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FDA warns Sprout for misleading Addyi come-on

Posted 15 September 2020 | By Kari Oakes 

FDA warns Sprout for misleading Addyi come-on

Sprout Pharmaceuticals’ promotion of Addyi both mischaracterizes the drug’s indication and downplays potential serious adverse events associated with its use, according to a warning letter from the US Food and Drug Administration (FDA).
Sprout Pharmaceuticals markets the non-hormonal drug Addyi (flibanserin) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. To meet HSDD criteria, low desire must cause marked distress or interpersonal difficulty and not be attributable to medical, psychiatric, or social problems.
In the warning letter dated 31 August 2020, FDA’s Office of Prescription Drug Promotion (OPDP) takes issue with radio advertisements for Addyi. The radio spot in question begins with an alert: “Listen up! Sexual dysfunction isn't just a ‘man’ thing.” The announcer goes on to note that one in 10 premenopausal women “suffer from frustrating low libido, also known as HSDD. That’s a lot of women in your cycle class just spinning their wheels.”
The radio ad characterizes Addyi as “an FDA-approved pill for women frustrated by their low libido,” and details how to access the firm’s website for a medical consultation, and how to get the drug with no out-of-pocket costs.
Addyi comes with a boxed warning for the hypotension and syncope risks, and FDA noted in the warning letter that though the radio ad mentions the risk of “low blood pressure and fainting in certain settings,” the ad still “fails to disclose material information from the Boxed Warning that the use of Addyi and alcohol together close in time increases the risk of severe hypotension and syncope.” Details about increased risk with certain medications and for those with liver problems were also omitted from the radio spot, said the agency.
“By failing to adequately communicate the indication and limitations of use associated with Addyi, the radio ad creates a misleading impression about the FDA-approved indication,” said the warning letter. “This is particularly concerning given the serious risks of this product and the suggestion that Addyi is approved for all women ‘frustrated by their low libido’ when this is not the case.”
The warning letter calls for Sprout to stop the activities OPDP considers to be misbranding, and to provide a list of all other promotional materials that contain similar statements. “Because the violations described above are serious,” says the agency, Sprout’s response should include a comprehensive plan for truthful, non-misleading, and complete corrective messages for the audience affected by the violative material.
Currently, Addyi’s Facebook page and Instagram account feature memes with messages such as “less time in the streets/more time in the sheets” with accompanying text that reads, “Say 'BUH BYE' ✌️ to frustrating low libido, also known as HSDD. A better sex life is possible and proven. Addyi is an FDA-Approved Little Pink Pill for Premenopausal Women Frustrated by Their Low Libido.” Patient labeling information scrolls beneath the meme and the viewer is advised to consult full prescribing information.

Addyi Instagram post, accessed 15 September 2020.

Approval history
Addyi was approved by FDA in August 2015 after two prior unsuccessful attempts. The agency’s decision followed a favorable 18-6 vote when the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee met jointly earlier that year to consider approving Addyi. (Related: Developing the next female Viagra? FDA offers draft guidance with caveats, Regulatory Focus, 25 October 2016)
After the approval, FDA officials sketched out their thinking In a New England Journal of Medicine article. “In the face of divergent views, we at the FDA think it’s important to clarify why flibanserin was approved after being rejected twice,” said Hylton Joffe, MD, then-director of FDA’s Division of Bone, Reproductive and Urologic Products, as senior author of the commentary. Joffe now serves as the acting director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine.
The initial data presented for Addyi’s approval showed a concerning benefit-risk profile, with risks for hypotension and syncope, especially when the drug was taken with alcohol. Risks were also enhanced with moderate or strong inhibitors of cytochrome P-450.
Efficacy was modest in clinical trial data, but there had been no prior pharmacologic treatment for the relatively recently defined disease entity of HSDD. The contentious process leading up to the hearing had proponents of approval as well as those opposing Addyi accusing the other side of gender bias. In the perspective piece, Joffe and his collaborators noted that some criticism came from Even the Score, “an advocacy campaign partly funded by Sprout Pharmaceuticals, flibanserin’s sponsor after Boehringer Ingelheim sold the rights to the drug.”
Post-marketing review
The eventual approval came with a risk evaluation and mitigation strategy (REMS), as well as requirements for post-marketing surveillance and a boxed-warning alerting patients to the risks of syncope and severe hypotension. The boxed warning was revised in 2019 after post-marketing data showed that alcohol need not be completely avoided, but should be stopped 2 hours before the bedtime dose of the drug, which is meant to be taken chronically. Sprout had asked for complete removal of the boxed warning and any mention of alcohol being contraindicated, according to the FDA announcement. (Related: FDA softens stance on drinking with female libido drug, Regulatory Focus, 12 April 2019)


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