FDA Accepts New Drug Application for Tapinarof in Plaque Psoriasis

Dermavant Sciences has announced the FDA has accepted the New Drug Application (NDA) for tapinarof for the treatment of plaque psoriasis in adults.¹

Tapinarof (GSK2894512, Dermavant) is a novel once-daily topical therapeutic aryl hydrocarbon receptor modulating agent (TAMA), which inhibits many of the proinflammatory mediators associated with inflammation and has been shown to enhance the skin barrier function. The steroid-free and cosmetically elegant topical is also being studied as a potential treatment for atopic dermatitis.

The FDA has set the Prescription Drug User Fee Act (PDUFA) target action date in Q2 2022.

“With the FDA acceptance of our NDA for filing, Dermavant is one step closer to potentially providing a new option for adults with mild, moderate, and severe plaque psoriasis, who often deal with itch, pain, disfiguring appearance, and significant emotional and physical distress,” said Todd Zavodnick, CEO of Dermavant. “The entire Dermavant team is now working diligently to prepare for the commercial launch of tapinarof, subject to FDA approval, and we look forward to further discussions with the FDA during the review process of this novel product candidate.”

Study Results

The NDA acceptance is supported by positive data from 2 phase 3, identical, multi-center, randomized, vehicle-controlled, double-blind clinical trials (PSOARING 1; NCT03956355 and PSOARING 2; NCT03983980), as well as positive interim data from an ongoing 40-week, open-label safety study (PSOARING 3; NCT04053387).

In PSOARING 1 and PSOARING 2, a total 1,025 combined patients received either tapinarof cream 1% once daily or vehicle once daily over the course of 12 weeks.² Following the 12-week studies, patients were given the option to participate in an ongoing 52-week safety study, PSOARING 3.

Results of the studies show tapinarof met all primary and secondary endpoints, as well as demonstrated a similar safety profile consistent with previous trials.

In PSOARING 1, 35.4% of patients who received tapinarof 1% (n=340) achieved a Physician Global Assessment (PGA) score of 0 or 1 at week 12 compared with 6% who were treated with vehicle (n=170). Also, 36.1% of patients in the tapinarof group reached Psoriasis Area and Severity Index (PASI) score of 75 at week 12 vs 10.2% of those in the vehicle group.

In PSOARING 2, 40.2% of patients who received tapinarof once daily (n=343) achieved a PGA score of 0 or 1 at week 12 vs 6.3% of those treated with vehicle (n=172). Meanwhile, 47.6% of patients treated with tapinarof reached PASI 75 at week 12 compared with 6.9% of those treated with vehicle. The company also reports up to 80% of patients achieved a ≥1-grade improvement in PGA throughout both studies.

“The PSOARING 1 and PSOARING 2 results support our belief that, subject to FDA approval, tapinarof cream could become a highly beneficial treatment option for adult patients living with mild, moderate and severe plaque psoriasis,” said Philip Brown, MD, JD, chief medical officer of Dermavant, in a press release announcing the initial results from the 2 studies. “With minimal systemic drug exposure, these data point to the potential use of tapinarof as a novel topical non-steroidal, capable of being used in sensitive and difficult to treat areas of the body such as face, groin and under arms. As such, we are excited by the efficacy and safety results of tapinarof exhibited across multiple trials.”

Additionally, researchers saw promising interim data from the ongoing PSOARING 3 study.

Results of the interim analysis demonstrated the following efficacy data³:

• 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.

Also, the interim analysis demonstrated the following safety data:

1. 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.
2. 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.
3. No treatment-related serious adverse events (SAEs) were reported.

References:

1. Dermavant announces fda acceptance for filing of new drug application (Nda) for tapinarof cream for the treatment of adults with plaque psoriasis. Published August 10, 2021. Accessed August 10, 2021. https://www.businesswire.com/news/home/20210810005299/en/Dermavant-Announces-FDA-Acceptance-for-Filing-of-New-Drug-Application-NDA-for-Tapinarof-Cream-for-the-Treatment-of-Adults-with-Plaque-Psoriasis
2. Dermavant Reports Positive Phase 3 Results for Tapinarof Cream in Adult Patients with Plaque Psoriasis. (2020, August 26). Accessed June 4, 2021, from https://www.businesswire.com/news/home/20200826005389/en/Dermavant-Reports-Positive-Phase-3-Results-Tapinarof
3. 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 June 4, 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/