Post-marketing safety of ensifentrine in COPD

Ensifentrine is a newly approved inhaled dual phosphodiesterase 3 and 4 inhibitor for the maintenance treatment of chronic obstructive pulmonary disease. Because post-marketing safety experience is still limited, this study evaluated adverse event reporting patterns for ensifentrine. Quarterly US Food and Drug Administration (FDA) Adverse Event Reporting System/Adverse Event Monitoring System files from 2024Q3 to 2026Q1 were analyzed. Duplicate reports were removed using Case Identification Number (CASEID), FDA receipt date (FDA_DT), and Primary Identification Number (PRIMARYID), and the primary analysis was restricted to reports in which ensifentrine was recorded as the primary suspect drug. Preferred Terms (PTs) were mapped to Medical Dictionary for Regulatory Activities primary System Organ Class categories, and report-level disproportionality was assessed using reporting odds ratio, proportional reporting ratio, an information component approximation, and an observed-to-expected approximation. After deduplication, 2,831,030 records were reduced to 2,500,712 unique reports. Ensifentrine was identified in 1137 reports across all drug roles and in 823 primary-suspect reports, which included 1817 PT records. At the System Organ Class level, Respiratory, thoracic and mediastinal disorders was the only category meeting all predefined robust signal criteria. At the PT level, respiratory, cardiovascular, psychiatric/neuropsychiatric, and product quality- or medication-use-related terms were notable. Time-to-onset could be calculated for 139 reports, with a median of 12 days. Respiratory reporting patterns predominated in early post-marketing reports for ensifentrine. These findings should be interpreted as hypothesis-generating pharmacovigilance signals rather than estimates of incidence or causality.