Sunovion Pharmaceuticals Inc. (Sunovion)  has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for SUN-101/eFlow, an investigational treatment for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

The submission is based on the positive results of the GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) clinical trials program, which evaluated the efficacy and safety of SUN-101 (glycopyrrolate), a nebulized long-acting muscarinic antagonist (LAMA) delivered via an innovative investigational eFlow nebulizer system (SUN-101/eFlow). The GOLDEN program included three phase 3 clinical trials. GOLDEN-3 and GOLDEN-4 were phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter efficacy and safety trials comparing SUN-101/eFlow with placebo in patients with moderate-to-very severe COPD. GOLDEN-5 was a phase 3, 48-week, randomized, open-label, active-controlled, parallel-group, multicenter safety trial designed to evaluate the long term safety and tolerability of SUN-101/eFlow in patients with moderate-to-very severe COPD.

“Patients are at the heart of everything we do at Sunovion,” said Antony Loebel, M.D., executive vice president and chief medical officer at Sunovion, head of global clinical development for Sumitomo Dainippon Pharma Group. “This is an important milestone for us and the larger respiratory community, as we continue our mission of pioneering innovative treatments and therapies for COPD patients, their caregivers and healthcare providers.”

SUN-101 (glycopyrrolate) is a long-acting muscarinic antagonist (LAMA) bronchodilator delivered via the innovative, proprietary investigational eFlow nebulizer closed system for the treatment of patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The investigational combined product, consisting of SUN-101 and the closed eFlow nebulizer system which has been optimized for SUN-101 delivery, has not been approved by the US Food and Drug Administration (FDA) for the treatment of COPD.

GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer)-3 and GOLDEN-4 were phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety trials comparing SUN-101/eFlow with placebo in adults with moderate-to-very severe COPD. The GOLDEN-3 trial enrolled 653 people who were at least 40 years old, at 45 sites in the United States. The GOLDEN-4 trial enrolled 641 people who were at least 40 years old, at 49 sites in the United States. SUN-101/eFlow 25 mcg, SUN-101/eFlow 50 mcg or placebo was administered twice daily in these studies. The primary endpoint was the change from baseline in trough Forced Expiratory Volume in 1 second (FEV1) at week 12. Secondary endpoints included standardized change from baseline at week 12 in FEV1 area under the curve (AUC), change from baseline in trough forced vital capacity (FVC) at week 12, change from baseline in health status measured by St. George’s Respiratory Questionnaire and change in rescue medication use. Safety was assessed by the number of treatment-emergent adverse events (TEAE), serious adverse events (SAE) or major adverse cardiac events (MACE) and the number and percentage of study participants who discontinued the study due to TEAE.

GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer)-5 was a phase 3, 48-week, randomized, open-label, active-controlled, parallel-group, multicenter safety trial designed to evaluate the long term safety and tolerability of SUN-101/eFlow in adults with moderate-to-very severe COPD. The study enrolled 1,087 patients at 111 investigational sites in the United States and Europe. The study evaluated 50 mcg of SUN-101/eFlow delivered twice-daily and active comparator 18 mcg of Spiriva (tiotropium bromide) delivered once-daily by the HandiHaler device. The primary safety endpoints were: the number and percentage of study participants with treatment-emergent adverse events (TEAE), the number and percentage of study participants with treatment-emergent serious adverse events (SAE) and the number and percentage of study participants who discontinued the study due to TEAEs. The secondary endpoints are the mean change from baseline over 48 weeks in trough forced expiratory volume in one second (FEV1) for all subjects and number and percentage of subjects with MACE. The study included not only patients who were taking effective background long acting bronchodilator therapy but also patients with very severe disease and co-existing significant cardiovascular illness. Approximately 10 percent of the population were elderly (>75 years), 65 percent were classified as being high-risk cardiovascular patients and more than 40 percent were taking long acting bronchodilator therapy.

Chronic obstructive pulmonary disease, also known as COPD, includes chronic bronchitis and emphysema, and is a progressive respiratory disease that causes worsening obstruction to airflow in the lungs over time. Approximately 15.7 million adults in the US report that they have been diagnosed with COPD. It is estimated that several million more adults have undiagnosed COPD.3 COPD is responsible for over 120,000 deaths per year, making it the third leading cause of death in the U.S. COPD develops slowly and the symptoms often worsen over time, potentially limiting the ability to perform routine activities. Symptoms of COPD include constant coughing, wheezing, shortness of breath, excess production of mucus in the lungs, the inability to breathe deeply and the feeling of being unable to breathe.