Trevi Therapeutics reports promising results for Oral Nalbuphine in human abuse potential study

Trevi Therapeutics, Inc., a clinical-stage biopharmaceutical company, announced positive oral nalbuphine results from its human abuse potential (HAP) study evaluating the investigational therapy Haduvio™ for chronic cough treatment associated with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC). The findings, showcasing low abuse potential, highlight the therapy’s safety profile and potential impact on treating challenging cough conditions.

The HAP study, conducted as a double-blind, double-dummy, placebo-controlled, five-way crossover trial, assessed “Drug Liking” scores to evaluate low abuse potential. Results indicated statistically significant results for nalbuphine clinical doses, demonstrating reduced scores compared to IV butorphanol, an opioid analgesic commonly used in such trials.

Key Findings

The human abuse potential study’s primary endpoint measured “Drug Liking” using a 100-point visual analog scale. Clinical doses of oral nalbuphine (81mg and 162mg) achieved statistically significant results compared to IV butorphanol (p<0.0001 for both doses).

A supratherapeutic dose (486mg) also exhibited low abuse potential, with numerically lower “Drug Liking” scores than IV butorphanol, though statistical significance was not achieved.

Secondary endpoints further validated the safety and efficacy of nalbuphine clinical doses, assessing pharmacodynamic markers like patient-reported outcomes. Notably, the trial revealed no serious adverse events, reinforcing the drug’s safety profile in chronic cough treatment.

Dr. James Cassella, Chief Development Officer at Trevi Therapeutics, highlighted that the oral nalbuphine results support the study’s robustness and reflect the well-established safety of the drug. Dr. Jack Henningfield of Pinney Associates emphasised that nalbuphine’s long-standing status as an unscheduled drug in the U.S. indicates minimal risk of abuse or overdose.

Addressing Critical Needs in Chronic Cough Treatment

Trevi Therapeutics is developing Haduvio, an investigational therapy targeting idiopathic pulmonary fibrosis-related cough and RCC, conditions that affect millions of U.S. patients. Chronic cough often results in severe physical, social, and psychological impacts, with limited chronic cough treatment options currently available.

Haduvio acts on the cough reflex arc through kappa agonist and mu antagonist pathways, addressing cough hypersensitivity both centrally and peripherally. By demonstrating low abuse potential in the HAP study, Trevi strengthens its regulatory case for providing patients with a much-needed alternative to current therapies.

Next Steps for Oral Nalbuphine

Trevi plans to integrate these oral nalbuphine results into future discussions with the U.S. Food and Drug Administration (FDA). The human abuse potential study findings, along with data from ongoing clinical trials, will inform its submission for chronic cough treatment approval.

The company remains committed to addressing the unmet needs of patients with IPF-related chronic cough and RCC, leveraging Haduvio’s low abuse potential profile to provide safer, effective options for this patient population.