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A phase 1b study on the toll-like receptor (TLR)7/8 inhibitor afimetoran in cutaneous lupus erythematosus (CLE) participants demonstrated favorable safety, tolerability, and exploratory efficacy.
A phase 1b, randomized, double-blind, placebo-controlled study has provided the first evidence of the clinical benefit of afimetoran in participants with cutaneous lupus erythematosus (CLE). This drug is an orally available, potent, and selective toll-like receptor (TLR)7/8 inhibitor. The safety and efficacy results support further clinical investigation of afimetoran in lupus.
A distinct unmet need exists for CLE therapies; it has been more than 50 years since the last therapy was approved. Afimetoran is a first-in-class inhibitor of TLR7/8. A phase 1b study (NCT04493541) investigated the safety, tolerability, and exploratory efficacy of afimetoran in participants with CLE.1 The results were presented by Fareeda Hosein, MD, MBA (Bristol Myers Squibb).
The study included 13 participants who were aged 18–65, diagnosed with either SLE or had biopsy-proven CLE, had a modified CLE Disease Area and Severity Index-Activity (CLASI-A) score of at least 6, and were antinuclear antibody positive. They could use oral corticosteroids and/or antimalarials at baseline. The participants were randomized 2:1 to once-daily oral afimetoran 30 mg (n=8) or placebo (n=5) for 16 weeks. The primary endpoints were safety and tolerability, while efficacy was exploratory.
Afimetoran demonstrated a favorable safety profile and was well tolerated. There were no serious adverse events (AEs) or safety signals in any participant. In the experimental arm, 1 participant discontinued treatment due to a symptomatic COVID-19 infection. The number of participants with AEs was 5 (63%) in the afimetoran group and 4 (80%) in the control group. These AEs were mild or moderate and resolved without intervention. Plasma concentrations exceeded the projected targeted inhibition concentration over 24 hours, supporting the 30 mg once-daily dosing.
The exploratory efficacy response was in line with the pharmacodynamic effects. Participants in the treatment group showed a greater reduction in CLASI-A scores as early as week 4 compared with placebo. By week 16, the rate of participants achieving the minimum clinically important difference in CLASI-A scores (>4 points from baseline) was higher for afimetoran (50%) than placebo (0%).
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