Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study

• Published in: Lupus Vol. 29; no. 14; pp. 1902 - 1913
• Main Authors: Tanaka, Yoshiya, Kondo, Kazuoki, Ichibori, Ayako, Yanai, Yoshiari, Susuta, Yutaka, Inoue, Shinsuke, Takeuchi, Tsutomu
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2020; Sage Publications Ltd
• Subjects: Adult; Autoantibodies; Cell number; Double-Blind Method; Female; Humans; Lupus; Lupus Erythematosus, Systemic; Lymphocytes; Male; Middle Aged; Non-Randomized Controlled Trials as Topic; Peripheral blood; Pharmacodynamics; Pharmacokinetics; Propanolamines; Sphingosine 1-phosphate; Sphingosine-1-Phosphate Receptors; Systemic lupus erythematosus; lymphocyte subsets; lymphocyte count; Systemic lupus erythematosus; anti-ds-DNA antibody; S1P modulator; amiselimod
• ISSN: 0961-2033; 1477-0962; 1477-0962
• DOI: 10.1177/0961203320966385

Objective To evaluate the safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy of amiselimod, an oral selective sphingosine 1-phosphate receptor-1 modulator, in patients with systemic lupus erythematosus (SLE). Methods A multicenter, open-label phase Ib trial was conducted in Japan. Patients in Part 1 and Part 2-B received 0.2 mg amiselimod while those in Part 2-A received 0.4 mg amiselimod for 24 weeks. Results Seventeen subjects received 0.2 or 0.4 mg amiselimod. Amiselimod and amiselimod-P plasma concentrations increased dose-dependently. Peripheral blood lymphocyte count decreased in all patients after amiselimod treatment, with no clear dose response. There were no serious/severe adverse events (AEs) or clinically meaningful cardiac effects. Five subjects were withdrawn from amiselimod treatment following a decrease in lymphocyte count to <200/μl. Anti-double stranded-DNA antibody decreased from baseline to Week 24/end of treatment (EOT), with those in 2 subjects (22.2%) decreasing to within the normal range. Total SLE disease activity index 2000 score decreased by ≥4 at EOT in 7 of 17 subjects. Conclusions Amiselimod was generally well tolerated. While no serious AEs or infectious AEs led to discontinuation, low lymphocyte counts of <200/μl were observed as a laboratory abnormality. Our findings suggest the potential efficacy of amiselimod for patients with SLE. Trial registration: ClinicalTrials.gov identifier: NCT02307643.