SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis

Background SDZ ASM 981 is a selective inhibitor of the production of pro-in flammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inf lammatory skin diseases. Objectives This study was: designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the t reatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. Methods This was a double-blind, randomized, parallel-group, multicentre do se-finding study. A total of 260 patients were randomly assigned to treatme nt with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valer ate cream (BMV). Treatment was given twice daily for up to 3 weeks. Results A clear dose-response relationship for SDZ ASM: 981 was evident, wi th 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effe ctive than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of b aseline to end-point: changes in the Eczema Area Severity Index (EASI) and pruritus score, The 1.0% cream was the most effective SDZ ASM 981 concentra tion. BMV was more effective than the SDZ ASM 981 creams tested in this stu dy. It appears that the efficacy plateau was not reached with the SDZ ASM. 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burnin g or a feeling of warmth were the only adverse events reported more frequen tly in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle t reatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent syst emic event reported by 15 of 252 patients) and none was considered to be re lated to treatment. The local tolerability profile of the 1.0% cream was si milar to that of the lower concentrations. Conclusions 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolera ted and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.