According to FDA’s warning letter, a 12-page brochure submitted to OPDP violated the FDCA because it contained false or misleading claims regarding the drug’s efficacy.
On August 15, 2023, the U.S. Food and Drug Administration (FDA) published a warning letter to AstraZeneca Pharmaceuticals LP, alleging that a professional sales brochure for its Breztri Aerosphere (budesonide, glycopyrrolate and formoterol fumarate) inhalation aerosol contained false or misleading claims regarding the drug’s efficacy.
In view of the warning letter—only the second of the year issued by the Office of Prescription Drug Promotion (OPDP)—companies should review their promotional materials to confirm that any efficacy claims are clearly supported by cited data and do not give rise to misleading impressions and regulatory scrutiny—even where such materials are intended for patients.
Background
Under Sections 352(a) and 331(a) of the Food, Drug and Cosmetics Act (FDCA), promotional communications including prescription drug advertisements and labeling are considered misbranded if they are “false or misleading” with respect to efficacy. Whether a promotional communication is “misleading” depends on, among other things, not only representations made or suggested in the promotional communication, but also the extent to which the promotional communication fails to reveal factual material in light of the representations made or with respect to consequences that may result from the use of the drug as recommended or suggested therein.
The Challenged Claims
Breztri Aerosphere was approved in July 2020 for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Breztri was not indicated for the relief of acute bronchospasm or for the treatment of asthma. While the drug does not have a boxed warning, it has 17 warnings and precautions for potential adverse reactions.
According to FDA’s warning letter, a 12-page brochure submitted to OPDP violated the FDCA because it contained false or misleading claims regarding the drug’s efficacy.
OPDP focused on two presentations suggesting that Breztri has been shown to have a positive impact on all-cause mortality in patients with COPD and to significantly reduce severe exacerbations—assertions that OPDP alleged were not supported by the trial data cited.
The first issue was the inclusion of a “prominent headline claim” stating “Difference Observed in Time to All-Cause Mortality (Over 52 Weeks)” above a graph from a clinical trial titled “Secondary Endpoint Study 1: Time to all-cause mortality in the ITT population,” which included claims that there is an observed relative difference in time to all-cause mortality between Breztri and its control cohorts.
Citing data published in the New England Journal of Medicine, the brochure claimed that there was a “49% observed relative difference in all-cause mortality with Breztri” versus other drugs. However, FDA observed that:
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 … . These suggestions are not supported by the cited references.
The second issue raised by OPDP was that the inclusion of a p-value in conjunction with a claim suggesting a statistically significant reduction in severe exacerbations when OPDP concluded that the results were not, in fact, statistically significant.
Although AstraZeneca included an explanatory footnote, as well as context regarding how the data was interpreted, FDA determined that they do not “mitigate the misleading impression” of the claims. Rather, FDA concluded “the presentation is concerning from a public health perspective because it overstates the efficacy of the drug and misleadingly represents that Breztri significantly reduces severe exacerbations.”
FDA has requested AstraZeneca to cease these violations and has given the company 15 working days to respond to the letter, outlining a plan to rectify these issues.
For More Information
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