Trevi Therapeutics has secured end-of-Phase 2 alignment with FDA for Haduvio (oral nalbuphine ER) in idiopathic pulmonary fibrosis (IPF)-related chronic cough and will run two Phase 3 trials in parallel starting in the second quarter and second half of 2026. The first study will enroll about 300 patients with a 24-week primary endpoint within a 52-week fixed-dosing period; the second will enroll about 130 patients with a 12-week primary endpoint. Both will use the relative change from baseline in 24-hour cough frequency measured by objective cough monitors as the primary endpoint. The company is also initiating a Phase 2b trial in refractory chronic cough this quarter and plans an adaptive Phase 2b study in non-IPF interstitial lung disease in the second half of 2026. Positive Phase 2b results in IPF-related cough were published in JAMA in January, and Trevi closed 2025 with $188.3 million in cash and securities, guiding runway into 2028.
The decision to advance two pivotal studies in parallel signals an aggressive bid to define the post-P2X3 chronic cough landscape with a mechanistically distinct option. It compresses timelines and could establish category leadership in IPF-associated cough, but it concentrates execution risk into a narrow window of site activation, device-enabled endpoint logistics, and sustained recruitment in a rare disease population. For a small-cap with a long cash runway, this is a calculated attempt to convert scientific momentum and regulatory clarity into market advantage before larger competitors set the terms of evidence and access.
The stakes are high for patients and pulmonologists who have few effective tools for the disabling cough that accompanies fibrotic lung disease. Objective cough frequency is a regulator-preferred endpoint and a practical readout for commercial discussions, but payers will ultimately look for validated links to quality of life, function, and potentially downstream outcomes such as exacerbations or hospitalizations. Haduvio’s kappa agonist/mu antagonist profile differentiates it from P2X3 antagonists often limited by taste disturbance, while its lack of DEA scheduling may ease prescribing and distribution. Long-term safety, CNS tolerability, and adherence under chronic use will be closely watched, and the 52-week safety arc in one pivotal trial is an important de-risking component for regulators and formularies.
The competitive picture in chronic cough is in flux. After a mixed regulatory path for the P2X3 class, the field’s center of gravity has shifted toward more selective agents and diversified mechanisms. GSK’s camlipixant is progressing in Phase 3 for refractory chronic cough, and other programs continue to test the boundaries of what cough frequency alone can unlock with FDA. Trevi’s focus on IPF- and ILD-related cough carves out a specialist-led segment where symptom control may also support adherence to background antifibrotics, offering a narrative that could resonate with both clinicians and payers. The JAMA publication confers peer-reviewed credibility at a moment when evidence quality is a key differentiator for partnering and market access.
For Commercial and Medical Affairs teams, the near-term priorities are clear: build a payer-ready value story that extends beyond cough counts, invest in pragmatic real-world evidence infrastructure to capture patient-reported outcomes and healthcare utilization, and ready sites and HCPs for standardized cough monitoring workflows at scale. With a balance sheet that can support parallel pivotal execution, Trevi has bought time to prove that symptomatic relief in a high-burden niche can translate into durable market access. The question now is whether the company can turn objective cough reductions into outcomes that regulators and payers view as materially meaningful before P2X3-based incumbents reset expectations in refractory cough.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
