Tapinarof shows ‘robust efficacy’ in phase 3 trials
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Once-daily topical tapinarof cream reduced the severity of plaque psoriasis, as well as improved patient-reported outcomes, according to two phase 3 clinical trials.
A novel, aryl hydrocarbon receptor-modulating agent, tapinarof (Dermavant) modulates the expression of interleukin-17 and is a brand-new mechanism of action in development for the treatment of psoriasis.
“Tapinarof is a whole novel class of molecule that works by a mechanism we haven’t used before, but the important thing is it’s not a steroid,” Mark G. Lebwohl, MD, dean for clinical therapeutics and chair emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai and the study’s lead author, told Healio. “When we treat psoriasis the most commonly prescribed drugs are steroids, and they have a number of side effects.”
A nonsteroid treatment option could avoid those side effects, specifically atrophy of the skin, which is a common problem in areas such as the groin, armpits and face, he added.
The identical PSOARING-1 and PSOARING-2 trials studied once-daily tapinarof cream 1% compared with vehicle.
Patients with all levels of disease were included in the trials, which enrolled 510 and 515 patients, respectively.
Primary efficacy was defined as Physician Global Assessment (PGA) score of 0 or 1 (clear or almost clear) and a decrease of at least 2 points of the 5-point PGA scale at 12 weeks. Secondary endpoints included a decrease of at least 75% in the Psoriasis Area and Severity Index (PASI 75), a decrease in PASI of at least 90% (PASI 90) and a mean change in percentage of total body surface area (BSA) affected.
Patient reported outcomes included a decrease in Peak Pruritus Numeric Rating Scale (PP-NRS), a change in the Dermatology Life Quality Index (DLQI) and a mean change in Psoriasis Symptom Diary scores.
“This is the first time we’ve illustrated or shared the totality of the data associated with the PSOARING programs and we are very excited about these results, the consistency of the details and the outcomes across the spectrum of everything we are evaluating,” Philip M. Brown, MD, JD, chief medical officer of Dermavant, told Healio.
In PSOARING 1, a PGA response was recorded in 35.4% of those in the tapinarof treatment group, compared with 6% of those in the vehicle group, while 40.2% of the PSOARING 2 treatment group and 6.3% of the PSOARING 2 vehicle group had the same response at week 12.
A PASI 75 response was evident in 36.1% and 47.6% of the treatment groups, compared with 10.2% and 6.9% of the vehicle groups. PASI 90 response was observed in 18.8% and 20.9% in the two treatment groups, compared with 1.6% and 2.5% in the respective vehicle groups.
“These are endpoints that are typically associated with systemic products,” Brown said. “This illustrates the effects of tapinarof in the ability to reduce disease burden in a really meaningful way.”
Additionally, BSA involvement had a mean decrease of –3.5 percentage points at 12 weeks in the first trial’s tapinarof group, compared with –0.2 in its vehicle group. Trial 2’s BSA reduction was similar with a mean decrease of –4.2 percentage points in the tapinarof group and 0.1 percentage points in the vehicle group.
Itch, as measured by the patient-reported PP-NRS score, was reduced by a mean of –3.6 and –3 in the treatment groups, as compared with –2.7 and –1.4 in the vehicle groups.
A decrease of at least 4 PP-NRS points was reported by 60.7% and 56.9% of those in the treatment groups who had a baseline score of at least 4 points. This compared with 43.2% and 29.6% of those in the vehicle groups.
DLQI scores had a mean change of –4.6 in trial 1’s tapinarof group and –2.8 in its vehicle group, and –4.4 in trial 2’s treatment group and –1.1 in its vehicle group.
“Tapinarof behaves in a very predictable and consistent fashion,” Brown said. “The results observed are incredibly consistent between each of these two studies. The addition of the patient-reported data has illustrated the impact that can be achieved from a subjective standpoint.”
Adverse events were reported in 50.3% and 54.5% of the treatment groups, compared with 22.4% and 26.2% of the vehicle groups, with no adverse events being considered serious.
Folliculitis was the most common adverse event in the trials, with 23.5% and 17.8% in the treatment groups and 1.2% and 0.6% in the vehicle groups.
Other adverse events included contact dermatitis (5% and 5.8% of treatment groups and 0.6% and 0% of vehicle groups) and headaches (3.8% of both treatment groups and 2.4% and 0.6% of the vehicle groups).
“Tapinarof is effective, its remission is durable, and the side effects are limited,” Lebwohl said.
“AHR modulation, which is illustrated by tapinarof, has shown extremely robust efficacy,” Brown added. “This new mechanism of action, being a nonsteroidal, will offer an additional choice in the armamentarium of products clinicians are going to have available to them.”