Trevi Therapeutics and the Emerging Opportunity in Chronic Cough Therapeutics

The biopharmaceutical landscape is witnessing a paradigm shift in the treatment of chronic cough, a condition long plagued by unmet medical needs and limited therapeutic options. At the forefront of this transformation is Trevi Therapeutics, whose investigational therapy Haduvio™ (oral nalbuphine extended-release) has demonstrated groundbreaking results in addressing chronic cough associated with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC). With a robust clinical pipeline, a favorable regulatory trajectory, and a $9 billion market opportunity in leading markets, Trevi's progress with Haduvio positions it as a compelling candidate for long-term value creation.

Clinical Progress: A Dual Mechanism with Proven Efficacy

Haduvio's mechanism of action-acting as a kappa-opioid receptor agonist and mu-opioid receptor antagonist-offers a novel approach to suppressing cough signals both centrally and peripherally. This dual modulation has translated into statistically significant outcomes in key trials. In the Phase 2b CORAL trial for IPF-related chronic cough, the highest dose of Haduvio (108 mg BID) achieved a 60.2% reduction in 24-hour cough frequency compared to a 16.9% reduction in the placebo group (p<0.0001) according to the topline results. Similarly, the Phase 2a RIVER trial for RCC reported a 67% reduction in cough frequency from baseline in patients receiving the therapy according to trial data. These results, presented at the ERS Congress 2025, underscore Haduvio's potential to address a critical unmet need: there are currently no FDA-approved treatments for chronic cough in IPF patients or those with RCC.

Trevi's next steps include an End-of-Phase 2 meeting with the FDA in late 2025 and the initiation of a Phase 3 program in early 2026 according to company announcements. The company's ability to navigate regulatory hurdles and translate these results into a robust Phase 3 design will be pivotal. However, the strong signal of efficacy observed thus far-particularly the dose-dependent response-provides a solid foundation for optimism.

Market Opportunity: A $9 Billion Landscape with Minimal Competition

The chronic cough therapeutics market is expanding rapidly, driven by rising prevalence of respiratory diseases and advancements in targeted therapies. In 2024, the market for chronic refractory cough in leading markets reached $9 billion, with the U.S. accounting for 50% of this total according to market analysis. By 2035, the market is projected to grow to $9.1 billion, reflecting a compound annual growth rate (CAGR) of approximately 0.1% according to industry outlook. This growth is fueled by the aging population, increased awareness of chronic cough as a distinct clinical entity, and the emergence of novel therapies like Haduvio.

Despite this growth, the current treatment landscape remains suboptimal. Patients are often prescribed off-label neuromodulators (e.g., opioids, gabapentin) or proton pump inhibitors, which carry risks of dependency and limited efficacy according to clinical reports. Emerging competitors, such as GSK's camlipixant (a P2X3 receptor antagonist) and Nocion Therapeutics' taplucainium, are also in development according to market intelligence. However, Haduvio's dual opioid receptor mechanism differentiates it by targeting both central and peripheral cough pathways, potentially offering broader efficacy.

Financial Strength and Strategic Positioning

Trevi's recent $115 million capital raise in 2025 has extended its cash runway into 2029 according to financial disclosures, providing ample resources to advance Haduvio through Phase 3 trials and pre-commercial activities. This financial fortification has attracted analyst attention, with some initiating "Buy" ratings based on the drug's clinical potential and the company's strategic clarity according to analyst reports. The capital infusion also allows Trevi to invest in patient-centric initiatives, such as digital health tools for cough monitoring, which align with market trends toward personalized care according to industry research.

Moreover, the absence of FDA-approved therapies for IPF-related and refractory chronic cough creates a first-mover advantage. If Haduvio secures regulatory approval, it could capture a significant share of the market, particularly given the lack of alternatives. Analysts estimate that the IPF-related chronic cough segment alone could generate $1.2 billion in annual revenue by 2030, assuming a 30% market penetration rate according to market analysis.

Risks and Considerations

While the outlook is promising, investors must remain cognizant of risks. Haduvio is still an investigational therapy, and its safety and efficacy have not yet been evaluated by regulatory authorities according to clinical data. Phase 3 trials will need to replicate the robust results observed in earlier studies while addressing potential side effects, such as sedation or gastrointestinal disturbances, which are common with opioid-based mechanisms. Additionally, the entry of competitors like camlipixant could fragment market share, necessitating aggressive commercialization strategies.

Conclusion: A Pathway to Long-Term Value

Trevi Therapeutics' progress with Haduvio represents a convergence of clinical innovation, market demand, and strategic financial planning. The drug's dual mechanism, supported by compelling Phase 2 data, positions it as a leading candidate in a therapeutic area starved of effective options. With a clear regulatory roadmap, a $9 billion market, and a capital base to sustain development, Trevi is well-positioned to transform chronic cough treatment and deliver substantial long-term value to stakeholders. As the company advances toward Phase 3 trials, the investment community will be watching closely for signals of its ability to navigate the final hurdles on the path to commercialization.