Arcutis Biotherapeutics announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Zoryve (roflumilast) cream, 0.15%, for the treatment of mild to moderate atopic dermatitis (AD) in adult and pediatric patients 6 years of age and older. Zoryve is a once-daily, steroid-free cream designed for rapid disease clearance and significant itch reduction, offering a long-term disease control option.
Clinical Trial Results
The approval is based on positive results from three Phase 3 studies (INTEGUMENT-1, INTEGUMENT-2, and INTEGUMENT-OLE) and a Phase 2 dose-ranging study. The INTEGUMENT-1 and INTEGUMENT-2 trials were double-blind, vehicle-controlled studies evaluating the safety and efficacy of Zoryve cream 0.15% applied once daily for four weeks in 1,337 patients with mild to moderate AD.
Both INTEGUMENT-1 and -2 met their primary endpoint, with a significant percentage of patients achieving IGA Success, defined as a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) score of Clear or Almost Clear plus a 2-grade improvement from baseline at Week 4 (INTEGUMENT-1: 32.0% Zoryve cream vs. 15.2% vehicle, P<0.0001; INTEGUMENT-2: 28.9% Zoryve cream vs. 12.0% vehicle, P<0.0001). Approximately 40% of patients treated with Zoryve cream achieved a vIGA-AD score of Clear (0) or Almost Clear (1) at Week 4 (INTEGUMENT-1: 41.5% vs. 25.2%, P<0.0001; INTEGUMENT-2: 39% vs. 16.9%, P<0.0001), with significant improvement as early as Week 1 (P<0.0001).
Itch Reduction and Long-Term Efficacy
Zoryve cream 0.15% demonstrated rapid and significant improvement in itch within 24 hours of the first application, as measured by the change from baseline in daily Worst Itch-Numeric Rating Scale (WI-NRS) scores (nominal P<0.05). Over 30% of individuals treated with Zoryve cream achieved WI-NRS Success at Week 4 (INTEGUMENT-1: 33.6% vs 20.7% P<0.01; INTEGUMENT-2: 30.2% vs 12.4% P<0.01). WI-NRS Success is defined as at least a 4-point reduction on the WI-NRS 0-10 scale.
More than 40% of patients treated with Zoryve cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at Week 4 compared to vehicle (INTEGUMENT-1: 43.2% vs. 22.0%, P<0.0001; INTEGUMENT-2: 42.0% vs. 19.7%, P<0.0001). Significant improvements based on EASI-75 were observed as early as Week 1 (nominal P=0.0006; nominal P=0.0329).
Safety and Tolerability
Zoryve cream 0.15% was well-tolerated in clinical trials. The incidence of Treatment Emergent Adverse Events (TEAEs) was low, with most TEAEs assessed as mild to moderate in severity. The most common adverse reactions included headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).
Future Availability
Arcutis intends to make Zoryve cream 0.15% widely available through key wholesaler and dermatology pharmacy channels by the end of July. The company is dedicated to ensuring predictable access through the Zoryve Direct Program and the Arcutis Cares patient assistance program.
Frank Watanabe, president and chief executive officer of Arcutis, stated, "With Zoryve, our goal has been to provide a steroid-free topical that can provide effective and fast results, wherever on the body it’s needed, and long-term disease control through a safe and tolerable formulation."
