- 39.2% (299/763) of subjects included in the interim analysis achieved complete disease clearance (PGA score of 0)
- In an integrated analysis 63.5% of subjects achieved PASI75 and 44.2% of subjects achieved PASI90
- Improvement in treatment effect beyond 12 weeks observed in the integrated analysis
- Remittive benefit of approximately four months observed following treatment discontinuation
- No new safety signals were observed over 52 weeks; consistent safety and tolerability observed for all locations and durations of treatment
- Data will be included in NDA submission for tapinarof, expected mid-2021
LONG BEACH, Calif., and BASEL, Switzerland, February 18, 2021 — Dermavant Sciences, a clinical-stage biopharmaceutical company dedicated to developing and commercializing innovative therapeutics in immuno-dermatology, today announced positive safety and efficacy results from a planned interim analysis of PSOARING 3, its long-term, open-label safety study that, along with previously reported PSOARING 1 and PSOARING 2 pivotal efficacy trials, comprise Dermavant’s Phase 3 program for tapinarof in adult patients with plaque psoriasis.
Tapinarof is a novel, once-daily therapeutic aryl hydrocarbon receptor modulating agent (TAMA), cosmetically elegant, steroid-free topical cream, being developed for the treatment of plaque psoriasis and atopic dermatitis.
While the PSOARING 3 long-term safety study remains ongoing, a preplanned interim analysis was conducted once at least 100 subjects had received tapinarof cream, 1% for 52 weeks, and a further 300 subjects had received tapinarof cream, 1% for 26 weeks.
Data from this interim analysis will be included in the company’s prospective New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA). Dermavant expects completion of the PSOARING 3 long-term safety study in 1H 2021, with an NDA submission in mid-2021.
- In the PSOARING 3 interim analysis:
- 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, which indicates 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 observed, suggesting treatment durability over time.
- Integrated Analysis: In addition to the PSOARING 3 study results, an integrated analysis of efficacy was performed that included data from PSOARING 1, PSOARING 2 and the PSOARING 3 interim analysis:
- 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.”
- Tapinarof cream, 1% was reported to be well-tolerated by both subjects and investigators. The discontinuation rate due to adverse events (AEs) at the time of the interim analysis was 5.8%, generally consistent with the PSOARING 1 (5.6%) and PSOARING 2 (5.8%) pivotal trials. No new safety signals were observed.
- No increased risk of AEs was observed with longer use of tapinarof cream, 1%. The AE profile of tapinarof cream, 1% 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 the 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.
- As in the previous PSOARING 1 and PSOARING 2 trials, no treatment-related serious adverse events (SAEs) were reported.
Remittive Effect (Maintenance of Clear/Almost Clear While Off-Therapy)
In the PSOARING 3 interim analysis, for subjects entering PSOARING 3 with a PGA score of 0 (n=78), the median time to disease worsening (defined as a PGA score of ≥2) following treatment discontinuation was approximately 115 days.
“Having deep clinical experience with tapinarof across five studies, its potential remittive effect has always been very intriguing to me, and is a unique aspect of this new chemical entity,” said Robert Bissonnette, MD, FRCPC, Chief Executive Officer and Medical Director at Innovaderm Research. “This interim analysis indicates the potential remittive effects of tapinarof which, if approved, could facilitate disease management for long-suffering psoriasis patients.”
“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,” Dr. 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.”
“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, Chief Executive Officer 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.”
The data from this interim analysis will be submitted for presentation at upcoming medical congresses and to a peer-reviewed medical journal for publication.
About Dermavant’s Phase 3 Program for Tapinarof in Psoriasis
Dermavant’s pivotal Phase 3 clinical program for tapinarof in adult plaque psoriasis consists of PSOARING 1 (NCT03956355) and PSOARING 2 (NCT03983980), as well as PSOARING 3 (NCT04053387), the ongoing long-term safety study.
PSOARING 1 and PSOARING 2, which collectively enrolled 1,025 patients, were two identically designed, multi-center, randomized, vehicle-controlled, double-blind, parallel group studies conducted in North America that evaluated the safety and efficacy of tapinarof cream, 1% dosed once daily (QD) for 12 weeks versus vehicle QD in adult patients aged 18-75 years diagnosed with plaque psoriasis. The primary endpoint of both studies was a PGA score of clear (0) or almost clear (1) with a minimum 2-grade improvement from baseline at Week 12.
PSOARING 3 is a long-term, open-label, extension study to evaluate the safety and efficacy of tapinarof cream, 1% for the treatment of plaque psoriasis in adults. Subjects in the study had previously completed treatment with tapinarof or vehicle in either the PSOARING 1 or PSOARING 2 Phase 3 pivotal efficacy and safety studies. PSOARING 3 consists of up to 40 weeks of tapinarof cream, 1%, and a 4-week safety follow-up period. As such, subjects who received drug during PSOARING 1 and PSOARING 2 completed PSOARING 3, having received treatment with tapinarof cream for up to 52 weeks. Greater than 90% of eligible patients who completed PSOARING 1 and PSOARING 2 enrolled in PSOARING 3.
Psoriasis is a chronic, systemic, inflammatory skin disease characterized by red patches and plaques with silvery scales on the skin. Psoriasis affects approximately 8 million people in the United States and 125 million worldwide.
Psoriasis can begin at any age, but typically has two peaks of onset, the first at age 20 to 30 years and the second at age 50 to 60 years. People with psoriasis are at an increased risk of developing other chronic and serious health conditions. Comorbidities include psoriatic arthritis, inflammatory bowel disease, hypertension, diabetes, obesity, and depression. Psoriasis has a significant impact on quality of life and on psychological health.
Dermavant Sciences, a subsidiary of Roivant Sciences, is a clinical-stage biopharmaceutical company dedicated to developing and commercializing innovative therapeutics in immuno-dermatology. Dermavant’s focus is to develop therapies that have the potential to address high unmet medical needs while driving greater efficiency in research and clinical development. The company’s robust medical dermatology pipeline includes both late-stage and earlier-stage-development product candidates the company believes could address important immuno-dermatological conditions, including psoriasis, atopic dermatitis, vitiligo, primary focal hyperhidrosis, and acne. Dermavant is developing its lead product candidate, tapinarof (DMVT-505), as a novel therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream for the treatment of plaque psoriasis and atopic dermatitis, which affect approximately 8 million and 26 million people in the United States, respectively. The company reported positive Phase 3 results for tapinarof cream in adult patients with plaque psoriasis. For more information, please visit www.dermavant.com, and follow us on Twitter (@dermavant) and LinkedIn (Dermavant Sciences).
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