Extended-Release Nalbuphine Improves Patient-Reported Refractory Chronic Cough Within 1 Week

Oral extended-release nalbuphine significantly improved perception of cough severity and frequency among treated patients with refractory chronic cough (RCC) compared to placebo at 7, 14, and 21 days, according to new late-breaking data presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago, IL, this week.

The new phase 2A trial data, presented by Imran Satia, MD, PhD, associate professor at McMaster University, showed significantly improved measures of patient-reported outcomes including 24-hour objective cough frequency, Patient Global Impression of Severity for Cough (PGI-C) and Leicester Cough Questionnaire (LCQ) when patients received a twice-daily regimen of nalbuphine, titrated once-weekly over 3 weeks (27 mg, 54 mg, 108 mg).

The promising findings from the randomized trial of 66 patients with RCC (mean age, 60.2 years; mean cough frequency, 34.7 coughs per hour) carry particular weight for this patient population. There are currently no US Food and Drug Administration (FDA)-approved therapies to treat RCC, and cases with no resolve to the underlying disease are generally treated with neuromodulators.

In an interview with HCPLive during CHEST 2025, Satia discussed the scope and severity of RCC as an undertreated condition in pulmonary medicine. Despite being one of the most common reasons for referral to a specialist, clinicians often need to rely on a treatable, underlying diagnosis to achieve positive patient outcomes — such as asthma or other airway diseases.

“[RCC patients] are often coughing sometimes 500-600 times per day,” Satia said. “And they're often coughing for 5 or 10 years. They're getting incontinence of urine, syncope, pre-syncope, chest pains, difficulty talking, difficulty doing their jobs. It has a significant impact on their quality of life — both physical, social, psychological — and often, they go into multiple specialties, seeing multiple doctors, and there's no treatments.”

Extended-release nalbuphine has dual-acting properties — predominately functioning on the central nervous system, but also the peripheral nervous system. Its benefit to RCC is based on the hypothesis that suppressing hypersensitivity particular in the vagus nerve would result in reduced, and less severe, coughing.

The value of these latest phase 2A data are that they show this specific intervention strategy is associated with early changes to patient-reported outcomes. What stands out to Satia is the quick response to treatment — patients observing significant benefit within 7 days of initiating treatment. Patients receiving extended-release nalbuphine reduced their mean coughs from 30-40, to 15-20 per hour.

“Regulators want to know that just because coughing less, they are actually feeling better as well,” Satia said. “They've got to feel subjectively and objectively better.”

References

1. Satia I, Birring S, Garin M, Cassella J. Patient-Reported Outcomes from a Phase 2A Trial of Extended-Release Nalbuphine for Patients with Refractory Chronic Cough. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.
2. Visca D, Beghè B, Fabbri LM, Papi A, Spanevello A. Management of chronic refractory cough in adults. Eur J Intern Med. 2020;81:15-21. doi:10.1016/j.ejim.2020.09.008