Sprout Pharmaceuticals, Inc.

The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) has reviewed a promotional communication, a social media post (post)1 regarding ADDYI (flibanserin) tablets, for oral use (Addyi). The FDA Bad Ad Program also received complaints regarding this post. The post by Sprout Pharmaceuticals, Inc.’s (Sprout) Chief Executive Officer (CEO), Cindy Eckert2, on the Instagram account, “cindypinkceo,” is false or misleading in that it makes representations about the benefits of Addyi but fails to include any risk information about the drug and omits material information regarding the full indication, including the limitations of its use. Thus, the post misbrands Addyi within the meaning of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and makes its distribution violative. 21 U.S.C. 352(a), (n); 321(n); 331(a). See 21 CFR 202.1(e)(3)(ii) and (iii); (e)(5). In addition, this material was not submitted at the time of initial dissemination or publication as required by 21 CFR 314.81(b)(3)(i). These violations are concerning from a public health perspective because the promotional communication creates a misleading impression regarding the safety and effectiveness of Addyi, a drug with a number of serious risks, including a boxed warning due to the risk of severe hypotension and syncope in certain settings.

Below are the indication and summary of the most serious and most common risks associated with the use of Addyi3. According to the INDICATIONS AND USAGE section of the FDA-approved product labeling (PI):

ADDYI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

A co-existing medical or psychiatric condition,

Problems within the relationship, or

The effects of a medication or other drug substance.

Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.

ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men.

ADDYI is not indicated to enhance sexual performance.

The PI for Addyi contains a boxed warning regarding severe hypotension and syncope in certain settings. Addyi is contraindicated in patients using concomitant moderate or strong CYP3A4 inhibitors, in patients with hepatic impairment, and in patients with known hypersensitivity to Addyi or any of its components. The PI for Addyi includes warnings and precautions regarding hypotension and syncope due to an interaction with alcohol, hypotension and syncope with CYP3A4 inhibitors, central nervous system depression, hypotension and syncope with Addyi alone, syncope and hypotension in patients with hepatic impairment, hypersensitivity reactions, and mammary tumors in female mice. The most common adverse reactions reported with Addyi are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.

OPDP notes that the Warning Letter dated August 31, 2020, sent to Sprout addressed presentations for Addyi with certain similarities to the post addressed in this letter. In the August 31, 2020, Warning Letter, OPDP noted that a radio ad for Addyi omitted important risk information and omitted material information regarding Addyi’s indication, including its limitations of use, thus creating a misleading impression about the safety and approved use of the drug. OPDP is concerned that, despite receiving this previous Warning Letter, Sprout continues to promote Addyi in a similarly misleading manner.

Prescription drug advertisements and labeling (promotional communications) misbrand a drug if they are false or misleading with respect to risk. The determination of whether a promotional communication is misleading includes, 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 facts 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 in the promotional communication.

The post is misleading because it includes representations about the benefits of Addyi but fails to communicate any risk information. For example, the post includes the following:

“The first articles on @addyi a decade ago questioned the women struggling, told them it was normal, debated how many more satisfying sexual events were enough for them to deserve a pill…” (user generated text)

“…Addyi, the Sex Pill for Women…” (screenshot)

“Addyi is the first FDA-approved treatment for women’s sexual dysfunction.” (screenshot)

The post, however, entirely omits risk information. By omitting the risks associated with Addyi, the post fails to provide material information about the consequences that may result from the use of Addyi and creates a misleading impression about the drug’s safety. This omission is especially problematic from a public health perspective given the serious risks associated with the drug.

The post is misleading because it fails to provide material information regarding Addyi’s full FDA-approved indication, including important limitations of use. Specifically, the INDICATIONS AND USAGE section of the PI states the following (underlined emphasis added):

ADDYI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

A co-existing medical or psychiatric condition,

Problems within the relationship, or

The effects of a medication or other drug substance.

ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men.

ADDYI is not indicated to enhance sexual performance.

By failing to disclose the full indication and limitations of use associated with Addyi, the post creates a misleading suggestion about the FDA-approved indication and use for Addyi. Addyi is approved only for use in premenopausal women with acquired, generalized HSDD. The indication further limits the use of the drug to the treatment of premenopausal women with acquired, generalized HSDD that is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance.

Additionally, the post fails to disclose Addyi’s limitations of use, including that it is not indicated for the treatment of HSDD in postmenopausal women or men, and that it is not indicated to enhance sexual performance. This is especially concerning given the unqualified representation made in the post suggesting that Addyi is the “sex pill for women.” This broad claim suggests that Addyi is indicated, among other things, to enhance sexual performance, which is particularly concerning given the limitations of use and serious risks of this product.

FDA regulations require any labeling or advertising devised for promotion of the drug product to be submitted at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product. Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. A copy of the post was not submitted to OPDP under cover of Form FDA-2253 at the time of initial dissemination or publication as required by 21 CFR 314.81(b)(3)(i).

For the reasons discussed above, the post misbrands Addyi within the meaning of the FD&C Act and make its distribution violative. 21 U.S.C. 352(a), (n); 321(n); 331(a). See 21 CFR 202.1(e)(3)(ii) and (iii); (e)(5). Furthermore, Sprout did not comply with 21 CFR 314.81(b)(3)(i).

This letter notifies you of our concerns and provides you with an opportunity to address them. OPDP requests that Sprout cease any violations of the FD&C Act. Please submit a written response to this letter within 15 working days from the date of receipt, addressing the concerns described in this letter, listing all other promotional communications (with the 2253 submission date) for Addyi that contain representations such as those described above, and explaining your plan for the timely discontinuation of such communications, or for ceasing distribution of Addyi.

Failure to adequately address this matter may lead to regulatory action. If you believe that your product is not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter.

Additionally, we request that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective communication(s) about the concerns discussed in this letter. The corrective communication(s) should be disseminated to the audience(s) that received the promotional communication identified in the opening paragraph of this letter. OPDP recommends that corrective communication(s) include a description of the promotional communication identified in this letter, which misbrands Addyi; include a summary of the concerns described in this letter; and provide information to correct each of these concerns. Corrective communication(s) should be free of promotional claims and presentations. To the extent possible, corrective communication(s) should be distributed using the same media, and generally for the same duration of time and with the same frequency as the promotional communication identified in the opening paragraph of this letter.

The concerns discussed in this letter do not necessarily constitute an exhaustive list of potential violations. It is your responsibility to ensure compliance with each applicable requirement of the FD&C Act and FDA implementing regulations.

Please direct your response to the undersigned at the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266. A courtesy copy can be sent by facsimile to (301) 847-8444. Please refer to MA 493 in addition to the NDA number in all future correspondence relating to this particular matter. All correspondence should include a subject line that clearly identifies the submission as a Response to Warning Letter. You are encouraged, but not required, to submit your response in eCTD format. All correspondence submitted in response to this letter should be placed under eCTD Heading 1.15.1.6. Questions related to the submission of your response letter should be emailed to the OPDP RPM at CDER-OPDP-RPM@fda.hhs.gov.