Trevi Therapeutics Reveals Positive Phase 2a Results for Haduvio in Refractory Chronic Cough Trial

Trevi Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced promising results from its Phase 2a RIVER trial, evaluating Haduvio™ for the treatment of refractory chronic cough (RCC). Haduvio, an investigational therapy, achieved the primary endpoint by significantly reducing 24-hour cough frequency by 67% from baseline, with a placebo-adjusted change of 57% (p<0.0001). These results are notable as RCC currently lacks approved therapies in the United States, making this a significant development in addressing this challenging condition.

Jennifer Good, President and CEO of Trevi Therapeutics, expressed her satisfaction with the trial outcomes, noting the efficacy of Haduvio even at the lowest dose tested. The results underscore Haduvio's potential in treating neurological cough disorders, which have a substantial impact on patients' lives. Good emphasized that these findings, combined with previous successes in treating chronic cough in idiopathic pulmonary fibrosis (IPF) patients, further validate the drug's mechanism targeting cough reflex hypersensitivity both centrally and peripherally.

The RIVER trial, a randomized, double-blind study, assessed the efficacy, safety, and tolerability of Haduvio for RCC treatment. Participants in the trial underwent two treatment phases lasting 21 days each, separated by a 21-day washout period. Patients received escalating doses of Haduvio, and their cough frequency was monitored objectively. The trial's primary endpoint focused on the mean change in 24-hour cough frequency by the end of the treatment period.

Secondary analyses revealed consistent efficacy across various patient groups. For those with severe baseline cough frequency, Haduvio demonstrated a 66% reduction, while patients with moderate cough frequency saw a 68% reduction, both achieving statistical significance (p<0.0001). Additionally, 84% of Haduvio-treated patients experienced at least a 30% reduction in cough frequency compared to 29% in the placebo group. Improvements were evident as early as Day 7 for those receiving the lowest dosage, as measured by patient-reported outcomes and objective cough monitoring.

Professor Jacky Smith from the University of Manchester highlighted the significance of these results, particularly in addressing the physical and psychological challenges faced by RCC patients. The debilitating nature of RCC, with symptoms such as chest pain and urinary incontinence, calls for effective therapies to alleviate patient suffering.

Safety assessments of the trial were consistent with Haduvio's known profile from previous studies. Common adverse events included constipation, nausea, somnolence, headache, dizziness, and fatigue, with no serious treatment-emergent adverse events reported.

Trevi Therapeutics plans to advance the development of Haduvio based on these promising results, aiming to meet the unmet needs of chronic cough patients. Discussions with the FDA are anticipated to define the next steps, including initiating further studies upon receiving regulatory feedback. The company appreciates the contributions of patients and investigators in advancing clinical research for RCC.

Trevi Therapeutics specializes in developing therapies for chronic cough associated with IPF and RCC. Their investigational drug, Haduvio, utilizing a KAMA mechanism (kappa agonist and mu antagonist), targets cough hypersensitivity at the central and peripheral levels. As RCC significantly impacts patients' quality of life, Trevi's efforts in bringing Haduvio to market represent a crucial step towards offering effective relief.