• Danka Svecova, Martin W Lubell, Florence Casset-Semanaz, Harald Mackenzie, Roland Grenningloh, and James G Krueger.
• Faculty of Medicine of Comenius University, Bratislava, Slovakia.
• J. Am. Acad. Dermatol. 2019 Jul 1; 81 (1): 196-203.

BackgroundInterleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease.ObjectivesTo evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis.MethodsThis multicenter, double-blind, placebo-controlled dose escalation phase 1 study randomized 44 patients 4:1 to treatment with subcutaneous M1095 (30, 60, 120, or 240 mg) or placebo biweekly for 6 weeks, in 4 ascending dose cohorts.ResultsThe most frequent treatment-emergent adverse events with M1095 were pruritus (n = 4) and headache (n = 3); 2 patients withdrew owing to adverse events (injection site reaction and elevated liver enzyme levels). The terminal half-life of M1095 was 11 to 12 days. The area under the curve/maximum concentration was dose proportional. Of 10 M1095-treated patients positive for antidrug antibodies, 5 showed treatment-emergent antidrug antibody responses. There was no effect on M1095 exposure. Marked decreases in psoriasis inflammatory markers were observed with M1095. By day 85, 100% and 56% of patients receiving M1095, 240 mg, achieved psoriasis area and severity index 90 and 100, respectively. Improvements in static Physician's Global Assessment and affected body surface area were also seen.LimitationsInterpretation of efficacy data is limited by the small sample size.ConclusionMultiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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