麻豆传媒

Last year, the FDA (benvitimod, VTAMA), a non-steroidal, first-in-class drug for the treatment of plaque psoriasis.

The drug also is in phase 3 trials for atopic dermatitis (AD). Investigators are optimistic about its efficacy for this, and perhaps other, conditions.

That's according to a review, published in the , led by researchers from Innovaderm Research Inc., a Montreal, Canada firm that has participated in 10 tapinarof-related trials since 2007, encompassing roughly 250 patients who were treated with the drug.

The following review excerpts have been edited for length and clarity.

What was the impetus for the review?

In 2022, the FDA approved a cream formulation of tapinarof 1% for once-daily treatment of psoriasis vulgaris.

Initially known as WBI-1001, tapinarof is an aryl-hydrocarbon receptor agonist that entered clinical trials at Innovaderm Research in August 2007.

In their article, Innovaderm researchers examine the development of tapinarof for the treatment of psoriasis and AD and discuss practical considerations based on 15 years of experience with the drug.

Tapinarof for Psoriasis: Key Data Points

A single-center, phase 2 study with 61 patients randomized (2:1) to tapinarof or control showed that tapinarof had a fast onset of action and was superior to control for the treatment of psoriasis.

At week 12, 67.5% of patients achieved a physician global assessment (PGA) of clear or almost clear, compared with 4.8% for the control group.

These results were confirmed by a phase 2b dose ranging multi-center study, in which reformulated tapinarof at 0.5% and 1% was studied once or twice a day compared to control. The study's primary endpoint, PGA 0/1 and a two-point decrease in PGA, was achieved by 65% and 56% of patients with the 1% concentration applied twice or once daily, respectively, compared with 11% and 5% for twice- and once-daily placebo, respectively.

Improvements also were maintained over 4 weeks of follow-up, despite treatment discontinuation, leading investigators to become keenly interested in tapinarof's long-term treatment potential.

Tapinarof for AD: Current Data and Research Status

In an early study, 34 people with AD were randomized (1:1:1) to tapinarof 0.5%, 1%, or control for 4 weeks. At week 5, 50% of patients in both treatment groups achieved a status of clear or almost clear as compared to 8.3% for the control arm. Improvement was maintained 1 week after treatment cessation in the 1% group.

This study was followed by a multicenter, 148-patient, phase 2 study, which confirmed these findings for eczema, leading to a larger study program using the tapinarof formulation that is already FDA-approved for psoriasis.

Tapinarof is currently undergoing a in adults and children as young as 2 years. The drug reached all primary and secondary endpoints in the trial, with tapinarof's manufacturers seemingly hopeful for FDA approval for this indication, though a timeline for such an action appears uncertain.

What is the safety profile for tapinarof?

Tapinarof is typically well tolerated but can induce a follicular inflammatory reaction and dermatitis in some patients.

In fact, local skin reactions were observed in all studies with tapinarof. Two types of local skin reactions have been systematically reported: folliculitis/follicular papules and dermatitis.

Folliculitis has been used to describe a papulo-pustular reaction seen in approximately 20% of patients with psoriasis treated with tapinarof. However, review authors asserted that this percentage is inflated, the result of a mischaracterization brought on by overly broad coding definitions. As an illustration, in one study conducted in psoriasis, folliculitis was reported in 10% of cases, with application site papules reported in 7.5% of patients.

Headaches have also been reported more frequently in patients treated with tapinarof. In the two phase 3 psoriasis trials, headaches were reported per trial in 3.8% of patients randomized to tapinarof compared to 2.4% and 0.6% in control patients.

What are the clinical implications, both in the present and future, for tapinarof and dermatologists who manage people with inflammatory skin diseases?

The FDA's approval of tapinarof for the treatment of psoriasis in adults adds a new, novel agent to the therapeutic armamentarium. Approval for the treatment of moderate-to-severe eczema in adults and children may not be far behind.

In the meantime, further studies are needed in patients with extensive psoriasis to determine if long-term remission, induced by tapinarof, can be maintained with periods of intermittent use, researchers wrote. If successful, this approach may reduce the need for lifelong systemic treatment.

Further, there are no data comparing tapinarof to existing systemic or topical therapies, or evaluating its effectiveness and safety when used in combination with other therapies.

Implications for practice

• Approved by the FDA last year, tapinarof (VTAMA) is a novel, effective, easy-to-use agent for treating plaque psoriasis in adults.
• Current trials in adults and children with eczema have delivered similarly promising results, with drugmakers hopeful for FDA approval for this indication.
• Evidence of long-term efficacy could ultimately reduce need for lifelong treatments.