FDA Alignment Paves the Way for Trevi’s Parallel Phase 3 Trials in Chronic Cough Treatment
Trevi Therapeutics has reached a critical development milestone, announcing it has completed its End-of-Phase 2 meeting with the FDA and secured alignment on the next steps for its investigational therapy, Haduvio, in idiopathic pulmonary fibrosis (IPF)-related chronic cough. This provides the company with a clear regulatory path to initiate two pivotal Phase 3 clinical trials—an important move in a therapeutic area with no FDA-approved options.
Two Parallel Phase 3 Trials Planned for 2026—Major Clinical Milestones Ahead
With milestone guidance from the FDA, Trevi will run two randomized, double-blind, placebo-controlled Phase 3 trials. The first pivotal trial is anticipated to begin in Q2 2026 with about 300 patients over 52 weeks of fixed dosing (primary endpoint at 24 weeks). The second trial is targeted for the second half of 2026, enrolling approximately 130 patients for 12 weeks of fixed dosing. Both trials will test the efficacy of nalbuphine ER (54 mg BID) versus placebo, measuring the reduction in 24-hour cough frequency as the primary endpoint.
| Trial Name | Estimated Start | Planned Enrollment | Dosing Duration | Primary Endpoint |
|---|---|---|---|---|
| Phase 3 Trial #1 | Q2 2026 | ~300 Patients | 52 Weeks | Relative change in 24-hr cough frequency at 24 weeks |
| Phase 3 Trial #2 | H2 2026 | ~130 Patients | 12 Weeks | Relative change in 24-hr cough frequency |
Significant Unmet Need—Why the Program Matters to Patients
IPF-related chronic cough remains a burdensome condition for nearly 100,000 U.S. patients (about two-thirds of the 150,000 living with IPF), with some experiencing up to 1,500 coughs per day. The chronic, uncontrolled nature of this symptom is linked with worsened morbidity, faster disease progression, and reduced quality of life. With no FDA-approved therapies, Trevi’s program stands out as a hope for a meaningful advance in care.
Haduvio’s Unique Mechanism Is Central to Trevi’s Value Proposition
Haduvio (oral nalbuphine ER) is the first investigational therapy shown in trials to achieve statistically significant cough reduction in both IPF and refractory chronic cough populations. As a kappa agonist and mu antagonist (KAMA), it acts on opioid receptors centrally and peripherally, targeting the reflex arc implicated in chronic cough. Notably, nalbuphine ER is not scheduled under the U.S. Drug Enforcement Agency, potentially streamlining future commercialization, if approved.
Regulatory Alignment Reduces Risk Heading into Phase 3
Securing FDA agreement on clinical trial design and endpoints reduces regulatory uncertainty—a frequent stumbling block in rare disease programs. Parallel execution of two pivotal trials could also accelerate time to potential New Drug Application (NDA) submission, should both deliver positive results. Still, risks remain, as success in earlier trials does not guarantee Phase 3 efficacy, and the FDA must sign off on final protocols.
Key Next Steps for Investors and Stakeholders
Trevi’s execution over the next 12–24 months will be under watch. With both global trials set to launch in 2026, progress on manufacturing, site selection, and patient recruitment milestones will be worth tracking. The breadth of clinical data will be crucial for FDA review, and clarity on potential endpoints, safety, or interim analyses could provide additional milestones.
Bottom line: Gaining FDA alignment for two pivotal Phase 3 studies in IPF-related chronic cough marks a major advance in Trevi’s development timeline, laying the groundwork for a potential first-in-class therapy in an area where treatment options are lacking. Both patients and investors will be watching closely as Trevi enters this pivotal stage.
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