The FDA’s Office of Prescription Drug Promotion (OPDP) sent a March 31 Untitled Letter to Bausch Health Companies Inc. over a direct-to-consumer (DTC) video and efficacy webpage for Duobrii (halobetasol propionate and tazarotene) lotion.

“The video and webpage make false or misleading claims and/or representations regarding the risks associated with and the efficacy of Duobrii,” the Untitled Letter alleged. “These violations are concerning from a public health perspective because the video fails to include information regarding serious risks associated with Duobrii, a topical product that bears warnings and precautions related to serious systemic risks and serious skin reactions. In addition, the video and webpage create a misleading impression regarding the overall benefit a patient may expect as a result of Duobrii treatment.”

The webpage and video, which was featured on Lifetime TV’s “The Balancing Act,” had been submitted to OPDP for review.

Duobrii is indicated for the topical treatment of plaque psoriasis in adults and “associated with a number of serious risks.” The product is contraindicated in pregnancy and has warnings and precautions regarding embryofetal risk, hypothalamic-pituitary-adrenal (HPA) axis suppression and other unwanted systemic glucocorticoid effects, local adverse reactions, photosensitivity and the risk for sunburn, ophthalmic adverse reactions, and concomitant skin infections.

The Untitled Letter noted that OPDP expressed similar concerns for Duobrii in February 2020. “Bausch appears to be promoting Duobrii without presenting the serious risks and efficacy of the drug in a truthful and non-misleading manner, despite concerns previously expressed by OPDP,” the letter said.

“The video is misleading because it includes efficacy claims for Duobrii but fails to include important risk information associated with the drug,” the letter said. “Specifically, the video fails to include material facts regarding the warning and precaution for embryofetal risk.”

“This omission is especially concerning given that the patient, who appears to be of child-bearing age and is seen in the video with two young children, states: ‘I’ve been using Duobrii for two 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.’”

“This claim suggests that a female of reproductive potential can initiate Duobrii or use it whenever she has a psoriasis flare up without regard to the measures needed to mitigate the risk of birth defects associated with Duobrii,” the letter said.

The FDA acknowledged that some information regarding embryofetal risk was presented in the video; but “this does not mitigate the misleading impression created by the omission of material facts regarding the need for pregnancy testing and birth control from the video. Moreover, the video fails to include any information regarding the warning and precaution for photosensitivity and the risk for sunburn. This omission is further exacerbated by claims and presentations of a Duobrii-treated patient depicted outside, with exposed shoulders and arms, after discussing the success of her treatment with Duobrii,” the letter said.

In addition, OPDP noted that in earlier scenes in the video, before Duobrii was introduced, the same patient states: “Co-workers, my husband, my kids, even my students would notice my elbow. So, I would wear a lot of three-quarter length sleeves even when it was warm outside . . . .”

“These claims and presentations misleadingly suggest that a patient does not need to take measures to avoid exposure to sunlight after treatment with Duobrii when this is not the case,” OPDP said.

“By omitting serious risks associated with Duobrii and material facts pertaining to serious risks, the video misleadingly suggests that Duobrii is safer than has been demonstrated,” the letter said, adding “the video is also misleading because it fails to present information relating to the warnings and precautions for Duobrii with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of Duobrii.”

As an example, the Untitled Letter noted “important risk information regarding HPA-axis suppression and other unwanted systemic glucocorticoid effects is presented in text-only format in small font relegated to the bottom of the screen. At the same time, benefit claims for Duobrii are prominently presented on the screen in large print while also simultaneously announced verbally by the narrator in the audio portion of the video. The overall effect of disclosing risk information in this manner undermines the communication of important risk information. As a result, the video misleadingly minimizes the risks associated with the use of Duobrii,” OPDP concluded.

Regarding efficacy, the Untitled Letter noted that in the video, the physician spokesperson made this efficacy claim for Duobrii: “Adults with plaque psoriasis now have another topical treatment option. Approved by the FDA in 2019, Duobrii is the first and only topical that combines two active ingredients, both with anti-inflammatory benefits that limit plaque growth.”

“This claim suggests that Duobrii is the first and only topical combination medication indicated for the treatment of plaque psoriasis that combines two active ingredients, both with anti-inflammatory benefits that limit plaque growth (i.e., FDA-approved for the treatment of plaque psoriasis), when this is not the case. There are other FDA-approved topical combination products (e.g., betamethasone and calcipotriene) marketed prior to Duobrii for the treatment of plaque psoriasis,” the letter said.

In addition, the patient spokesperson in the video claimed:

• “I have seen many doctors over the last 11 years for my psoriasis. The creams I was prescribed were thick, and greasy, and they had an odor and they did not work for me.”
• “When I first started using Duobrii, I noticed how light and non-greasy it was. Within days, I started to see results.”
• “I’ve been using Duobrii for two 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.”

