacts the quality of life, leading to complications like urinary incontinence, sleep disturbances, and social embarrassment, which impose substantial social and economic burdens on patients and their surroundings.

Trevi Therapeutics is committed to advancing Haduvio, which acts on opioid receptors, specifically as a kappa agonist and a mu antagonist (KAMA), playing a crucial role in controlling cough hypersensitivity. Notably, nalbuphine, the active ingredient in Haduvio, is not classified as a controlled substance by the U.S. Drug Enforcement Agency.

Chronic cough, particularly in IPF patients, is a major concern as it can lead to disease progression, increased mortality risk, and the potential need for lung transplants. Existing treatment options are insufficient, and there are no approved therapies for chronic cough in IPF or RCC in the U.S. Given that chronic cough affects up to 10% of the adult population, Haduvio's potential to treat moderate to severe RCC offers new hope for patients.

Trevi Therapeutics aims to establish Haduvio as the trade name for oral nalbuphine ER, though its safety and efficacy have yet to be thoroughly evaluated by regulatory authorities.