An example of OPDP’s focus on the presentation of risk information was its August 2020 warning letter to Sprout Pharmaceuticals for a radio advertisement for Addyi (flibanserin) tablets, which are indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder. OPDP criticized the ad for omitting information in the label’s boxed warning that use of the drug and alcohol together close in time increases the risk of severe hypotension and syncope. The ad entirely failed to mention the dangers of concurrent alcohol use, despite Sprout's history of prior correspondence with the agency regarding inclusion of the warning about alcohol use in their promotional communications.
The warning letter to Sprout further cited the ad for neglecting to mention all the contraindications associated with the use of Addyi, the warning and precaution regarding CNS depression, and the boxed warning that use of Addyi with certain prescription medications or in patients with liver problems increases the risk of severe hypotension and syncope. Further, OPDP asserted that the ad created a misleading impression regarding the scope of the approved use of Addyi.[1]
While the Sprout letter criticized a radio advertisement, the majority of OPDP’s 2020 letters addressed drug manufacturers’ use of electronic communication platforms. For example, OPDP sent a warning letter in February to Outlook Pharmaceuticals over the company’s sponsored link for Procentra (dextroamphetamine sulfate) oral solution, which FDA said presented information about the benefits of the drug while failing to include any risk information. OPDP found this especially concerning because Procentra, a stimulant used for the treatment of Attention-Deficit Hyperactivity Disorder, is a schedule II controlled substance associated with serious and potentially life-threatening risks, including those contained in the drug’s Boxed Warning that describes the “high potential for abuse” of the drug and states that “misuse may cause sudden death and serious cardiovascular adverse events.”
We have previously summarized OPDP’s September letters to Nalpropion and Nephron (online here), which similarly rebuked drug sponsors for failing to communicate risk information in online formats. The warning letter to Nalpropion cited a sponsored link for Contrave, a drug indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management. The letter pointed out that Orexigen, a prior sponsor of Contrave, also received an untitled letter in 2017 for a television advertisement, which OPDP said created a misleading impression about the safety of Contrave. Although the sponsored link included the statement “View Important Safety Info & Boxed Warning,” OPDP concluded that this statement fails to mitigate the misleading omission of risk information. The sponsored link was said to create a misleading impression regarding the efficacy of Contrave by “selectively presenting more favorable data,” among other issues.
Meanwhile, the September warning letter to Nephron cited emails sent by CEO Lou Kennedy and a sales representative claiming that their generic inhaled asthma medication budesonide product can treat COVID-19 symptoms. The sales representative’s email also included a link to a YouTube video purporting to show a physician successfully treating a COVID-19 patient with budesonide and an antibiotic. This is notable as one of the few OPDP warning letters in recent years that cites promotion of an unapproved use, which is likely due to the focus FDA has been giving to unproven COVID-19 therapies since March.
The final OPDP letter of the year came in November, when the agency, in an untitled letter, cited Azurity Pharmaceuticals for a health care professional email that allegedly created a misleading impression about the safety and effectiveness of Xatmep, which is indicated for treating pediatric patients with acute lymphoblastic leukemia (ALL) and for the management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA). Reflecting the agency’s continued focus on the manner in which risk information is displayed, the letter characterized Azurity’s email as “prominently” presenting drug benefit claims in the body of the email in a bulleted list, while presenting the risk information “after the signature block.”
OPDP noted that the drug treats a vulnerable patient population, and bears a Boxed Warning over possible “serious and life-threatening risks.” OPDP also observed that although the email included the Boxed Warning, it omitted other important warnings and precautions, including that “mistaken daily use of the recommended dose has led to fatal toxicity.” Finally, OPDP asserted that the email suggested that Xatmep is approved for use in patients of all ages, without specifying that the indication is only for pediatric patients, and only as part of a combination therapy.
The enforcement letters sent by OPDP in 2020 provide useful guidance on the agency’s focus, which appears to be shifting toward promotion in online media — the use of which is likely to continue to accelerate in drug promotion as the COVID-19 pandemic lingers, and beyond. We will continue to monitor these OPDP enforcement actions, particularly as new leadership at the FDA and OPDP is established in the new year, and keep you informed about relevant trends and developments that may impact compliance considerations associated with your business activities.
Authored by Heidi Gertner, Susan Lee, and Meredith Manning
