The Neurokinin-1 Receptor Antagonist Orvepitant is a Novel Antitussive Therapy for Chronic Refractory Cough: Results from a Phase 2 Pilot Study (VOLCANO-1).

BACKGROUND: Substance P and the neurokinin-1 (NK-1) receptor are implicated in chronic refractory cough (CRC) pathophysiology. We assessed the efficacy and safety of orvepitant, a brain-penetrant NK-1 antagonist, in an open-label study in CRC patients.

METHODS: Thirteen patients with daytime cough frequency >3 to <250 coughs/hour took orvepitant 30 mg once daily for 4 weeks. Objective cough frequency was measured over 24 hours at Baseline and Weeks 1, 4, and 8. The primary endpoint was change from Baseline in daytime cough frequency at Week 4. Secondary endpoints included cough severity visual analogue scale (VAS) score, global ratings of change for cough frequency and severity, and Cough-specific Quality of Life Questionnaire score.

RESULTS: All patients completed the study. Mean Baseline cough frequency was 71.4/hour. A statistically and clinically significant improvement in objective daytime cough frequency was observed at Week 4: reduction from Baseline of 18.9 (26%) coughs/hour (95%CI: 9.6, 28.3; P<0.001). This effect was apparent at Week 1 (reduction from Baseline of 27.0 [38%] coughs/hour [95%CI: 11.4, 42.7; P=0.001]) and sustained after drug discontinuation at Week 8 (reduction from Baseline of 20.4 [29%] coughs/hour [95%CI: 3.2, 37.5; P=0.020]). Statistically significant improvements were seen for severity VAS and quality of life (QoL). Orvepitant was safe and well-tolerated.

CONCLUSIONS: Orvepitant resulted in a significant, and sustained improvement in objective cough frequency, severity VAS, and QoL; appeared safe; and merits further clinical investigation.