Fake News? Fantastic Claims and Where to Find Them (or Where FDA Will)

With our second OPDP enforcement letter of 2022, FDA is making one thing clear: OPDP will find your promotional content—even when it may not look like promotional content.  While it’s not mind-blowing that OPDP would find a series of videos while scrolling Instagram (particularly when it’s flagged by FDA’s Bad Ad program), OPDP issued a Warning Letter on February 11 concerning a little-seen interview with the former CEO of CytoDyn discussing its investigational new drug product, leronlimab.  Let’s be clear here: the statements CytoDyn made about leronlimab in the interview are outrageous (more on that below)—that FDA found them problematic is not the interesting part.  What is interesting is that the video appeared on the YouTube channel of “one of the fastest growing financial media portals in the world,” and the link to the video on the cytodyn.com website was included under an “In the News” page.  At first blush, we were deja vu-ing all over again to FDA’s action against Aegerion back in 2013.  But the CytoDyn interview was different.

Proactive, the company behind the YouTube Channel that included the CytoDyn video, describes itself as “enabl[ing] companies and investors to connect intelligently.”  Proactive’s Terms and Conditions includes the following statement:

In exchange for publishing services rendered by the Company on behalf of any issuer named on the Site, including the promotion by the Company of the issuer in any Content on the Site, the Company receives from said issuer annual aggregate cash compensation in an amount equal to Twenty Five Thousand dollars ($25,000).

FDA notes this point in Footnote 1 of the Warning Letter, calling out the video and Proactive with the quote, “Proactive is a publisher and receives compensation for publishing content on this account for and on behalf of its clients.”  This footnote call-out may be easily missed, but it is critically important for FDA in establishing that the objectionable content is, in fact, promotional content that may be separate and apart from “the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media.”  21 C.F.R. §312.7.

This is not the first time FDA has admonished CytoDyn’s communications about leronlimab.  While not an OPDP enforcement letter, FDA took the rare step to publicly criticize the company last year for its communications about leronlimab.  At that time, FDA stated,

CytoDyn has publicly communicated differences in small subgroups from the CD12 trial (e.g., a sub-group analysis of 62 of the 394 patients studied) suggesting that the data demonstrated a mortality benefit in certain patients who had received leronlimab. Subgroup analyses have well-established limitations, especially in the context of a clinical trial that has failed to show a benefit in the overall study population. For example, subgroups are often small, and therefore imbalances are common. Here, the data from CD12 illustrated imbalances in mortality among subgroups, some favoring leronlimab and some favoring placebo. None of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons. However, as noted above, such analyses may inform the design of future clinical trials investigating leronlimab for the treatment of COVID-19.

FDA may have taken this unusual step out of concerns that CytoDyn’s communications were not traditionally “promotional” and an OPDP Warning or Untitled Letter might not be appropriate.  After FDA’s public criticism, DOJ and the SEC subpoenaed the company and its executives seeking documents and information related to CytoDyn’s public statements about leronlimab.  According to Fierce Biotech, these investigations were disclosed in an SEC filing dated July 30.

The video that is the subject of the February 2022 OPDP Warning Letter, dated September 22, 2021, features an interview with then-CEO of CytoDyn, Dr. Nader Pourhassan.  The video, created four months after FDA’s public criticism of the company for communications about subgroup data on leronlimab and almost two months after the company announced it had received subpoenas from DOJ and SEC, shows Dr. Pourhassan again discussing leronlimab subgroup data from the same studies to which FDA previously objected.

As part of the discussion of leronlimab data in the sponsored video, Dr. Pourhassan describes a study that missed its primary and secondary endpoints as follows: “In the United States, we did a trial of 394 patients which included severe and critically ill population. In the critically-ill population, our results were really strong. . .”  He further describes a subgroup analysis as “Our critically-ill population [study] that we did in the United States when we gave a dose of leronlimab, the survival rate was 78%. Once we gave them another dose, the survival rate went up to 82%.”  Dr. Pourhassan asks the audience to “[I]magine, if 78% went to 82, the next one would be maybe 88, and then 95.”  He admits that he is “making up numbers,” but he hypothesizes that “if [study results] just follows the same pattern what we learned, this is going to be the most fantastic results anybody could ever imagined to have.”  He ends with the disclaimer “Now I’m not saying that’s what we’re going to get, but I’m saying that’s what the results are showing.”

Based on the nature of the sponsored interview, FDA concluded that the video is false and misleading and promotes leronlimab as safe and effective for the purposes for which it is being investigated.  Specifically, FDA explains “the video is extremely concerning because it significantly mischaracterizes the clinical trial data for leronlimab in the treatment of COVID-19, and the stated conclusions based on this mischaracterized data create a misleading impression regarding the safety and efficacy of the product.”  FDA therefore requests that CytoDyn disseminate corrective communications about these studies.

Typically, when corrective advertising is requested as part of an OPDP Warning Letter, the corrective advertising takes place in the same medium, directed toward the same audience, as the original violative communication.  Will we see more “Fake News” interviews with corrective information about leronlimab?  If so, Proactive Media may be the real winner in all of this.

Aside from the obvious lessons here (e.g., don’t call subgroup analyses from failed studies “really strong” results), it’s important to consider the different approaches taken by FDA based on the types of communications.  FDA’s initial approach was to correct misinformation through a public statement—sending an OPDP Warning Letter only when the communications could more clearly be tied as “promotional.”  And FDA did its research—it called out Proactive Media’s platform as a sponsored publication.  Given the rise in sponsorship “opportunities” on news platforms, and FDA’s interest in sponsored news segments, companies should be treating these opportunities the same way they would treat more traditional promotional communications and ensure truthful communications.