FDA CRL - AstraZeneca AB

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to AstraZeneca AB on September 30, 2019, regarding its New Drug Application (NDA 212122) for Breztri Aerosphere (budesonide, glycopyrrolate, and formoterol fumarate) 160/9/4.8 mcg Inhalation Aerosol. Submitted on November 30, 2018, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, the application was denied due to insufficient evidence supporting the efficacy and safety of the drug for chronic obstructive pulmonary disease (COPD).

The primary issue was the clinical data, as the single Phase 3 pivotal trial failed to meet its co-primary endpoint, which aimed to establish the contribution of budesonide to the combination product. Consequently, all secondary endpoints also lacked statistical significance, providing no additional support for efficacy. The FDA requires AstraZeneca to conduct further clinical trials to demonstrate the product's overall efficacy and the specific role of budesonide.

Additional required actions include updating the prescribing information in a specific format, resubmitting the proposed proprietary name (Breztri Aerosphere) for re-evaluation with the updated application, and providing a comprehensive safety update. This safety update must detail new data from all studies, re-tabulate adverse events, provide narrative summaries for serious events and trial discontinuations, update exposure information, and summarize worldwide safety experience. AstraZeneca must address all identified deficiencies and resubmit the application within one year.