Phase 3 Results Support Long-Term Use of Tapinarof Cream

Dermavant announced the results from its planned interim analysis of PSOARING 3 (NCT04053387), reporting positive long-term safety and efficacy of tapinarof cream 1% (GSK2894512, Dermavant) in adult patients with plaque psoriasis, according to a company press release.¹

“We are excited to share the results from our interim analysis of PSOARING 3, which represent yet another milestone for Dermavant as we progress towards a mid-2021 NDA submission for tapinarof in adult patients with psoriasis,” said Todd Zavodnick, CEO of Dermavant. “We are now focused on compiling a comprehensive NDA submission highlighting the treatment effect, durability on-therapy, remittive effect off-therapy, safety, and tolerability of tapinarof. At the same time, we are furthering our commercial readiness in anticipation of tapinarof’s potential approval, and advancing the other assets in our development pipeline.”

Tapinarof is a novel, once-daily, aryl hydrocarbon receptor modulating agent (TAMA), steroid-free topical cream that is currently being developed for the treatment of plaque psoriasis, and atopic dermatitis. PSOARING 3, an on-going, long-term, open-label safety study, is a part of Dermavant’s phase 3 clinical program studying tapinarof in adult plaque psoriasis that also consists of PSOARING 1 (NCT03956355) and PSOARING 2 (NCT03983980).

Despite PSOARING 3 being an ongoing long-term safety study, researchers conducted a preplanned interim analysis once at least 100 subjects had received tapinarof cream,1% for 52 weeks, and an additional 300 subjects had received tapinarof cream 1% for 26 weeks.

Results of the interim analysis demonstrated the following efficacy data:

• 57.3% (298/520) of subjects who entered the study with a Physician Global Assessment (PGA) score ≥ 2 achieved a PGA score of 0 or 1, indicated tapinarof’s increased therapeutic effect beyond the 12-week double-blind treatment periods in PSOARING 1 and 2.
• 39.2% (299/763) of subjects included in the interim analysis achieved complete disease clearance (PGA score = 0).
• No evidence of tachyphylaxis was observed, thus suggesting treatment durability over time.

An integrated analysis of efficacy was also conducted that included data from PSOARING 1, PSOARING 2 and the PSOARING 3 interim analysis. The data consisted of the following:

• A PGA response of 0 (clear) or almost clear (1), plus at least a 2-grade improvement from baseline, at any time point, was observed in 57% (518/915) of subjects.
• PASI75, at any time point, was achieved by 63.5% (581/915) of subjects.
• PASI90, at any time point, was achieved by 44.2% (404/915) of subjects.

“The achievement of a PGA score of 0 or 1 by 57.3% of patients following tapinarof treatment is impressive and will be important to patients and prescribers,” said Bruce Strober, MD, PhD, clinical professor of dermatology at Yale University School of Medicine and lead investigator for the PSOARING 3 study. “With nearly 40% of patients achieving complete disease clearance, tapinarof has the potential to be an important new topical treatment option for patients suffering from psoriasis.”

Additionally, the interim analysis demonstrated the following safety data:

• Both subjects and investigators reported tapinarof cream 1% was well-tolerated. The discontinuation rate due to adverse events (AEs) at the time of the interim analysis was 5.8%, consistent with PSOARING 1 (5.6%) and PSOARING 2 (5.8%). No new safety signals were observed.
• No increased risk of AEs was observed with longer use of tapinarof cream,1%. The AE profile reported in the interim analysis of PSOARING 3 was consistent with the AE profile observed in the previous PSOARING 1 and PSOARING 2 trials, with a majority of AEs localized to site of application, and mild to moderate in nature. The most commonly reported AEs were folliculitis, contact dermatitis, and upper respiratory tract infection.
• No treatment-related serious adverse events (SAEs) were reported.

“This interim analysis from PSOARING 3 provides additional support for tapinarof’s previous safety results, exhibited across multiple trials, adding a 52-week observation period to the previous maximum of 12 observed weeks. Importantly, these results appear to be consistent, and we observed no new safety signals in this interim analysis, and no worsening of the underlying safety profile for tapinarof observed in our PSOARING 1 and PSOARING 2 trials,” said Philip Brown, MD, JD, chief medical officer of Dermavant.

“Turning to efficacy,” Brown continued, “based on the data from our PSOARING 1 and 2 pivotal trials, we believed that further disease improvement was likely from continued use of tapinarof. Our hypothesis was that a potential durable response on-therapy and a remittive response off-therapy could provide patients with disease control. The interim analysis from PSOARING 3 provides evidence for that belief. The data we are sharing today suggest that continued use of tapinarof may result in an increased and durable effect up to 52 weeks. In addition, today’s interim analysis provides support for tapinarof’s ability to achieve a remittive effect – the time from when a patient achieves complete disease clearance (PGA score = 0) and ceases treatment, to when they next experience a psoriatic flare (PGA score ≥ 2). The remittive effect was approximately four months in duration for patients who entered PSOARING 3 with a PGA score of 0. Consequently, we believe these data point to the potential use of tapinarof, if approved, as a novel, topical non-steroidal, to treat patients with mild, moderate, or severe psoriasis without restriction on skin application sites, and with possible increased treatment benefit for up to 52 weeks.”

According to the company, the data from the interim analysis will be included in the New Drug Application (NDA) submission to the FDA for tapinarof cream 1%. Dermavant plans on completing the PSOARING 3 study in the first half of 2021 and expects the NDA to be filed in mid-2021.

Reference:

1. Positive data from psoaring 3 support long-term use of tapinarof cream in adults with plaque psoriasis, with durable (On-therapy) and remittive (Off-therapy) benefits – dermavant. Accessed February 18, 2021. https://www.dermavant.com/positive-data-from-psoaring-3-support-long-term-use-of-tapinarof-cream-in-adults-with-plaque-psoriasis-with-durable-on-therapy-and-remittive-off-therapy-benefits/