Revefenacin: A Once-Daily, Long-Acting Bronchodilator For Nebulized Treatment Of COPD

Abstract

Bronchodilation with muscarinic antagonists, β₂-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using “duration and lung selectivity-by-design.” This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV₁) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.

Keywords:

• long-acting muscarinic antagonist
• LAMA
• bronchodilator
• inhaled
• once daily
• nebulizer

Acknowledgments

The medical writing support was funded by Theravance Biopharma US, Inc. (South San Francisco, CA, USA) and Mylan Inc. (Canonsburg, PA, USA). The authors acknowledge Esther Berkowitz, MBChB, and Ritu Pathak, PhD, for medical writing and Frederique H. Evans, MBS, for editorial assistance in the preparation of the manuscript (Ashfield Healthcare Communications, Middletown, CT, USA).

Abbreviations

AE, adverse event; BPC, 4-piperidyl biphenyl-2-ylcarbamate; DPI, dry powder inhaler; GOLDEN, Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer; ICS, inhaled corticosteroid; hERG, human ether-à-go-go; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; LS, least squares; MACE, major adverse cardiovascular event; MDI, metered-dose inhaler; OTE, overall treatment effect; PIFR, peak inspiratory flow rate; REV, revefenacin; SAE, serious adverse event; SGRQ, St George’s Respiratory Questionnaire; SMI, soft-mist inhaler; TIO, tiotropium.

Data Sharing Statement

Theravance Biopharma (and its affiliates) will not be sharing individual deidentified participant data or other relevant study documents.

Disclosure

JFD is a consultant and advisory committee member for Theravance Biopharma US, Inc., AstraZeneca, GSK, Novartis Pharmaceuticals, Mylan Inc., and Sunovion Pharmaceuticals.

DAM has served on advisory boards for AstraZeneca, Boehringer Ingelheim, GSK, Grifols, Sunovion Pharmaceuticals, Theravance Biopharma US, Inc., and Trevi, and is on the speaker’s bureau for AstraZeneca, Boehringer Ingelheim, and Sunovion Pharmaceuticals.

SS is a consultant and advisory committee member for Theravance Biopharma US, Inc., and received research support from Mylan Inc.

The authors report no other conflicts of interest in this work.