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FDA Advertising and Promotion Enforcement Activities: Update

October 12, 2020, Covington Alert

This e-alert is part of a series of e-alerts summarizing publicly available FDA enforcement letters (i.e., warning letters and untitled letters) relating to the advertising and promotion of prescription drugs, medical devices, and biologics.

In September, the Office of Prescription Drug Promotion (OPDP) posted three warning letters on FDA’s website, including one letter issued in August:

  • Warning Letter to Sprout Pharmaceuticals, Inc. re: NDA 022526 ADDYI® (flibanserin) tablets, for oral use, MA 241 (Aug. 31, 2020) (Addyi Warning Letter)
  • Warning Letter to Nalpropion Pharmaceuticals LLC re: NDA 200063 CONTRAVE® (naltrexone hydrochloride and bupropion hydrochloride) extended-release tablets, for oral use, MA 516 (Sept. 22, 2020) (Contrave Warning Letter).
  • Warning Letter to Nephron Pharmaceuticals Corporation re: ANDA 78202 Budesonide Inhalation Suspension, for inhalation suspension, MA 1, 3 (Sept. 22, 2020) (Budesonide Warning Letter).

The above letters represent the third, fourth, and fifth enforcement letters OPDP has issued this year. The Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) and the Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) did not post any enforcement letters related to advertising and promotion in September. FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) has not yet posted any enforcement letters in 2020.

This alert merely summarizes the allegations contained in FDA’s letters.It does not contain any analyses, opinions, characterizations, or conclusions by or of Covington & Burling LLP.  As a result, the information presented herein does not necessarily reflect the views of Covington & Burling LLP or any of its clients.

Office of Prescription Drug Promotion (OPDP)

Addyi Warning Letter (August 2020)

OPDP’s warning letter to Sprout Pharmaceuticals, Inc. (Sprout) states that a direct-to-consumer radio advertisement misbrands Addyi, a product indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).OPDP alleges that the advertisement makes false or misleading claims about the drug’s risks and omits other material facts. It further states that the violations “are concerning from a public health perspective because they create a misleading impression about the safety and effectiveness of Addyi, a drug that bears a Boxed Warning due to the risk of severe hypotension and syncope in certain settings.”

The warning letter notes that OPDP provided advisory comments in 2016 to VALEANT Pharmaceuticals, International, Sprout’s former parent company. It explains, “We are concerned that, in the radio ad, Sprout is continuing promotion of Addyi in a manner that does not adequately convey the FDA-approved indication nor the important risk information for the drug.”

False or Misleading Risk Presentations

OPDP alleges that the advertisement is misleading because it omits information on risks associated with Addyi. OPDP states that the advertisement “includes numerous claims and presentations regarding the benefits of using Addyi.” Yet, the advertisement allegedly omits (1) “all the contraindications associated with the use of Addyi” (emphasis by OPDP); (2) “material information” from the Boxed Warning regarding the increased risk of severe hypotension and syncope when Addyi is taken together with alcohol, with certain prescription medications, and among patients with liver problems;[1] and (3) warnings and precautions regarding central nervous system depression, as well as hypotension and syncope associated with the use of Addyi alone.

Omission of Material Facts

OPDP alleges that claims in the advertisement “create a misleading impression regarding the scope of the approved use of Addyi.” Specifically, the advertisement includes the following claims:

  • “1 in 10 premenopausal women suffer from frustrating low libido, also known as HSDD.”
  • “Meet Addyi – the first and only FDA-approved non-hormonal pill for acquired, generalized HSDD in premenopausal women. In other words: An FDA-approved pill for women frustrated by their low libido.”
  • “Ladies, add your desire back with Addyi.”

OPDP states that these claims are concerning because they “suggest[] that Addyi is approved for all women ‘frustrated by their low libido’ when this is not the case.”  OPDP references the Addyi Medication Guide, which states that Addyi is used to treat women “who have low sexual desire no matter the type of sexual activity, the situation, or the sexual partner” and that “ADDYI is not for use to improve sexual performance” (emphasis by OPDP).

Contrave Warning Letter (September 2020)

OPDP’s warning letter to Nalpropion Pharmaceuticals LLC (Nalpropion) states that a Google sponsored link misbrands Contrave, a weight management product with a Boxed Warning regarding the risk of suicidal thoughts and behaviors. FDA received a complaint about the sponsored link through its Bad Ad Program. The letter further states that, in 2017, OPDP issued an Untitled Letter to Orexigen Therapeutics, Inc., the former application holder, regarding a television advertisement for Contrave that “omitted important risk information.”

The warning letter provides the following additional commentary from OPDP: “Obesity and excessive weight are significant public health concerns that affect millions of adults in the United States and are associated with numerous co-morbidities. Consumers and patients who seek assistance with their weight-loss goals should not be misled regarding the serious risks, expected benefits, and necessary nutritional and lifestyle modifications associated with the use of a weight management prescription drug product, such as Contrave.”

