AT CHEST 2017
TORONTO (FRONTLINE MEDICAL NEWS) – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status irrespective of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.
There are currently no nebulized LAMAs approved for use in the U.S.
Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.
“Glycopyrrolate works,” reported Dr. Ohar. “It improves FEV1 [at week 12], not only in the statistically significant manner but in a clinically significant manner, both at the 25-microgram and 50-microgram dose…And when you cut the data according to FEV1, you again see a statistically significant improvement regardless [of whether] your FEV1 at baseline was less than 50% of predicted versus greater than or equal to 50%.”
Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.
Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.
The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.
Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.
“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.
GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.
Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.
Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.
