FDA Accepts New Drug Application for Revefenacin in Treatment of COPD

The U.S. Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) submitted by Theravance Biopharma and Mylan for their collaborative compound revefenacin (TD-4208), a bronchodilator for the treatment of chronic obstructive pulmonary disease (COPD) in adults.

The two pharmaceutical companies are aiming to develop and commercialize revefenacin as the first once-daily long-acting muscarinic antagonist (LAMA) nebulizer for COPD and other respiratory illnesses.

Revefenacin belongs to the LAMA class of compounds that inhibit neurotransmitter receptors in the muscle cells and mucus glands of the lungs’ bronchia. LAMAs are used as maintenance bronchodilators in COPD, helping to keep narrowed airways open.

The FDA has authorized powder and liquid versions of LAMAs, but never a mist version that could be used as a nebulizer. If approved, revefenacin will be the first once-a-day mist LAMA bronchodilator to treat COPD.

The decision by the two companies to submit an NDA for revefenacin was based on the promising results of a Phase 3 trial program that included two 12-week clinical trials (NCT02512510 and  NCT02459080) evaluating the drug’s effectiveness, and a 12-month trial (NCT02518139) addressing its safety.

Revefenacin was shown to improve COPD patients’ lung function, as measured by the forced expiratory volume in one second (FEV1; the amount of air a person can exhale in a second after taking a deep breath) after 12 weeks of once-daily dosing.

The compound’s effect lasted 24 hours and both doses tested – 88 mcg and 175 mcg – were found to be safe and associated with fewer side effects than the FDA-approved COPD therapy Spiriva.

Most common adverse events reported in the trials – exacerbations, cough, dyspnea and headache – were comparable to those of standard-of-care treatments.

“The acceptance of our NDA moves us closer to providing COPD patients with access to once-daily, nebulized LAMA therapy. With positive results in our Phase 3 program, we believe that revefenacin is well positioned to fill this important need,” Rick E Winningham, chairman and CEO of Theravance Biopharma, said in a press release.

Theravance and Mylan believe that revefenacin is the best solution for COPD patients who require, or prefer, nebulized therapy.

The product’s stability as both a metered dose inhaler and a powder suggests that it could also serve as a combination therapy and a handheld product.

“Today, patients with moderate to severe COPD do not have access to a nebulized LAMA as a treatment option yet. We believe revefenacin, when approved, represents an important advancement in respiratory care by offering a convenient once-daily option for patients, and further strengthens Mylan’s robust and growing respiratory portfolio,” said Rajiv Malik, president and executive director of Mylan.