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Evaluating Revefenacin as a Treatment for COPD

Wallace Stephens
In a review of revefenacin, researchers found that the drug may have the potential to serve as long-acting bronchodilator for once-daily treatment of respiratory disorders such as chronic obstructive pulmonary disease (COPD). 
Revefenacin was found to have the potential to serve as long-acting bronchodilator for once-daily treatment of respiratory disorders such as chronic obstructive pulmonary disease (COPD), according to a review of the drug’s effects in Cureus.

The goal of pharmacological therapy in COPD is to reduce the frequency and severity of exacerbations, relieve debilitating symptoms, and improve the overall health of individuals with the disease. Nebulized therapy options for treatment of COPD are currently limited and use of hand-held devices can result in poor adherence, inaccurate dosing, and poor clinical outcomes. However, revefenacin, sold as Yupelri by Theravance Biopharma, offers an opportunity for patients that prefer or require nebulized therapy to be treated with a potent, once-daily long-acting muscarinic antagonist (LAMA). Revefenacin is the first and only once-daily nebulized bronchodilator approved by the FDA to treat COPD.

As data regarding revefenacin’s role was limited, researchers reviewed existing publications to examine outcomes from studies that tested the drug as a treatment for COPD. The review highlighted both the target and off-target effects of revefenacin and examined the benefits and drawbacks of the drug. Researchers also compared revefenacin to other anti-muscarinic agents.  

“This comprehensive review of ours will benefit the medical professionals in knowing about better treatment options for COPD patients,” the authors wrote.

Revefenacin is an investigational LAMA in late-stage development as a nebulized inhalation solution. It was developed to produce long-acting bronchodilation and a high degree of lung selectivity with a once-daily dose. Revefenacin is delivered via a standard jet nebulizer connected to an air compressor. The approved dosage was 175 micrograms administered once per day.

Revefenacin binds competitively and reversibly to muscarinic receptor type 3 (M3) in the airway smooth muscle and causes bronchodilation. A study found that the drug had a high degree of lung selectivity. It was more selective for M3 than type 2 or type 1 receptors. Its dissociation half-life for M3 was 82 minutes and 6.9 minutes for type 1. Revefenacin was also found to be site-specific.

Results of a study found the bronchoprotective effects of the drug could be observed as early as 5-minutes after administration of a dose. The effects were sustained for an extended period of time and lasted up to 24 hours. The estimated 24-hour potency was 45.0 mg/mL.

Another study found that a once-daily dose of revefenacin provided long-term improvement in trough forced expiratory volume in 1 second (FEV1) on day 28 over placebo. In another study that involved 24-hour serial spirometry, it was found that compared with placebo, 88 or 175 micrograms of revefenacin was associated with significant improvements in trough FEV1 at all-time points on day 84.

A study also found that revefenacin was well-tolerated by patients and did not produce typical systemic adverse effects associated with anti-cholingeric therapies. Another study found that revefenacin produced fewer side-effects, including a decrease in occurrence of dry mouth from 4% to 1.4%, compared to tiotropium.

Findings from another study showed patients who used revefenacin also used fewer rescue medications. Doses greater than or equal to 88 micrograms reduced the average number of daily albuterol puffs by 1 or more.

"Revefenacin has the potential to be a long-acting bronchodilator for once-daily treatment of respiratory diseases," the authors concluded. "Its greater functional selectivity for the lung may translate to an improved tolerability profile compared with the other muscarinic receptor antagonists."

Reference

Maqsood MH, Rubab K, Maqsood MA. The role of revefenacin in chronic obstructive pulmonary disease. Cureus. 2019;11(4). doi: 10.7759/cureus.4428.

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