• HADUVI (oral nalbuphine ER), a product by Trevi Therapeutics, is a dual ĸ-opioid receptor agonist and µ-opioid receptor antagonist.
• HADUVI reduced 24-h cough frequency by 76.1% in IPF (idiopathic pulmonary fibrosis) patients, significantly outperforming the placebo’s 25.3% reduction.
• NAL ER demonstrated a 68–73% reduction in cough bouts across all intervals, significantly outperforming placebo and enhancing IPF patient quality of life.

Trevi Therapeutics’ presentation featuring their drug candidate, HADUVI (oral nalbuphine ER), was presented at the American Thoracic Society (ATS) 2024 International Conference being held in San Diego, held from May 17th to 22nd, 2024. The presentation showcased findings from a potentially crucial Phase II CANAL trial (NCT04030026) conducted in the UK. 

The impact of chronic cough is significant and often leads to a decline in patients’ social, physical, and psychological quality of life. In IPF, chronic cough may lead to worsening disease and may be associated with a higher risk of progression, death, or need for a lung transplant. Unmet needs in the current regime persist despite advancements in pharmacotherapy. Currently, there are no approved therapies for the treatment of chronic cough in IPF, and current treatment options provide minimal relief to patients.

A notable gap exists in addressing the specific cough symptoms experienced by IPF patients. The absence of therapies targeting the neurogenic and inflammatory aspects of IPF-related cough represents a significant unmet need. This shortfall in tailored therapeutic options hampers the effective alleviation of IPF-related cough, emphasizing the crucial necessity for the development of precise and focused treatments.

These limitations underscore the urgent need for novel therapeutic approaches, such as Trevi Therapeutics’ HADUVI (oral nalbuphine ER), which with its dual mechanism of action, acting as both an antagonist to the mu-opioid receptor and as an agonist to the kappa opioid receptor, Haduvio has the potential to significantly improve the quality of life of patients suffering from serious neurologically mediated conditions by targeting the central and peripheral nervous systems.

Trevi Therapeutics presented compelling findings at the ATS 2024 conference in San Diego regarding the post hoc analysis of nalbuphine extended-release (NAL ER) in reducing cough bouts in patients with IPF. In this Phase II trial, 24-h cough frequency data from the VitaloJAK monitor were analyzed at baseline and Day 21. A validated algorithm identified cough bouts within varying intervals, and negative binomial regression assessed treatment impact on cough frequency.

Patients with IPF treated with oral NAL ER exhibited a remarkable 76.1% reduction in 24-h cough frequency, compared to a 25.3% reduction in those receiving placebo. While the primary endpoint focused on the number of cough sounds per hour, the tendency of coughs to cluster into bouts holds significant clinical relevance for patients. This notable reduction highlights the superior efficacy of NAL ER in managing cough frequency, addressing a critical aspect of patient quality of life, and offering a promising therapeutic option for individuals with IPF.

In the post hoc analysis, cough data from 38 patients who completed at least one treatment period revealed significant findings. Treatment with NAL ER markedly reduced the rate of cough bouts by 68–73% compared to baseline, significantly outperforming placebo across all time intervals used to define a cough bout (all p < 0.0001). These substantial reductions with NAL ER were consistently large and statistically significant, irrespective of the cough bout definition (all p < 0.0001), whereas placebo reductions were minor and not statistically significant. These results were corroborated by a log-transformed mixed model for repeated measures analysis, further emphasizing the efficacy of NAL ER in reducing cough frequency.

In conclusion, consistent with the primary endpoint analysis, NAL ER significantly reduced the number of cough bouts in patients with IPF compared to placebo, regardless of the time interval used to define a cough bout and across various statistical analyses. Remarkably, NAL ER is the first drug to demonstrate a significant reduction in cough bouts in IPF patients, potentially surpassing its effect on standard cough frequency. This groundbreaking finding underscores NAL ER’s profound impact on alleviating cough, offering a novel and effective therapeutic option for improving patient quality of life in IPF.