The experimental therapy SUN-101/eFlow is a combination of glycopyrrolate, named SUN-101, and eFlow, which is an innovative nebulizer closed system for the long-term, maintenance treatment of airflow obstruction in people with moderate-to-very severe COPD.
Sunovion Pharmaceuticals announced the FDA’s filing acceptance of its New Drug Application (NDA) for this treatment in October 2016. If approved, SUN-101/eFlow would be the first available nebulized long-acting muscarinic antagonist for adults with COPD. The expected action date by the FDA under the Prescription Drug User Fee Act (PDUFA) is May 29, 2017.
How does SUN-101/eFlow treatment for COPD work?
SUN-101’s key ingredient is glycopyrrolate, a long-acting muscarinic antagonist (LAMA) bronchodilator that connects to the muscarinic receptor subtypes M1 to M5. The M3 receptors are located on the muscle of the bronchi, and are responsible for bronchoconstriction.
The eFlow is an advance, handheld nebulizer that was developed by PARI Pharma and optimized for SUN-101 as a closed delivery system.
The SUN-101/eFlow development program, GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) included seven studies.
The Phase 1 GOLDEN-1 study (NCT01426009) aimed at determining steady-state efficacy and dose response profile (25, 50, 100, and 200 µg), and assess the safety and pharmacokinetic profile of SUN-101/eFlow compared with placebo and two drugs of reference (tiotropium and ipratropium, through a Handihaler DPI device). All once-daily doses of SUN-101 were well-tolerated, with a similar number of adverse events, and all demonstrated dose-related and significant improvements in FEV1 at the end of the study (day 7) compared to placebo, an article in the European Respiratory Journal reported.3
The GOLDEN-2 Phase 2 study (NCT1706536) compared different doses of SUN-101 with placebo in a study of its efficacy and safety in patients with moderate to severe COPD. Results showed that “SUN-101 demonstrated the rapid onset (≤5 minutes) of dose-related bronchodilation following single-dose administration (12.5–400 μg)” and “produced clinically meaningful improvements in lung function (FEV1) that were maintained over a 24-hour period at all doses >50 μg.” The treatment’s safety profile was also seen to be similar to tiotropium, according to a report published in the International Journal of Chronic Obstructive Pulmonary Disease in 2016.
GOLDEN-3 (NCT02347761) and GOLDEN-4 (NCT02347774) were Phase 3, 12-week-long studies that compared SUN-101/eFlow with placebo in adults with moderate-to-very severe COPD, given 25 or 50 mcg of SUN-101/eFlow or placebo twice a day. Their primary objective was the change in lung function at week 12, as measured by trough FEV1. Secondary objectives included standardized change from baseline in FEV area under the curve (AUC), change from baseline in trough forced vital capacity (FVC), 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, serious adverse events or major adverse cardiac events, and the number and percentage of study participants who discontinued the study due to treatment emergent adverse events. People already using an effective long-acting bronchodilator therapy, and those with very severe disease (post-bronchodilator FEV1 < 80% of predicted normal, or FEV1/FVC ratio < 0.70) and co-existing cardiovascular illness were included in both studies.
Both studies met their primary objective, with participants treated with SUN-101/eFlow showing a statistically significant change in trough FEV1 at the end of the study compared to placebo.
The GOLDEN-5 study (NCT02276222) was a long-term (48-week) and open-label safety study, with 1,087 moderate to very severe COPD patients receiving one of two treatments: SUN-101, 50mcg twice daily or tiotropium 18 mcg (Spiriva) once daily. The primary objectives were the number and percentage of patients with treatment-emergent adverse events, treatment-emergent serious events, and the number and percentage of participants who discontinued the study due to treatment-emergent events. Secondary objectives were the mean change from baseline over 48 weeks in trough FEV1, and the number and percentage of participants with major adverse cardiac events.
The tolerance of the treatment with SUN-101 twice daily and the number of major adverse cardiac events was similar to tiotropium 18 mcg.
GOLDEN-6 (NCT02038829) compared different SUN-101 doses (3, 6.25, 12.5, 50 mcg) to aclidinium in COPD patients 40 to 65 years of age, and GOLDEN-7 (NCT02512302) determined the amount of glycopyrrolate absorbed in the lungs of COPD patients, using the eFlow nebulizer compared to Seebri Breezhaler (glycopyrronium). Sunovion Pharma has not announced results for these two studies.
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