~ Statistically significant and clinically relevant improvements in patient reported outcomes in refractory chronic cough
~ Findings support further development of orvepitant in refractory chronic cough and meetings with the FDA and EMA are planned for Q4 2019 to discuss next steps
~ Results provide important insights into the evolving field of chronic cough and methods used to clinically evaluate symptoms
Stevenage, UK, 7 June 2019 – NeRRe Therapeutics today announces important results from the Phase 2b clinical trial (VOLCANO-2) with its neurokinin-1 receptor antagonist, orvepitant, in refractory chronic cough.
VOLCANO-2 was a 12-week, randomised, double-blind, placebo-controlled, Phase 2b dose-ranging clinical study designed to evaluate the efficacy, safety and tolerability of orvepitant in the treatment of refractory chronic cough in 315 patients from sites in the UK and North America. This was only the second Phase 2b dose ranging study in refractory chronic cough and the first with this mechanism.
Orvepitant, 30 mg once daily, resulted in statistically significant and clinically relevant improvements compared to placebo in the three key patient reported outcomes in the full analysis set at Week-12: Leicester Cough Questionnaire (p=0.009), Cough Severity VAS (p=0.034) and Urge-to-Cough VAS (p=0.005). The primary endpoint of awake cough frequency was not significant in this full analysis set, however in a pre-defined sub-group of higher frequency coughers, the reduction in cough frequency was near significant (p=0.066) at 12 weeks despite this sub-group analyses not being powered in the study. The trial confirmed the effectiveness of once daily dosing with orvepitant, and there were no safety concerns in this population; the excellent tolerability shown is seen as a major advantage of this class.
Professor Jaclyn Smith, Professor of Respiratory Medicine and Honorary Consultant, Director NIHR Manchester Clinical Research Facility added:
“Refractory chronic cough is a common and disabling condition and, with no proven therapies to treat the condition, there is a clear unmet medical need. The hypothesis being tested in this trial was that orvepitant could suppress the dysfunctional cough reflex and neuronal hypersensitivity which is thought to cause excessive coughing in patients with refractory chronic cough. The VOLCANO-2 study confirmed that orvepitant significantly improves the cough symptoms reported by patients and in so doing improves the quality of their lives. Orvepitant represents a novel first in class, non-opioid option to treat this common and debilitating condition.”
Commenting on the study outcome, Dr Mike Trower, Chief Scientific Officer and Founder at NeRRe Therapeutics said:
“Our intention was to design and execute a robust refractory chronic cough clinical study and, although there wasn’t a statistically significant reduction in awake cough frequency, the fact that patients are unequivocally reporting benefits cannot be underestimated.
“Awake cough frequency was monitored using an Ambulatory Cough Monitor and, whilst a very valuable tool, our data suggest that cough frequency is a more variable endpoint in patients with lower cough frequencies. In contrast, the cough frequency signal in this study was less variable in those patients with higher cough frequency at baseline, allowing a clear separation from placebo to be seen with the 30 mg once daily dose on all efficacy parameters, including cough frequency. This important observation will be incorporated in the design of the planned Phase 3 studies, thereby maximising their probability of success.”
The study outcomes support further development of orvepitant in refractory chronic cough and we intend to meet with the FDA and the EMA during Q4 this year to discuss next steps. The VOLCANO-2 data will be presented in full at a forthcoming international scientific meeting.
For more information, please contact:
Mary Kerr, CEO of NeRRe Therapeutics
Tel: +44 1438 906960
Consilium Strategic Communications
Mary-Jane Elliott/ Lindsey Neville/ Carina Jurs
Tel: +44 (0) 20 3709 5700
About NeRRe Therapeutics
NeRRe Therapeutics, a private UK based clinical-stage company founded in 2012 as a spin out from GSK, is developing a unique pipeline of three neurokinin (NK)-1 antagonists for the treatment of chronic cough caused by neuronal hypersensitivity associated with neurokinin-1 receptor system dysfunction.
The company is led by an experienced management team and is backed by leading international life sciences investors: Advent Life Sciences, Fountain Healthcare Partners, Forbion Capital Partners, and OrbiMed. NeRRe Therapeutics is based at Stevenage Bioscience Catalyst.
VOLCANO-2 was a randomised, double-blind, placebo-controlled, parallel group study that recruited subjects with refractory chronic cough of ≥1 year in duration and baseline awake cough frequency >10 coughs/hr. Subjects received placebo or one of three orvepitant doses (10, 20 or 30mg) once daily (OD) for 12-weeks. The primary endpoint was awake cough frequency at Week-12, recorded on a VitaloJAK ambulatory cough monitor. Other efficacy assessments included the Patient Recorded Outcomes (PROs): the Leicester Cough Questionnaire, Cough Severity Visual Analogue Scale (VAS) and Urge-to-Cough VAS. In total 315 subjects were randomised and 275 were evaluable at Week-12.
Orvepitant is a neurokinin-1 receptor antagonist that acts to reduce the central neural hypersensitivity that underlies chronic cough.