Despite recent reductions-in-force (“RIFs”) at the Food and Drug Administration (“FDA” or “Agency”), the Agency’s Office of Prescription Drug Promotion (“OPDP”) has signaled that enforcement remains a priority. On April 28, 2025, OPDP issued its third Untitled Letter of the year — notably, the first following the April 1 RIFs, which impacted OPDP staffing. As of now, OPDP appears to be on pace to exceed the number of Untitled Letters issued in 2024. Last year, OPDP issued five Untitled Letters in total, with four of those released during the latter half of the year (July through October).
OPDP issued this Untitled Letter in connection with a company’s submission of a promotional speaker deck and accompanying speaker notes for an oral contraceptive drug, submitted pursuant to Form FDA 2253. According to FDA, the speaker deck made “false or misleading claims about the risks” of the drug, which were particularly concerning given that the drug product is “associated with a number of serious and potentially life-threatening risks, including a boxed warning regarding increased risk of serious cardiovascular events from cigarette smoking and [combined hormonal contraceptives use (“CHC”)].”
The drug product was approved by FDA in 2021, and OPDP provided the company with advisory comments in January 2022 on draft promotional communications. Thus, FDA expressed concern that the company was “promoting [the drug] without presenting the serious risks of the drug in a truthful and non-misleading manner, despite OPDP’s prior comments.”
False and Misleading Claims and Presentations about Risk
A central issue cited in the Untitled Letter involved misleading claims with respect to the presentation of risk. Specifically, the speaker deck included claims that suggested that the drug product, because of its active estrogen ingredient, estetrol, was safer than other forms of CHC, including those that contained ethinyl estradiol, a claim that has not been substantiated.
Specifically, the speaker deck included, among other things, “numerous claims and presentations comparing the pharmacologic properties and purported benefits of estetrol (e.g., “claims of ‘low-impact,’ and ‘minimal effect on the liver'”) to those of other estrogens.” According to OPDP, these claims “misleadingly” suggested that the drug product was “unique” and “intrinsically different” from other estrogens, thus making it a “safer form of estrogen-containing oral contraception due to its ‘low-impact'” properties.
OPDP also took issue with claims, with associated p-values, suggesting that the drug demonstrated a statistically significant difference in several observed endocrine and hemostatic parameters as compared with the two reference CHCs. However, that suggestion was not supported by the studies submitted to the Agency. The safety study did not prespecify the thresholds for clinically relevant differences in effects of the study products on the various endocrine and hemostatic parameters. As a result, the data was considered “descriptive” and not supportive of the conclusions presented. While the company included a disclaimer that “[n]o clinical differences should be made from the results shown…directly preceding these claims and presentations…,” the statement did not “mitigate the misleading impression.”
The slide deck further minimized serious known risks associated with the use of the drug product, including the potential for thromboembolic events, liver-related issues, glucose intolerance and hypertriglyceridemia. These risks were well-documented in the product’s Prescribing Information (“PI”). For example, the speaker deck included claims regarding the drug’s minimal impact on liver parameters and clotting factors; however, the drug is contraindicated in individuals with hepatic disease and is associated with increased risks of vascular complications.
Moreover, the slide deck included claims that suggested that the drug may be suitable for individuals with or at risk for breast cancer. Specifically, OPDP took issue with claims that estetrol has a “low impact on breast tissue…and does not stimulate breast tissue.” These claims were not substantiated by human clinical data and could mislead health care providers (“HCPs”) into thinking that the drug is a safer option for patients who had or have had breast cancer, when in fact, the drug is contraindicated in individuals with a current diagnosis or history of breast cancer which may be sensitive to certain hormones.
Finally, the slide deck also omitted material facts regarding the risks of hyperkalemia, migraines with aura and menstrual bleeding irregularities associated with the drug product. While the speaker deck included a statement directing HCPs to consult the full PI and included a hyperlink to the PI throughout the speaker deck, OPDP again emphasized that these statements did not mitigate the “misleading minimization of risks” associated with the use of the product.
Practical Takeaways
- Even if years have passed, failing to reflect OPDP’s prior feedback may suggest that the company disregarded earlier regulatory concerns.
- Minimizing or omitting serious risks (e.g., boxed warnings, contraindications), especially for drugs with a boxed warning, undermines truthful and non-misleading promotion and will lead to an enforcement action from OPDP.
- Disclaimers and hyperlinks to the PI, while they can be helpful, do not mitigate the impact of misleading claims or omitted risks.
- Ensure all promotional content is thoroughly vetted by Medical, Legal and Regulatory (“MLR”) reviewers, with clear documentation of supporting data and intended claims. MLR teams remain key in ensuring that promotional materials are balanced and that there is substantiation for all claims used in promotion.
- To date, OPDP is on pace to surpass the number of letters issued in 2024. With the potential for increased attention on direct-to-consumer advertising, it will be important to watch whether this becomes a primary focus for OPDP in the remainder of 2025.
For more information on the advertising and promotion of drugs, biologics or medical devices, please contact:
- Carolina Wirth at (202) 780-2989 or cwirth@hallrender.com;
- Jemalyn Harvey at (202) 780-2990 or jharvey@hallrender.com; or
- Your primary Hall Render contact.
Hall Render blog posts and articles are intended for informational purposes only. For ethical reasons, Hall Render attorneys cannot—outside of an attorney-client relationship—answer specific questions that would be legal advice.