“Together, these claims are misleading because they suggest that Duobrii is clinically superior to or more effective than other treatments for plaque psoriasis when this has not been demonstrated,” the Untitled Letter said. “In addition, these claims misleadingly imply that Duobrii has been shown to be effective in patients who failed to respond to other plaque psoriasis treatments, when this is not the case.”

“While these claims may be an accurate reflection of the spokesperson’s own experience with Duobrii, the personal experience of this patient does not support the suggestion that Duobrii is superior to other plaque psoriasis drugs on the market,” the letter said, noting that the Clinical Studies section of the Package Insert said that the pivotal trials of Duobrii evaluated Duobrii versus vehicle lotion, not versus any other treatments for plaque psoriasis. “Moreover, the pivotal trials of Duobrii excluded patients with psoriasis that failed to respond to prescription medication, even partially or temporarily, as determined by the investigator,” the Untitled Letter said.

“Therefore, the available data do not support the suggestions that Duobrii is superior to or more effective than other plaque psoriasis treatments on the market and that Duobrii has been shown to be effective in patients who have failed other plaque psoriasis treatments,” OPDP concluded. “FDA is not aware of evidence to support these claims. If you have data to support these claims, please submit them to FDA for review.”

OPDP acknowledged that the video included the SUPER: “People with psoriasis may respond to treatments differently and at different times. Individual results may vary.” “However, this does not mitigate the misleading impression,” the letter said.

OPDP also contended the webpage made several efficacy claims and presentations, including:

• “Demonstrated synergy: superior efficacy versus the aggregated results of two monotherapies.”
• A graph entitled, “Treatment success at eight weeks with the effect of the vehicle removed.
• A bar graph that depicts “treatment success” as 42.8 percent for Duobrii Lotion and 32.5 percent for the monotherapies aggregated, after the vehicle results are removed.
• “More patients experienced treatment success with Duobrii Lotion than the aggregated success rates of both monotherapies.”
• “Duobrii Lotion exceeded the clinical definition of synergy by 31.7 percent at eight weeks.”

“The webpage creates a misleading impression regarding the efficacy and mechanism of action of Duobrii because it draws conclusions based on data that are inadequate to support such conclusions,” the Untitled Letter said, noting “the claims of ‘demonstrated synergy’ and ‘superior efficacy’ versus the aggregated results of two monotherapies on the webpage 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.”

OPDP acknowledged that the statement: “Post hoc analysis of a Phase 2 clinical trial” is included on the webpage. “However, this does not mitigate the misleading impression created by these claims and presentations because the Phase 2 trial was not designed to support conclusions comparing the efficacy of Duobrii to its aggregated components, minus the vehicle effect.” “Because this analysis was conducted post hoc, there was no prespecified statistical procedure controlling for type 1 error rate (false positive rate) in this Phase 2 trial, so it is not possible to ascertain whether the findings were attributable to treatment with Duobrii and its components, or merely due to chance. As a result, these findings are exploratory (hypothesis-generating),” the Untitled Letter said.

“Therefore, claims and presentations that draw conclusions (e.g., ‘demonstrated synergy’ and/or ‘superior efficacy’) are misleading,” OPDP concluded. “Furthermore, this presentation of data regarding the Phase 2 trial is misleading because it overstates the efficacy of the drug by inaccurately describing treatment success at eight weeks. Specifically, the claims and presentation imply that the difference in efficacy between Duobrii and the aggregate of tazarotene and halobetasol (its individual components) was 10.3 percent, when the absolute difference between Duobrii and the aggregate of its individual components was only 0.6 percent in the actual topical lotion dosage form used in the Phase 2 trial (52.5 percent versus 51.9 percent). In the trial, Duobrii and its components were administered topically in the same vehicle lotion, which provided a 9.7 percent response rate. However, the webpage presents results that were analyzed post hoc after the 9.7 percent vehicle lotion response rate was removed from Duobrii and each of its individual components.”

“This webpage, therefore, presents a much larger difference in efficacy between treatment arms than was actually demonstrated. As a result, this presentation is misleading,” the Untitled Letter concluded.

In addition, the U.S. Department of Justice is allegedly investigating Bausch over the company’s marketing of four drugs, including Duobrii, according to media reports. The other drugs are Bryhali and Siliq, which are also used to treat plaque psoriasis, as well as Jublia, a fungal treatment.

According to the reports, the DOJ sent Bausch a civil investigative demand late last year about the company’s promotion of the drugs for unapproved uses.

This is the second Untitled Letter OPDP has issued this year and the third enforcement letter.

Editor’s note: All FDA Warning and Untitled Letters are available in Thompson Information Services’ FDA Enforcement Letter Database, which is available to subscribers of Thompson's FDA Compliance Expert.