TORONTO — An investigational long-acting drug for chronic obstructive pulmonary disease (COPD), delivered by nebulizer, improved patient quality of life in two pivotal studies, researchers said here.
In a pooled analysis of the placebo-controlled phase III trials 0126 and 0127, patients reported marked improvement on two scales, the St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) with revefenacin treatment, according to James Donohue, MD, of the University of North Carolina in Chapel Hill, and colleagues.
On both scales, patients reported “clinically meaningful” responses to the drug in secondary analyses, Donohue reported at CHEST, the American College of Chest Physicians annual meeting.
If approved, revefenacin would be the first once daily, long-acting muscarinic antagonist (LAMA) indicated for patients with COPD, Donohue said. He told MedPage Today it would be an important addition to the armamentarium of therapy for patients who require a nebulized treatment.
“What’s unique is that it’s in a nebulizer and it’s 24 hours,” he noted.
The results of the study are “important,” commented CHEST session co-moderator Arthur Gelb, MD, of the University of California Los Angeles. “Hopefully, [the drug] will reach clinical utilization soon.”
Donohue said the FDA is expected to make a decision soon, although it’s unclear which of two tested doses will get the nod.
Gelb told MedPage Today that one advantage of revefenacin is that it would be the “only LAMA that would be inline,” which would make it more economical to use for patients admitted to hospital.
The two studies were identical, with 1,229 patients randomly assigned on a 1:1:1 basis to placebo, 88 μg of revefenacin, or 175 μg of the drug. The primary endpoints were efficacy and safety over a 12-week period, he said.
Patients in the study were well balanced across the arms in terms of demographics. About half were current smokers and a similar proportion reported a modified Medical Research Council dyspnea score of at least 2.
Patients had moderate to severe COPD with a high risk of exacerbations, with most having GOLD system scores of 2 or 3 on numerical scoring or B and C on the alphabetical scale. Participants were “very typical” of patients in a COPD trial, Donohue said.
He noted that investigators have earlier reported that the drug had beneficial effects on breathing, with “robust” and statistically significant improvements, compared with placebo, in one-second forced expiratory volume (FEV1).
Also, the rate of adverse events in the three arms was similar, with “no really clear-cut effect in [adverse events] of the higher dose.”
Aside from efficacy and safety, key secondary analyses included patient reported outcomes, at baseline and on day 85 of treatment, on the SGRQ and CAT. The researchers recorded total scores and proportion of responders.
The analysis showed that in the 0126 study, total SGRQ scores were similar for both doses, with a significant drop of about 4 points from baseline, compared with a slight but non-significant increase among those on placebo. The greatest improvement was seen on the symptom subscale.
In the 0127 study, outcomes were much the same, but a greater than expected placebo response meant that the change with the lower dose of revefenacin did not reach statistical significance.
Over both studies, patients taking the drug were about 50% more likely to reach the 4-point improvement threshold than those on placebo, with an odds ratio of 1.56 for 88-μg dose and an OR 1.53 for the 175-μg dose.
In study 0126, both doses significantly improved total scores on the CAT, but again owing to the unexpected placebo response, only the 175-μg dose had significantly better scores in the 0127 study.
In 0126, both doses were significantly associated with a clinically meaningful CAT response, but in 0127, only the higher dose was significantly better than placebo.
Taken together, the studies demonstrated “improvements in the health status” of people using revefenacin, according to Donohue.
The study was supported by Theravance Biopharma. Several co-authors are company employees.
Donohue disclosed relevant relationships with Theravance Biopharma, Mylan, and Sunovion.
Gelb disclosed no relevant relationships with industry.