FDA Approves Twice-Daily Inhaler for COPD

The US Food and Drug Administration approved a twice-daily aclidinum and formoterol fumarate (Duaklir Pressair) treatment for the maintenance of chronic obstructive pulmonary disease (COPD).

Aclidinium/formoterol fumarate is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA) aclidinium and the long-acting beta agonist (LABA) formoterol, which is delivered twice daily via a pre-loaded, breath-actuated, multi-dose inhaler. According to its manufacturer, Circassia Pharmaceuticals Inc., it is the only twice-daily LAMA/LABA in the US with COPD exacerbation data included in its prescribing information.

Circassia and AstraZeneca establsihed a commercial collaboration in 2017 where Cicassia has exclusize US commercialization rights to the treatment and AstraZeneca is responsible for the product’s development and regulatory submission.

“Our collaboration with AstraZeneca throughout the Duaklir Pressair regulatory process has been overwhelmingly positive,” said David Acheson, senior vice president, US Commercial, Circassia. “We look forward to bringing Duaklir Pressair to market in the coming months as an important expansion of Circassia’s COPD and respiratory health portfolio.”

The FDA approval is based upon the results of multiple studies including ACLIFORM, AUGMENT, and the AMPLIFY clinical trial. phase III clinical trial compared the efficacy and safety of inhaled the daily aclidinum/formoterol fumarate treatment to its individual components aclidinium and formoterol, and to inhaled tiotropium (Spiriva Handihaler) in 1,583 patients with moderate-to-very-severe symptomatic COPD.

The trial found that the treatment significant improved lung function versus aclidinium, significantly increased lung function versus formoterol, and improved overall nighttime and early-morning symptom severity scores compared to aclidinium or formoterol at 24 weeks. Additionally, patients saw significant improvements in over early-morning symptom severity score versus tiotropium and a pre-planned substudy found significantly improved lung function compared to tiotropium.

The proportion of patients reporting treatment-related adverse events in the study were similar between groups. The most common adverse events reported were COPD exacerbations (18.3%), nasopharyngitis (11.8%), and headache (4.9%). The incidence of series adverse events (7.85%), major adverse cardiovascular events (0.7%), and adverse events leading to discontinuation (7.1%), or death (0.5%) were similar across treatment groups.

“The results of the AMPLIFY trial showed us that the benefits of the combination were more than its individual components in terms of efficacy, with a comparable safety profile,” said Sanjay Sethi, MD, professor and chief of Pulmonary, Critical Care and Sleep Medicine at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, and investigator on the AMPLIFY trial. “The study also showed a reduction in the use of rescue inhalers in the Duaklir Pressair group, which is a good measure of symptom control in symptomatic COPD patients. Duaklir Pressair will be a welcome addition to the armamentarium to help these patients.”

Aclidinum/formoterol fumarate is the second Circassia treatment to receive an FDA approval in recent weeks. In late March, aclidinium bromide inhalation powder (Tudorza Pressair) received FDA approval for a Supplemental New Drug Application (sNDA) to include data for the reduction of COPD exacerbations and hospitalizations. Approval of the sNDA for aclidinium bromide inhalation powder was based upon data from the ASCENT trial.