Trevi Therapeutics (NASDAQ:TRVI) used its fourth-quarter and year-end 2025 earnings call to outline next steps following what management described as a pivotal year driven by positive clinical data in two chronic cough programs. President and CEO Jennifer Good said 2025 marked a “major inflection point” for the company after favorable readouts from the CORAL trial in idiopathic pulmonary fibrosis (IPF)-related chronic cough and the RIVER trial in refractory chronic cough (RCC), which she said helped enable a capital raise and preparation for the next round of studies.
Good said that momentum continued into early 2026 with work culminating in a “positive end-of-phase II meeting” with the U.S. Food and Drug Administration (FDA) for the company’s IPF-related cough program. Trevi believes it now has a clear pathway toward registration trials and has been “moving aggressively” to initiate phase III development, according to management.
Phase III plan set for IPF-related chronic cough
Based on FDA input, Trevi plans to run two pivotal phase III trials in parallel, along with “remaining phase I clinical studies” to support an NDA submission. The first phase III trial is expected to begin in the second quarter of 2026 and will be a global 52-week study with a primary efficacy endpoint assessed after 24 weeks of fixed dosing. Trevi said it plans to enroll approximately 300 patients.
A second confirmatory phase III trial is expected to start in the second half of 2026. This global study will evaluate a primary efficacy endpoint at 12 weeks and is estimated to enroll approximately 130 patients. Management said the studies are “almost identical” aside from sample size and primary endpoint timing, reflecting FDA interest in a 24-week readout to support durability of effect in at least one trial.
Chief Development Officer James Cassella said the larger, 52-week trial is designed to support key secondary endpoints and an adequate safety database, while the smaller 12-week trial is intended to confirm primary efficacy outcomes and provide additional short-term safety data. Good noted that IPF-related chronic cough is a new indication for FDA and said the planned program is intended to generate robust safety and efficacy data.
Additional phase I work and regulatory considerations
During Q&A, Cassella provided details on phase I studies discussed with FDA. He said the agency asked Trevi to evaluate a potential drug-drug interaction (DDI) with nerandomilast, described as a newly approved anti-fibrotic agent, similar to prior DDI work the company conducted with pirfenidone and nintedanib. He also said Trevi will evaluate effects of enzyme inhibitors and inducers tied to the drug’s metabolism via cytochrome P450 2C9 and 2C19 pathways.
Cassella added that Trevi proposed—and FDA accepted—standard label-enabling studies such as renal impairment, hepatic impairment, and food effect. He said these studies are not expected to be rate-limiting and can be conducted in parallel with phase III.
On controlled substance considerations, Good said the end-of-phase II meeting included input from Controlled Substance Staff and remained focused on the company’s formulation rather than the underlying molecule, which she said is already unscheduled. She said Trevi’s data have not suggested a changed abuse profile and added that FDA discussion centered more on dependence than addiction. Cassella noted that dependence and withdrawal would be labeling considerations rather than scheduling issues.
Good also said Trevi plans to file an application for orphan drug designation for IPF-related chronic cough in 2026, while acknowledging uncertainty about whether the agency will grant it because of the broader implications if the therapy works in this difficult cough population.
Expanding into non-IPF ILD chronic cough
Beyond IPF, Trevi intends to request an FDA meeting and submit a protocol for a non-IPF interstitial lung disease (ILD)-related chronic cough program. Good said Trevi plans to propose an adaptive phase IIb design to confirm dose and power assumptions before rolling into a single pivotal phase III trial for approval. Management said it is planning for a supplemental NDA for this indication.
Trevi expects to hold the FDA meeting in the third quarter of 2026 and, if aligned, initiate the trial by year-end. Cassella said learnings from the IPF end-of-phase II meeting—such as study duration and endpoints—should carry over, and that the adaptive approach would help characterize effect size and variability in a “slightly different population” with additional comorbidities.
Asked about inclusion criteria, Cassella said the company does not plan a “basket” approach based on underlying ILD diagnoses. Instead, he said selection will be based on the amount of fibrosis and amount of cough, reflecting feedback from key opinion leaders.
RCC phase IIb dose-ranging planned; cash runway into 2028
For refractory chronic cough, Good said Trevi is planning a phase IIb parallel-arm dose-ranging trial with three doses and placebo. The protocol is being submitted to regulatory authorities and sites have been selected. The company plans to start the trial in the second quarter of 2026 and included a sample size re-estimation when 50% of patients complete the study. Good suggested the study will help determine whether dosing in RCC could be lower than, or similar to, doses being tested in IPF chronic cough, and said Trevi is exploring lower doses and a once-daily regimen.
On timing, Good said the company does not expect to complete the RCC trial in 2026 but is targeting the sample size re-estimation readout later in the year, with additional guidance to be provided when the study is formally initiated.
New CFO David Hastings said Trevi ended 2025 with approximately $188 million in cash, cash equivalents, and marketable securities, providing an expected runway into 2028. He said the runway is expected to fund top-line data from the company’s key trials, including phase IIb studies in RCC and non-IPF chronic cough and top-line data from the 12-week pivotal phase III IPF-related chronic cough trial. In response to analyst questions, Hastings confirmed that the runway as described does not cover the 24-week data from the longer IPF phase III trial, and Good said a key change is the FDA’s request for 52 weeks of controlled safety, which keeps the study blinded until completion.
Trevi also highlighted upcoming events, including an in-person Investor and Analyst Day in New York on May 7 and multiple accepted presentations and posters at the American Thoracic Society meeting, where the company expects to share new data and host an investor event.
About Trevi Therapeutics (NASDAQ:TRVI)
Trevi Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on the development of novel non-opioid therapies for the management of chronic and acute pain. The company leverages proprietary drug delivery platforms and targeted molecular approaches to address high unmet needs in cancer-related pain, chemotherapy-induced neuropathy and other severe pain conditions.
Its lead product candidate is a proprietary formulation of tetrodotoxin (TTX), a sodium-channel blocking agent being evaluated in early-stage clinical trials for moderate-to-severe pain associated with advanced cancer and peripheral neuropathy.
