On March 31, 2022, the Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) issued an untitled letter to Bausch Health Companies Inc. regarding a promotional video and healthcare professional website for DUOBRII™ (halobetasol proprionate and tazarotene) lotion, indicated for topical treatment of plaque psoriasis in adults (DUOBRII). The video[1] content aired on a popular television network and the website[2] content was directed at healthcare professionals. This is only the second untitled letter from OPDP this year, both of which were focused on false and misleading promotional messaging.
DUOBRII is contraindicated in pregnancy and contains warnings and precautions in its FDA-approved product labeling (PI) regarding embryofetal risk, hypothalamic-pituitary-adrenal (HPA) suppression and other systemic glucocorticoid effects, local adverse reactions, photosensitivity and risk for sunburn, ophthalmic adverse reactions and concomitant skin infections.
FDA wrote that, for the reasons discussed below, the video and website i) create a false and misleading impression regarding the overall benefit of DUOBRII treatment and ii) raise concerns from a public health perspective due to a failure to include information about serious systemic risks and serious skin reactions. In the letter, FDA referred to a letter sent to Bausch in February 2020 for DUOBRII in which it expressed similar concerns.
This is the second untitled letter FDA has sent this year. In January, FDA sent an untitled letter to Eli Lilly & Company regarding promotional claims for TRULICITY® conveyed in social media.
Minimization of Risks: The FDA letter states that the video minimized risks associated with DUOBRII:
- Pregnancy: A woman appearing to be of reproductive age with two young children states that she uses DUOBRII frequently and often in the case where she has a flare up of her psoriasis.
- There was no recitation of the warning and precaution section of the PI advising pregnant females to obtain a pregnancy test within 2 weeks prior to initiation of DUOBRII therapy and to use effective contraception during treatment.
- The woman’s claim[3] that she uses DUOBRII often when she experiences a flare up is misleading in that it suggests that a female of reproductive age can initiate the product or use it whenever experiencing a flare up without regard to the need for pregnancy testing or birth control.
- Sunlight sensitivity: A woman is outside, with shoulders and arms exposed, discussing how she needed to wear long sleeve shirts “even when it was warm” to hide her psoriasis and touting the success of her treatment.
- There were no warnings and precautions from the PI about photosensitivity and the need for use of sunscreen and protective clothing.
- Other Warnings and Precautions:
- There was no mention of ophthalmic adverse reactions.
- Important risk information about HPA-axis suppression and other systemic glucocorticoid effects was presented in small font at the bottom of the screen. In contrast, efficacy claims were prominently presented in large print and simultaneously narrated in the audio portion of the video.
False and Misleading Claims: FDA warned of false and misleading claims, including:
- First and Only: The physician spokesperson in the video refers to DUOBRII as the “first and only” topical that combines two active ingredients, both with anti-inflammatory benefits that limit plaque growth.
- FDA noted that there are other topical combination products for treatment of plaque psoriasis that were approved prior to DUOBRII.
- Clinical Superiority: The patient spokesperson in the video speaks about failing prior treatments and how DUOBRII was better than other creams, suggesting clinical superiority over other treatments.[4]
- There are no studies that demonstrate DUOBRII is superior to other plaque psoriasis products on the market or that DUOBRII has been shown effective in patients who failed to respond to other plaque psoriasis treatments
- While the video did include a superscript indicating that “individual results may vary” and FDA acknowledged that “these claims may be an accurate reflection of the spokesperson’s own experience”, FDA noted that was not enough to mitigate any misleading impressions of clinical superiority.[5]
- Efficacy and Mechanism of Action: The website includes claims of “demonstrated synergy” and “superior efficacy” of DUOBRII versus the aggregated results of two monotherapies. These claims are based on data derived from post hoc analyses of a single phase 2 trial, of limited sample size, which compared Duobrii separately to its individual components and vehicle.
- The phase 2 trial was not designed to support conclusions comparing the superior efficacy of DUOBRII to its aggregated components.
- The efficacy data presented overstated the efficacy of DUOBRII.
In past years, FDA enforcement has been focused on promotional messaging that omits and/or minimizes important risk information. This year, it appears that FDA enforcement efforts are right on track, and FDA is also making clear that so-called “consistent with label” messaging (i.e., the efficacy and mechanism of action section) must be accompanied with the appropriate context as described by FDA in its June 2018 Final Guidance.
[1] Storyboard available here: https://www.fda.gov/media/157590/download .
[2] Screenshot available here: https://www.fda.gov/media/157589/download; revised full site available here: https://www.duobrii.com/hcp/efficacy.
[3] Specifically, the woman states “I’ve been using DUOBRII for 2 years, it works into my routine. I have cleared my plaque psoriasis on my elbows. I didn’t have flaky skin, it wasn’t sore, it wasn’t red. When I have a flare up, I apply it[]” (emphasis added by FDA).
[4] Statements included the following: (1) “[C]reams I was prescribed were thick, and greasy, and they had an odor and they did not work for me[,] (2) “When I first started … I noticed how light and non-greasy it was [and] [w]ithin days, I started to see results[,]” (3) “I’ve been using DUOBRII for 2 years, it works into my routine […] I have cleared my plaque psoriasis on my elbows […] I didn’t have flaky skin, it wasn’t sore, it wasn’t red[]” (emphasis added by FDA).
[5] FDA underscored that the Clinical Studies section of the PI had no data comparing DUOBRII to other plaque psoriasis drugs on the market and further highlighted that the pivotal trial for DUOBRII excluded patients who had failed to respond on other prescription medications.