Lizzo has Thoughts: First Untitled Letter for Promotional Activities in a YearJune 14, 2023
After about a year without any untitled letters from OPDP, Xeris Pharmaceuticals received an untitled letter for their promotion for Recorlev (levoketoconazole) for misleading safety and efficacy claims. To quote everyone’s favorite flautist (and TikTok sensation) Lizzo, “it’s about d@mn time!” (Sorry for the bowdlerization, but we’re trying to make it past everyone’s filter and HR warned us in any event.)
MISLEADING PRESENTATION OF RISK INFORMATION
Recorlev is a drug for endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or was not curative. It has boxed warnings for hepatoxicity and QT prolongation and is contraindicated in numerous patient populations and has 17 adverse reactions with an incidence of >20%. In other words, this is a drug that requires serious risk information to be presented.
Apparently, however, Xeris treated Recorlev as if it was “fabulous” (sorry Lizzo, we’ll stop, we promise) and merely noted that monitoring was important for patients on Recorlev and that “Side effects can occur with Recorlev, including some that are serious.” FDA took issue with that presentation considering that the product has boxed warnings for hepatotoxicity and QT prolongation which can cause death. Moreover, the presentation of risk information suggested that monitoring would be sufficient to help patients avoid these potentially fatal adverse events. Would that it were so! But alas, FDA didn’t think this presentation of risk information was appropriate. This is so even though elsewhere on the webpage the risk information was presented in the “INDICATION AND IMPORTANT SAFETY INFORMATION” section. But the presentation did not mitigate the misleading effect of the “Monitoring and side effects” presentation because the boxed warnings were buried in the middle of a consolidated risk section.
MISLEADING CLAIMS ABOUT EFFICACY
On top of the misleading presentation of risk information, which would have been enough for a letter in our opinion, Xeris was apparently feeling fussy, walkin’ in [their] Balenci-ussy’s, tryna bring out the fabulous and made misleading claims about efficacy (sorry, we will stop quoting Lizzo, don’t take our blog away). Without getting too complicated with numbers (we were promised there was no math in law), Xeris played fast and loose with the clinical trial data by inflating the numbers of who benefitted from Recorlev, such as claiming that 52% of patients had normal cortisol levels at the end of the trial without disclosing that more than half the patients had dropped out of the study due to adverse events or lack of efficacy. Moreover, they tried to imply that 67% of patients who moved on to the second part of one of their studies had normal cortisol levels by the end of the study. Which would be true, if one defined “end of the study” as “the end of the titration phase and we’ll ignore the other two phases of the study that would actually get us to the end of the study.”
First, as should be clear, these bloggers should never be trusted with pop culture. We will only ruin it. Second, as we have been stating for years (decades at this point), Important Safety Information (ISI) is not sufficient to present risk information and accurate risk information needs to be presented in the context of the main presentation. An accurate summary in the ISI is not necessarily going to save an inadequate presentation of risk and safety information in the body of the promotional piece, especially if that presentation is itself inaccurate or misleading.
Lastly, and we’re unsure why this requires repeating, and yet, here we are, don’t mess with the clinical trial numbers. The reviewers at FDA (unlike your loyal bloggers) are pretty good with numbers and can read the prescribing information. They know when you’re juking the stats. We’ve blogged on this previously almost exactly a year ago (we did a slightly better job on not offending pop culture). Interestingly, in both instances, FDA’s Untitled Letters lead with the allegations about misleading efficacy claims and focus on the numbers presented.
This letter ticks several boxes regarding FDA priorities for enforcement – Xeris launched Recorlev in 2022 and it is a drug with significant risks.
In summary, stick to the basics – present safety information accurately and in the body of the presentation and don’t play around with the numbers and then turn up the music, turn down the lights, [we] got a feelin’ [we’re] gonna be alright.