Encouraging results of afimetoran in participants with cutaneous lupus

A phase 1b, randomised, 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 over 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 Dr Fareeda Hosein (Bristol Myers Squibb, NJ, USA).

Participants 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 ≥6, and were antinuclear antibody positive. They could use oral corticosteroids and/or antimalarials at baseline. The 13 participants were randomised 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 favourable 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%).

1. Hosein A, et al. Safety, tolerability, and exploratory efficacy of afimetoran, a TLR7/8 inhibitor, in patients with cutaneous lupus erythematosus: A phase 1B randomized, double-blind, placebo-controlled study. L17, ACR Convergence 2023, 10–15 November, San Diego, USA.

Medical writing support was provided by Michiel Tent.
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Posted on 1 December 20231 December 2023