By Sarah Wicks & Dara Katcher Levy —
FDA’s Office of Prescription Drug Promotion (OPDP) has issued its fourth Untitled Letter of 2024 – this one to AbbVie, Inc. (AbbVie), for a direct-to-consumer (DTC) TV advertisement for its drug UBRELVY (ubrogepant) that features tennis star, social media influencer and entrepreneur Serena Williams. This letter, dated August 29, 2024, (at the height of the US Open, no less) comes not even a month after OPDP’s last letter from August 1, and a little over a month since another celebrity-related Untitled Letter, both of which we blogged about here. OPDP alleges in this latest letter that the DTC TV ad made false or misleading representations and suggestions about the efficacy of UBRELVY, which is considered misbranding of the product under the Federal Food, Drug, and Cosmetic Act. Advantage, OPDP.
UBRELVY is indicated for the acute treatment of migraine with or without aura in adults and is not indicated for the preventive treatment of migraine. The approved labeling for UBRELVY includes a warning and precaution regarding hypersensitivity reactions, with the most common adverse reactions being nausea and somnolence.
The Untitled Letter states that the TV ad misleadingly suggests that UBRELVY provides a greater benefit in treating migraines than what has been demonstrated in clinical trials, which, from a public health perspective, can mislead healthcare providers, patients, and caregivers. Specifically, OPDP alleges the ad implies that UBRELVY quickly eliminates migraine pain after just one dose, which was not fully supported by clinical data. The TV ad shows Serena preparing to appear on a talk show and holding her head while experiencing pain and light sensitivity from a migraine headache, and then almost immediately appearing relaxed while the show lights continue to shine overhead. Serena then voice overs with the claim that “One dose works fast to eliminate migraine pain,” with an accompanying graphic, “UBRELVY QUICKLY ELIMINATES MIGRAINE PAIN,” (emphasis added). OPDP claims this before-and-after presentation, together with the claims, misleadingly suggest that UBRELVY eliminates migraine pain and symptoms more quickly than demonstrated in clinical trials, where only 19%-21% of patients experienced complete pain freedom within two hours of taking 50 mg and 100 mg of the drug, respectively, meaning the majority did not see such results. Conversely, 11.8% of placebo patients achieved pain freedom at two hours. OPDP acknowledged the claim, “Some people had pain freedom within 2 hours” appeared in a small footnote in the TV, but this was not sufficient to mitigate the misleading suggestion that UBRELVY can eliminate migraine pain and symptoms more quickly than has been demonstrated in clinical trials. OPDP also states that the “One dose…” language misleadingly suggests that all patients who take UBRELVY can expect their migraine pain to be eliminated after a single dose, when this also has not been demonstrated in clinical trials. According to the labeling, approximately 19% to 22% of patients achieved pain freedom at two hours after receiving one dose of UBRELVY, which means that 78% to 81% of patients were not pain-free after one dose. OPDP also specifically notes that the DOSAGE AND ADMINISTRATION section of the labeling for UBRELVY says, “If needed, a second dose may be taken at least 2 hours after the initial dose,” (emphasis added), adding to the misleading nature of the TV ad.
There are a few really interesting points that come with this letter, and we have to wonder whether OPDP is playing a few head games with this migraine drug ad.
The first issue of note is that the Untitled Letter asserts that using a celebrity athlete of Serena Williams’s stature amplifies the misleading impact of the ad to the audience due to her perceived credibility. The statement includes a footnote with a string of references dating back to 1979 to support the assertion. While not a new concept, OPDP did not include such a reference in the recent Auvi-Q enforcement letter featuring Brittany Mahomes, nor has OPDP included such a claim in other enforcement letters addressing ads featuring celebrities and athletes over the past few years. These bloggers are curious to see whether OPDP may be taking a page from the FTC regarding concerns over endorsements and whether OPDP may extend this analysis beyond traditional celebrities featured in TV ads to social media influencers with large followings.
Another point of interest is contained in footnote 6. OPDP acknowledges that the storyboard submitted on Form 2253 identifies in frame one that the ad opens in the afternoon with Serena in a talk show dressing room experiencing migraine pain and by frame eight of the storyboard, when Serena does her final mirror check before heading out to the talk show, it is evening – indicating a several hour time lapse between when UBRELVY is taken and when it starts to work. OPDP notes that the time lapse is lost on the audience viewing the TV ad as the ad does not otherwise indicate the passing of time in a manner consistent with the storyboard. For promotional committee reviewers, this really drives home the point that even with an OPDP pre-review of a DTC TV ad storyboard, the implementation of that storyboard will drive the compliance status of the ad. While a number of scene changes may be captured in a storyboard, there are other aspects of a finished TV ad that must be considered (here – how lapse of time should be represented – but in other cases, quick movements and competing audio, among other things).
The Untitled Letter also references OPDP advisory comments previously provided to the prior holder of the UBRELVY New Drug Application (NDA) (Allergan, Inc.) on March 10, 2020. OPDP states that while Allergan is no longer the application holder, “OPDP is concerned that [AbbVie] appears to be promoting Ubrelvy using similar claims and presentations in a misleading manner.” New sponsors take note – when acquiring a new drug from another company, GET THE REGULATORY CORRESPONDENCE.
Game, set and match – it’s unclear whether AbbVie’s implementation of the storyboard was an unforced error or whether OPDP’s interpretation is something of a wildcard. What we can tell you is that TV ads featuring drugs for conditions that affect millions of Americans will always be a higher priority for OPDP, and the stakes are high to get these ads right.
