Trevi Therapeutics (NASDAQ:TRVI) said it began two clinical trials during the second quarter and plans to launch a third study in the third quarter as it advances nalbuphine ER, also known as Haduvio, for multiple chronic-cough indications.
President and Chief Executive Officer Jennifer Good said the company initiated the OCEAN-1 Phase III, 52-week study in patients with idiopathic pulmonary fibrosis, or IPF, related chronic cough, as well as the LAKE-2b trial in refractory chronic cough, or RCC. Trevi expects to initiate OCEAN-2, its second Phase III IPF-related chronic-cough trial, in the third quarter. The OCEAN-2 study is designed to run for 12 weeks.
Non-IPF ILD Program Seeks FDA Alignment
Trevi has requested a meeting with the Food and Drug Administration to discuss development of nalbuphine ER for chronic cough associated with non-IPF interstitial lung disease, or ILD. Good said the company expects to learn during August whether the agency has granted the meeting request.
If the meeting is granted, Trevi plans to submit a full protocol and briefing materials covering the next study and broader development plan for the indication. Chief Development Officer James Cassella said the company expects a prospective non-IPF ILD protocol to closely follow the OCEAN IPF program, including endpoints, while focusing discussions with the FDA on exclusion criteria and the route to a new drug application.
Cassella said key opinion leaders have characterized IPF and non-IPF ILD cough as similar in their underlying relationship to lung disease. Trevi intends to discuss what it views as the most efficient regulatory route to approval for non-IPF ILD-related chronic cough, though the final path remains subject to FDA feedback.
LAKE Study Re-estimation Expected in Fourth Quarter
Trevi expects to report results of a sample-size re-estimation, or SSRE, for the Phase IIb LAKE trial in RCC during the fourth quarter. The analysis will occur after 50% of participants have completed the study and will be conducted by an external, unblinded statistician.
The assessment is intended to confirm the study’s powering assumptions and adjust enrollment if needed. Cassella said the protocol allows for as much as a 50% increase in sample size and is designed to target 80% conditional power. He said a potential increase in enrollment would be a statistical adjustment rather than an indication of a clinical issue.
Management said a recent termination of a competing RCC program has not changed Trevi’s clinical approach or the assumptions underlying LAKE. Cassella said the company powered the trial using data from its own RIVER RCC study and the CORAL program in IPF-related chronic cough.
Good said the competitive development could offer some protection against uncertainty surrounding placebo response. She also said investigator interest in the RCC trial has been strong, with no competing program currently enrolling patients and a potentially available pool of participants previously involved in other chronic-cough studies.
Commercial Strategy Focuses on Specialists
Chief Commercial Officer Farrell Simon said Trevi continues to position itself as an IPF- and ILD-led company, with pulmonologists as its primary commercial audience. The company estimates that its initially targeted treatment-resistant RCC population represents about 1 million patients in the U.S.
Simon said the commercial strategy for RCC remains unchanged despite the recent competitor setback. Trevi intends to focus on patients with high unmet needs who have had chronic cough for more than a year and are treated by specialists. In practice, the company expects segmentation to rely more on measures such as cough severity than on cough counts.
Management said the eventual dose selected from the RCC Phase II study could affect its commercial options. Simon said a lower dose could potentially enable different market positioning, while a dose similar to that used in IPF and ILD would require attention to preserving specialty pricing and avoiding cannibalization of those indications.
Trevi launched an unbranded digital campaign during the second quarter to raise awareness of chronic cough’s disease burden among pulmonologists. Good said the campaign, which includes patient testimonials from IPF and non-IPF ILD populations, has reached more than 17,000 unique pulmonologists. The company plans to expand its outreach through digital efforts, medical meetings and patient-advocacy networks.
Financial Position and Upcoming Data
Chief Financial Officer David Hastings said Trevi ended the second quarter with approximately $319 million in cash, cash equivalents and marketable securities. The company maintained its prior cash-runway guidance, which extends into 2030.
The projected runway includes funding for the IPF-related chronic-cough program through potential FDA approval, Phase III development in non-IPF ILD-related chronic cough, the ongoing Phase IIb LAKE trial in RCC, and pre-commercial activities. It does not include the costs of a commercial launch of Haduvio or a Phase III trial in RCC.
Trevi also highlighted six presentations or posters accepted at the American Thoracic Society meeting, including Phase II findings involving breathlessness, cough bouts and outcomes across baseline cough-count levels. Good said the company’s Phase IIb CORAL study in IPF-related chronic cough, which was published in JAMA, was highlighted during an ATS clinical year-in-review session.
Looking ahead, Trevi expects FDA alignment on its non-IPF ILD program, 50% enrollment in LAKE-2b and the LAKE SSRE result during the second half of 2026. Management said OCEAN-2 is expected to produce topline results in the second half of 2027, followed by OCEAN-1 results in the first half of 2028. Good said Trevi does not intend to hold OCEAN-2 results until OCEAN-1 is complete.
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.
