8-K: Trevi Therapeutics Reports Highly Positive Phase 2b CORAL Trial Results for Haduvio in IPF Chronic Cough

Trevi Therapeutics, Inc. announced overwhelmingly positive topline results from its Phase 2b CORAL clinical trial of Haduvio for chronic cough in patients with idiopathic pulmonary fibrosis (IPF), demonstrating statistically significant reductions in cough frequency across all dose groups.

Summary

• Trevi Therapeutics announced positive topline results from its Phase 2b CORAL clinical trial of Haduvio (oral nalbuphine ER) for the treatment of chronic cough in patients with idiopathic pulmonary fibrosis (IPF) on June 2, 2025.
• The trial achieved its primary endpoint, showing statistically significant reductions in 24-hour cough frequency across all dose groups at Week 6.
• Reductions from Baseline in 24-hour cough frequency were 60.2% (p<0.0001) for the 108 mg BID dose, 53.4% (p<0.0001) for the 54 mg BID dose, and 47.9% (p<0.01) for the 27 mg BID dose, compared to a 16.9% reduction in the placebo group.
• Placebo-adjusted differences in cough frequency were -30.9% for 27 mg BID, -36.5% for 54 mg BID, and -43.3% for 108 mg BID.
• A rapid reduction in 24-hour cough frequency was observed at Week 2, the first time point measured.
• A 50% reduction in 24-hour cough frequency at Week 6 was achieved by 65% of patients on 108 mg BID Haduvio (p<0.001), 63% on 54 mg BID Haduvio (p<0.001), and 60% on 27 mg BID Haduvio (p<0.001), compared to 19% of placebo patients.
• Statistically significant improvements were seen in the cough-severity numerical rating scale (CS-NRS) for the 108 mg BID (mean reduction of 3.0 points, p<0.05) and 54 mg BID (mean reduction of 3.2 points, p<0.01) dose groups.
• The 108 mg BID and 54 mg BID dose groups also showed statistical significance (p<0.01) on the patient-reported E-RS: IPF Cough Subscale, with mean relative changes from Baseline of -42.4% and -43.1% respectively, compared to -23% for placebo.
• Discontinuation rates due to adverse events were similar between combined Haduvio groups (5.6%) and the placebo group (5.0%).
• The safety profile was consistent with previous trials, with common adverse events including nausea, vomiting, constipation, dizziness, headache, fatigue, somnolence, and dry mouth.
• Serious adverse events were reported for 1.6% of patients across all Haduvio doses combined, compared to 10.0% in the placebo group.

Sentiment

Score: 9

Explanation: The document reports overwhelmingly positive Phase 2b clinical trial results for Haduvio, meeting its primary endpoint with high statistical significance and demonstrating strong efficacy across multiple measures. The safety profile is favorable, and the company has outlined clear next steps for further development, significantly de-risking the program and indicating strong potential for future success.

Positives

• Haduvio achieved the primary endpoint of statistically significant reductions in 24-hour cough frequency across all dose groups (108 mg BID, 54 mg BID, and 27 mg BID) at Week 6.
• The highest dose (108 mg BID) demonstrated a substantial 60.2% reduction in cough frequency from Baseline, significantly outperforming placebo's 16.9% reduction.
• Statistically significant improvements were observed in key secondary endpoints, including the cough-severity numerical rating scale (CS-NRS) and the patient-reported E-RS: IPF Cough Subscale for the 108 mg BID and 54 mg BID dose groups.
• A rapid reduction in cough frequency was noted as early as Week 2, indicating a quick onset of action.
• A high percentage of patients (up to 65% on 108 mg BID) achieved a clinically meaningful 50% reduction in 24-hour cough frequency.
• The safety profile of Haduvio was generally consistent with its known profile from previous trials, with similar discontinuation rates due to adverse events compared to placebo.
• The rate of serious adverse events was significantly lower in the Haduvio combined groups (1.6%) compared to the placebo group (10.0%).

Negatives

• The 27 mg BID dose group did not achieve statistical significance on the cough-severity numerical rating scale (CS-NRS) (p=0.46) or the E-RS: IPF Cough Subscale (mean relative change of -31.6%).
• Common adverse events reported included nausea, vomiting, constipation, dizziness, headache, fatigue, somnolence, and dry mouth, which, while consistent with known profile, are still side effects.

Risks

• Uncertainties regarding the success, cost, and timing of the Company's product candidate development activities and clinical trials.
• The risk that positive data from a clinical trial may not necessarily be predictive of the results of later clinical trials in the same or a different indication.
• Uncertainties regarding the Company's ability to execute on its strategy.
• Uncertainties with respect to regulatory authorities' views as to the data from the Company's clinical trials and next steps in the development path for Haduvio in the United States and foreign countries.
• Uncertainties inherent in estimating the Company's cash runway, future expenses, and other financial results, including the Company's ability to fund future operations, including clinical trials.

Future Outlook

Trevi Therapeutics expects to request an end of Phase 2 meeting with the U.S. Food and Drug Administration in the second half of 2025 to align on the Company's Phase 3 program for Haduvio for chronic cough in patients with IPF. The Company also anticipates initiating a clinical trial of Haduvio for the treatment of chronic cough in patients with non-IPF interstitial lung disease in the second half of 2025, with topline results expected in the second half of 2026. Furthermore, a Phase 2b clinical trial in patients with refractory chronic cough is expected to commence in the first half of 2026.

Industry Context

This announcement is highly significant for the chronic cough and rare lung disease therapeutic landscape, particularly for patients suffering from idiopathic pulmonary fibrosis (IPF) who often experience debilitating chronic cough with limited effective treatment options. Positive Phase 2b results for Haduvio, demonstrating strong efficacy and a consistent safety profile, position it as a promising candidate in an underserved market. This could potentially establish a new standard of care for IPF-related chronic cough and expand into other interstitial lung diseases, addressing a substantial unmet medical need within the respiratory pharmaceutical sector.

Stakeholder Impact

• Shareholders: Highly positive impact due to successful clinical trial results, which significantly de-risk the drug's development and could lead to increased stock valuation.
• Patients (IPF Chronic Cough): Significant positive impact as Haduvio could offer a much-needed effective treatment option for a debilitating symptom with a favorable safety profile.
• Employees: Positive impact due to company progress, potential for future growth, and validation of research and development efforts.
• Regulatory Authorities: Will be engaged for discussions on the Phase 3 program, with positive Phase 2b data providing a strong basis for progression.

Next Steps

• Request an end of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the second half of 2025 to align on the Phase 3 program for Haduvio for chronic cough in IPF.
• Initiate a clinical trial of Haduvio for the treatment of chronic cough in patients with non-IPF interstitial lung disease in the second half of 2025.
• Announce topline results for the non-IPF interstitial lung disease trial in the second half of 2026.
• Initiate a Phase 2b clinical trial in patients with refractory chronic cough in the first half of 2026.

Key Dates

Recommendation

Keywords

Trevi Therapeutics, Haduvio, nalbuphine ER, chronic cough, idiopathic pulmonary fibrosis, IPF, clinical trial, Phase 2b, CORAL, pharmaceutical, biotechnology, drug development, respiratory disease, SEC filing, 8-K