Trevi Therapeutics Phase 2a RIVER Trial Showed that Haduvio Significantly Reduces RCC

March 10, 2025

DENVER, Colo., Mar 10, 2025 (247marketnews.com)- Trevi Therapeutics (NASDAD: TRVI) reported positive topline results from its Phase 2a RIVER trial evaluating Haduvio in Refractory Chronic Cough (RCC) patients. In this study involving 66 participants, Haduvio achieved a resounding success by meeting its primary endpoint, demonstrating a statistically significant reduction in 24-hour cough frequency of 67% from baseline and a 57% placebo-adjusted improvement, with a p-value of less than 0.0001. This marks a historic milestone as Haduvio becomes the first and only therapy to deliver statistically significant cough reduction across both RCC and IPF patient populations.

Jennifer Good , Trevi’s President and CEO, commented, “I am happy to share these robust positive results from our Phase 2a RIVER trial in refractory chronic cough which has been a difficult-to-treat indication with no approved therapies in the U.S. The RIVER trial demonstrated that Haduvio was highly effective, and worked quickly at the lowest dose tested across a broad range of cough counts. These results, coupled with our existing IPF chronic cough results, are further evidence of the effectiveness of Haduvio’s central and peripheral KAMA mechanism in treating these difficult neurological cough conditions which are so disruptive to patients’ lives.”

The Phase 2a Refractory Chronic Cough Improvement Via Nalbuphine ER (RIVER) trial was a randomized, double-blind, placebo-controlled crossover study aimed at assessing the efficacy, safety, and tolerability of Haduvio in RCC patients. The trial spanned two 21-day treatment periods, separated by a 21-day washout phase. During the Haduvio treatment arm, patients underwent dose titration starting at 27 mg twice daily (BID), escalating to 54 mg BID, and culminating at 108 mg BID, with objective cough monitoring and additional assessments conducted at each stage. The primary endpoint measured the mean change in 24-hour cough frequency at Day 21, as captured by an objective cough monitor, across the full analysis set (FAS) population—defined as all patients receiving at least one dose of the study drug and having cough data at both baseline and Day 21 for at least one treatment period. At the 108 mg BID dose, Haduvio reduced cough frequency by 67%, compared to a modest 10% reduction with placebo, yielding a 57% difference that underscored its profound efficacy (p<0.0001).

James Cassella, Ph.D., Trevi’s Chief Development Officer, stated, “The results from the RIVER trial were highly statistically significant with consistent outcomes across the primary and analyzed secondary endpoints as well as for patients with moderate or severe baseline cough frequency. We look forward to advancing development of nalbuphine ER in the hopes of providing relief for the significant unmet need for these chronic cough patients. Based on these results, we plan to discuss next steps with the FDA and anticipate initiating the next study after we receive their input. Thank you to all the patients and investigators who contributed to our trials and continue to advance clinical research to find a treatment for chronic cough.”

Beyond the primary endpoint, Haduvio showcased consistent results across additional measures. In patients with severe cough, defined as 20 or more coughs per hour, it achieved a 66% reduction in 24-hour cough frequency (p<0.0001), while those with moderate cough, ranging from 10 to 19 coughs per hour, experienced a 68% decrease (p<0.0001), proving its effectiveness across varying severity levels. 84% of patients on Haduvio saw at least a 30% reduction in cough frequency from baseline, compared to just 29% on placebo—a 55% difference that further validated its impact (p<0.0001). Relief came swiftly, with significant reductions in cough frequency observable as early as Day 7 at the 27 mg BID dose (p<0.0001). Patient-reported outcomes echoed these findings, with statistically significant improvements in the Cough Severity Visual Analog Scale and Patient-Reported Cough Frequency emerging by Day 7 at the lowest dose, reinforcing the drug’s rapid and meaningful effect.

Jacky Smith, Professor of Respiratory Medicine at the University of Manchester, added, “I am excited to see the positive results from the Phase 2a RIVER trial and the potential role nalbuphine ER could have in therapy for RCC patients. RCC significantly impacts patients’ lives both physically and psychologically, resulting in chest pain, urinary incontinence, depression, exhaustion, dizziness and much more. Therapies are desperately needed as patients continue to suffer from this debilitating disease.”

The safety profile of Haduvio remained consistent with prior trials, presenting no surprises. The most commonly reported adverse events included constipation, nausea, somnolence, headache, dizziness, and fatigue, but notably, no treatment-emergent serious adverse events occurred, affirming its tolerability. These results build on Haduvio’s established track record, positioning it as a promising therapy for a condition that affects millions worldwide with no approved treatments.

Trevi Therapeutics will host a conference call and webcast today at 8:30 a.m. ET, featuring insights from Professor Smith.

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