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Trevi Therapeutics Updates on Haduvio Clinical Trials

Trevi Therapeutics, Inc. (Nasdaq: TRVI), a clinical-stage biopharmaceutical company, recently provided exciting updates regarding its investigational therapy, Haduvio™ (oral nalbuphine ER), aimed at treating chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC). This announcement was made during the American Thoracic Society's 2025 International Conference, marking a significant moment for the company as they move forward in their clinical development.

Overview of the Phase 2a RIVER Trial

The Phase 2a RIVER trial was a randomized, double-blind, placebo-controlled crossover study designed with the primary goal of evaluating the efficacy, safety, and overall tolerability of Haduvio in patients suffering from RCC. The trial involved 66 patients and spanned over several treatment periods. Each phase consisted of 21 days of treatment followed by a 21-day washout period, allowing researchers to conduct a thorough analysis of the drug's impact on cough frequency.

In March 2025, Trevi announced that Haduvio achieved a significant primary endpoint, showcasing a reduction in the objective 24-hour cough frequency by 67% from the baseline and an impressive 57% on a placebo-adjusted basis (p<0.0001). These results prompted anticipation for further detailed analyses, which were subsequently revealed.

Additional Findings and Key Insights

1. Responder Analyses: The supplemental analyses presented at the conference elaborated on the responder criteria for cough frequency reduction at various thresholds (30%, 50%, and 75%). The data indicated that patients taking Haduvio exhibited statistically significant improvements across all dose ranges.

2. Leicester Cough Questionnaire Improvements: Participants using Haduvio noted substantial enhancements in the patient-reported Leicester Cough Questionnaire by Day 21 (108 mg BID), with statistical significance achieved (p<0.0001).

3. Treatment Design Insights: The crossover design showed no significant treatment period effects for the primary efficacy analysis concerning relative change from baseline in 24-hour cough frequency, which reinforces the stability of the findings.

4. Adverse Events Overview: Similar to earlier trials, side effects were more prevalent during the initial exposure to Haduvio, particularly at lower dosages. The frequency of side effects diminished with prolonged treatment over time, even as the dosage was increased.

5. Discontinuations and Risks: Most discontinuations occurred within the initial two weeks of Haduvio dosing and were primarily attributed to adverse events linked to the central nervous system and gastrointestinal issues.

The Future for Haduvio and Trevi Therapeutics

James Cassella, Ph.D., Chief Development Officer at Trevi Therapeutics, expressed optimism regarding the ongoing evaluations of the Phase 2a RIVER trial results. The initial data underscore the efficacy and consistent performance of nalbuphine ER in managing chronic cough symptoms. The company now looks ahead to the outcomes from their Phase 2b trial involving IPF patients with chronic cough, aiming to solidify the developmental path for both indications.

The Burden of Refractory Chronic Cough

RCC is classified as a debilitating condition with no approved therapies currently available in the U.S. It is characterized by persistent coughing lasting more than eight weeks, despite treatment for underlying conditions. Affecting approximately 2-3 million patients in the U.S., it often involves increased cough reflex sensitivity, yielding significant social and economic impacts on patients' lives, including sleep disturbance and potential urinary complications.

Trevi Therapeutics’ Commitment

In continuing their dedication to addressing chronic cough, Trevi Therapeutics aims to position Haduvio as a viable treatment alternative. Currently, Haduvio is poised to be the first investigational therapy demonstrating a statistically significant reduction in cough frequency for both IPF and RCC patients. With its unique mechanism of action as a kappa agonist and mu antagonist, Haduvio targets opioid receptors that are critical for cough control.

As Trevi progresses with their clinical evaluations, they remain committed to providing comprehensive updates to stakeholders. The advancements observed in the Phase 2a RIVER trial mark a crucial step towards meeting the needs of patients suffering from chronic cough worldwide.

For more information about Trevi Therapeutics and their innovative treatments, visit their official website at TreviTherapeutics.com and follow their updates on social media platforms.