Orvepitant: A Novel Antitussive Therapy for Chronic Refractory Cough?

Male doctor examining coughing senior patient in clinic
Orvepitant treatment in intractable chronic refractory cough has demonstrated clinically relevant and sustained improvements in cough frequency and quality of life.

Use of orvepitant in patients with intractable chronic refractory cough (CRC) has demonstrated clinically relevant and sustained improvements in objective cough frequency and subjective measures including quality of life (QoL), according to a pilot efficacy evaluation published in CHEST.

The associated symptoms of chronic coughing, such as retching, vomiting, and urinary incontinence, significantly affect QoL in that many individuals avoid public places and social gatherings to prevent embarrassment. Because there are no licensed treatments for CRC, there is an urgent need to identify effective and well-tolerated therapies.

Neurokinin-1 receptor antagonists have previously demonstrated promise as treatments for cough; therefore, researchers assessed the efficacy and safety of orvepitant 30 mg once daily for 4 weeks in an open-label study in 13 patients with a daytime cough frequency of >3 to <250 coughs/h. They found a statistically and clinically significant improvement in objective daytime cough frequency at week 4, with a reduction from baseline of 18.9 coughs/h (26%; P <.001). This effect was initially seen at week 1 and was sustained after drug discontinuation at week 8. In addition, statistically significant improvements were seen for cough severity and QoL, and orvepitant was safe and well tolerated.

“Orvepitant is a promising therapy for CRC that may modulate cough reflex hypersensitivity through a central-acting mechanism of action,” the authors concluded. A larger study is now underway to confirm these initial findings (ClinicalTrials.gov Identifier: NCT02993822).

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Disclosure: This clinical trial was supported by NeRRe Therapeutics, Ltd. Please see the original reference for a full list of authors’ disclosures.


Smith J, Allman D, Badri H, et al. The neurokinin-1 receptor antagonist orvepitant is a novel antitussive therapy for chronic refractory cough: results from a phase 2 pilot study (VOLCANO-1) [published online August 14, 2019]. CHEST. doi:10.1016/j.chest.2019.08.001