Trevi Therapeutics (TRVI) Study Result summary

Study background and unmet need

• Chronic cough affects up to 85% of IPF patients, severely impacting quality of life and increasing risk of hospitalization and death, with no approved therapies available.

• Antifibrotic treatments do not improve cough symptoms in IPF, highlighting a major unmet need.

• Patient testimonials describe chronic cough in IPF as debilitating, causing physical exhaustion and social limitations.

• The US IPF population is estimated at 140,000, with 60-70% experiencing uncontrolled chronic cough.

• The CORAL phase 2b trial is the first parallel group study to show positive results for chronic cough in IPF.

Study design and methodology

• CORAL was a multi-center, randomized, double-blind, placebo-controlled, parallel, 4-arm dose-ranging Phase 2b trial of oral nalbuphine ER (Haduvio) in 165 IPF patients with chronic cough, mean age 70, mostly male, mean cough duration over four years.

• Doses tested: 27 mg BID, 54 mg BID, 108 mg BID, and placebo; patients required IPF diagnosis and chronic cough for at least 8 weeks with minimum severity.

• Study included a two-week titration and four-week fixed dose period, with cough measured at baseline, weeks 2, 4, and 6.

• Primary endpoint: relative change from baseline in 24-hour cough frequency at week six, measured objectively.

• Secondary endpoints: responder analysis, cough severity numerical rating scale, and patient-reported outcomes.

Efficacy results

• Statistically significant, dose-dependent reduction in cough frequency at all Haduvio doses: 108 mg BID (-60.2%), 54 mg BID (-53.4%), 27 mg BID (-47.9%) vs placebo (-16.9%), with a 43.3% placebo-adjusted reduction at the highest dose.

• Rapid onset of effect, with significant reduction observed by week two and sustained through week six.

• At week six, ≥50% reduction in cough frequency achieved by 65% (108 mg), 63% (54 mg), and 60% (27 mg) of Haduvio patients vs 19% for placebo.

• Patient-reported outcomes and secondary endpoints confirmed significant improvements in cough frequency and severity at higher doses.

• Cough reduction is clinically meaningful, with a 30% decrease considered significant for patients.