AstraZeneca hit with FDA warning letter over 'misleading' Breztri efficacy claims

AstraZeneca’s promotion of Breztri Aerosphere has landed it in hot water with the FDA. The agency says an AstraZeneca sales aid made “misleading” claims about the effect of the inhaler on all-cause mortality, prompting it to send a warning letter to CEO Pascal Soriot.

Following FDA regulations, AstraZeneca sent the sales aid and other Breztri promotional materials to the FDA for review. The agency found fault with the sales aid. According to the FDA, the document includes the “prominent headline claim” about a difference in time to all-cause mortality between the Breztri and control cohorts in a chronic obstructive pulmonary disease (COPD) clinical trial. 

Citing data published in 2020 and 2021, the sales aid claimed a “49% Observed relative difference with BREZTRI vs LAMA/LABA.” The FDA took a dim view of the suggestion that Breztri had a positive impact on all-cause mortality.

“These claims and presentation, in the context of a promotional communication describing the safety and efficacy of Breztri, are misleading because they suggest that Breztri treatment has been shown to have a positive impact on all-cause mortality and reduce the risk of death in COPD patients,” the FDA wrote in its warning letter. “These suggestions are not supported by the cited references.”

A secondary endpoint of one of the cited studies showed “the risk of death (on and off treatment) with BGF 320”—triple therapy with the Breztri active ingredients budesonide, glycopyrrolate and formoterol fumarate—“was 49% lower than that with [glycopyrrolate and formoterol fumarate].” 

However, as the FDA notes in its warning letter, “endpoints higher in the analysis hierarchy” failed, and, as such, “the trial does not allow for any conclusions to be drawn from the [all-cause mortality] data.” The FDA also called out a perceived issue with the trial design, noting that the “abrupt withdrawal of [inhaled corticosteroids] may have been a confounding factor when analyzing any positive effect on [mortality].” 

In the FDA’s view, the “claims and presentation are concerning from a public health perspective because they overstate the efficacy of the drug and misleadingly suggest that Breztri will have a positive impact on [all-cause mortality] and reduce the risk of death in COPD patients.” The warning letter also criticizes the use of a p-value that gives a misleading impression that another outcome was statistically significant. 

The FDA sent the warning letter Aug. 4 but only published it online Aug. 15. AstraZeneca had 15 working days from the date it received the letter to respond in writing with a “plan for discontinuing use of such communications, or for ceasing distribution of Breztri.”