False or Misleading Risk Presentation

OPDP alleges that the sponsored link is misleading because it presents efficacy claims but “fails to communicate any risk information” (emphasis by OPDP).Specifically, OPDP points to the following claims (emphasis in original):

  • CONTRAVE® Weight Loss - (naltrexone HCl/bupropion HCl)
  • “Lose 2-4x more weight on average than with diet and exercise alone!”

OPDP acknowledges that the sponsored link includes the statement “View Important Safety Info & Boxed Warning,” but it adds that “this statement does not mitigate the misleading omission of risk information.” According to OPDP, “This misleading presentation is particularly alarming from a public health perspective given that the sponsored link utilizes claims that could appeal to patients who seek assistance with their weight-loss goals, but fails to communicate that Contrave is associated with serious and potentially life-threatening risks, such as those contained in the boxed warning that describes the risk of suicidal thoughts and behaviors.”

False or Misleading Claims about Efficacy

OPDP alleges that the sponsored link is misleading with respect to efficacy because it fails to communicate material information from the full FDA-approved indication regarding (1) the use of Contrave as an adjunct to diet and exercise, (2) initial BMI criteria, (3) the requisite presence of weight-related comorbid condition(s) among a subset of patients for whom the drug is indicated, and (4) the limitations of use. OPDP states that the claims cited above “misleadingly imply that patients, no matter their BMI, should expect to achieve the ‘average’ results presented in the sponsored link.”OPDP states that the phrase “than with diet and exercise alone!” does not adequately convey that a calorie-reduced diet and increased physical activity are “necessary” to achieve the benefits stated in the PI.

Additionally, OPDP alleges that the sponsored link is misleading because it references the more favorable co-primary endpoint of percent change from baseline body weight. But the advertisement does not disclose that the percentage of patients who achieved a treatment response (i.e., at least five percent weight loss from baseline in one year) was 36 to 57 percent with Contrave compared to 17 to 43 percent with placebo. “Without this context,” OPDP states, “the presentation could be read to suggest that any amount of weight loss (i.e., 2-4x) was considered clinically meaningful for Contrave.”

Budesonide Warning Letter (September 2020)

OPDP’s warning letter to Nephron Pharmaceuticals Corporation (Nephron) states that emails sent by the CEO and a company sales representative misbrand Budesonide Inhalation Suspension (Budesonide).OPDP alleges that the emails suggest that Budesonide, an asthma medication, is intended for the treatment of symptoms associated with “Coronavirus Disease 2019” (COVID-19), a new use for which the product lacks approval and for which the labeling does not provide adequate directions for use. OPDP further states that the emails omit risk information about the drug. The emails were submitted as complaints to the Bad Ad Program. 

Lack of Adequate Directions for Use

OPDP alleges that claims and representations in the emails create a misleading impression that Budesonide is safe and effective as a treatment for symptoms associated with COVID-19, even though Budesonide is not approved for such use and its labeling does not contain adequate directions for such use. Specifically, OPDP alleges:

  • On July 14, 2020, the CEO sent an email containing the following headline claim in conjunction with an image of the product and “what appears to be SARS-CoV-2”: “BUDESONIDE RELIEVES RESPIRATORY SYMPTOMS ASSOCIATED WITH COVID-19” (emphasis in original). The email further states, “Over the last few weeks, doctors and researchers have touted the benefits of using Budesonide as a treatment for symptoms associated with COVID-19. One physician, who went viral this month [sic], called Budesonide a ‘silver bullet.’”
  • On July 7, 2020, the sales representative sent an email with the subject line “COVID-19 – Budesonide – Video. ”The email includes a link to a YouTube video, which the sales representative says depicts a physician discussing “treating COVID patients successfully with Budesonide and an antibiotic. "The email further states, “You may want to share this with your respiratory team and pulmonary docs. Cost effective way to treat Coronavirus!” 

OPDP states that these claims and representations “are particularly alarming from a public health perspective because COVID-19 has caused significant morbidity and mortality, and because there is currently no FDA-approved treatment for symptoms associated with COVID-19.”

False or Misleading Risk Presentation

OPDP alleges that the emails misbrand Budesonide because they include claims and representations about the drug’s uses and/or benefits but “fail to communicate any risk information about the product” (emphasis by OPDP).Consequently, the promotional materials “create a misleading impression” about the drug’s safety.

If you have any questions concerning the material discussed in this client alert, please contact the following members of our Food, Drugs, and Devices practice.

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[1] OPDP acknowledges that the advertisement “presents some risk information from the Boxed Warning” regarding low blood pressure and fainting.H owever, OPDP states that the advertisement “omits material information pertaining to these risks.”


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