FDA WARNING_LETTER - AstraZeneca Pharmaceuticals LP - August 15, 2023

The FDA's Office of Prescription Drug Promotion (OPDP) issued a Warning Letter to AstraZeneca regarding a professional sales aid (US-68433) for BREZTRI AEROSPHERE™ (budesonide, glycopyrrolate, and formoterol fumarate) inhalation aerosol. The sales aid is deemed false or misleading concerning Breztri's efficacy, misbranding the drug under 21 U.S.C. 352(a) and 331(a), and 21 CFR 202.1(e)(5).

The primary violations include misleading claims about Breztri's impact on all-cause mortality (ACM) in COPD patients, suggesting a reduction in the risk of death. These claims, such as "DIFFERENCE OBSERVED IN TIME TO ALL-CAUSE MORTALITY (OVER 52 WEEKS)," are not supported by the ETHOS trial data due to statistical testing hierarchy failures and potential confounding factors like abrupt withdrawal of inhaled corticosteroids (ICS). The FDA states no drug has been shown to improve ACM in COPD.

Additionally, the sales aid misleadingly presents a "20% REDUCTION VS ICS/LABA" in severe exacerbations with an associated p-value of 0.02, implying statistical significance. However, this reduction was not statistically significant per the ETHOS trial's predefined testing strategy, where the p-value (0