The partners have submitted a New Drug Application to the U.S. Food and Drug Administration for revefenacin as a treatment for adults with COPD. A New Drug Application is a formal request that the FDA consider approving a drug.
How Revefenacin works
Revefenacin is a long-acting muscarinic antagonist, or therapy that regulates the contraction and release of the lungs’ bronchial muscles. It is delivered as a mist.
Theravance and Mylan compared the pharmacological profile of revefenacin with those of two similar agents, tiotropium and glycopyrronium, in preclinical-trial studies. They showed that revefenacin’s effect lasts more than 24 hours, supporting once-a-day administration. The research also showed that it did a better job of zeroing in on the lungs than other agents.
Revefenacin in clinical trials
Revefenacin was tested in two Phase 2 clinical trials of COPD patients.
The first (NCT01704404) evaluated the safety of different doses of the therapy, and patients’ ability to tolerate it. It also evaluated the drug’s movement through the body and effect on the body.
The second trial (NCT02109172) assessed the safety and effectiveness of once- and twice-a-day doses delivered with a nebulizer, or mist-generating device. In both of the seven-day studies, revefenacin was compared with a placebo. The studies showed that patients tolerated revefenacin well when it was delivered as a mist, which limited its effect on organs besides the lungs.
A Phase 2b study (NCT02040792) compared four doses of mist-delivered revefenacin — 44, 88, 175, and 350 micrograms — with a placebo in people with moderate to severe COPD. Patients received it once a day for 28 days. Results from this study showed that the 88-, 175- and 350-microgram doses improved patients’ COPD, meeting the trial’s primary objective. In addition, patients tolerated the therapy well. Reported side effects included headaches, shortness of breath, and coughing.
The partners’ decision to submit a New Drug Application for revefenacin was based on the promising results of a Phase 3 trial program. It consisted of two three-month studies of the treatment’s effectiveness (NCT02512510 and NCT02459080) and a 12-month study of its safety (NCT02518139).
Researchers said the effectiveness studies, which covered more than 1,250 COPD patients, evaluated two doses of inhaled revefenacin inhalation. The trials, which ended in September 2016, showed that the treatment significantly improved patients’ lung function after 12 weeks of once-a-day dosing. The lung function measure researchers used was forced expiratory volume in one second, or the amount of air a person can exhale in a second after taking a deep breath.
The research team used spirometry to take another look at the lung function of 264 of the patients in the two effectiveness. They did the analysis 24 hours after the last dose on day 84. Revefenacin-treated patients displayed a significant improvement in lung function even 24 hours after receiving the last dose, compared with the placebo group.
Revefenacin also improved patients’ overall health, researchers said. One of the yardsticks they used was the St. George’s Respiratory Questionnaire, which measures respiratory patients’ health, well-being, and ability to perform daily activities. The other yardstick was the COPD Assessment Test, a questionnaire that measures COPD’s overall effect on a patient’s health.
The 12-month Phase 3 safety study in 1,055 COPD patients evaluated two doses of mist-delivered revefenacin — 88 and 175 micrograms. It compared the therapy’s safety, and patients’ ability to tolerate it, with that of a widely used treatment called tiotropium. The study showed that revefenacin led to fewer side effects than tiotropium.
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