Once-daily tapinarof 1% cream has shown highly significant treatment success in a substantial proportion of psoriasis patients in the identical, multicentre, phase 3 PSOARING 1 and PSOARING 2 trials.
“In psoriasis, we have a significant need for effective topical therapies that do not restrict the amount of time we can apply them or the locations on the body where we can apply them,” stated Prof. Mark Lebwohl (Icahn School of Medicine at Mount Sinai, USA) . He referred to restrictions of high-potent topical corticosteroids that cannot be used in the face or intertriginous sites, for example.
Tapinarof is a first in class, non-steroidal topical aryl hydrocarbon receptor-modulating agent. “Tapinarof enters the cell where it binds to the aryl hydrocarbon receptor. That complex then enters the nucleus where it joins with the aryl hydrocarbon receptor nuclear translocator and that entire complex regulates gene expression, resulting in a reduction in inflammatory cytokines and an increase in barrier proteins,” Prof. Lebwohl explained the mode of action.
Tapinarof was evaluated in the identical multicentre PSOARING 1 (PSO1) and PSOARING 2 (PSO2) studies. The studies included a total of 1,025 adults with a mean age between 49.1 and 50.0 years, the proportion of males was 50.6% and 62.2%, the mean weight was 89.6 kg and 92.9 kg, and the participants had a Physician Global Assessment (PGA) of 2-4, respectively. Roughly 80% had moderate disease and more or less 10% mild or severe psoriasis, respectively. The mean Psoriasis Area Severity Index (PASI) ranged from 8.7 to 9.3. In both trials, patients were randomised 2:1 to either tapinarof 1% or vehicle once -daily. The primary endpoint was a PGA response of 0 or 1 with ≥2-grade improvement at week 12.
In PSO1 and PSO2, 35.4% and 40.2% in the tapinarof group achieved this PGA goal versus 6.0% and 6.3% in the vehicle group with a P<0.0001 for both comparisons. At week 12, the results for the key secondary endpoint defined as the rate of patients with PASI 75 were similar: 36.1% and 47.6% in the tapinarof group versus 10.2% and 6.9% in the vehicle group with again a P<0.0001 for both differences.
Looking at safety, most of the adverse events (AE) were mild in severity (PSO1: tapinarof 22.4% vs vehicle 9.4%; PSO2: tapinarof 23.3% vs vehicle 9.9%) or moderate (PSO1: tapinarof 24.1% vs vehicle 12.9%; PSO2: tapinarof 28.6% vs vehicle 16.3%) with a low study discontinuation due to AE rate of 5.6% and 5.8% in PSO1 and PSO2. The most common treatment-related AE were folliculitis, contact dermatitis, headache, and pruritus.
“Tapinarof has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians with a novel non-steroidal topical treatment option that is highly effective and well-tolerated,” Prof. Lebwohl concluded.
- Lebwohl M, et al. Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Efficacy and Safety in Two Pivotal Phase 3 Trials. D3T03.3D, EADV Virtual, 29-31 October 2020.
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