Afimetoran Shown to be Safe, Well-Tolerated for Patients with Cutaneous Lupus Erythematosus

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This new late-breaking data presented at ACR 2023 was the first clinical evidence indicating efficacy of afimetoran for those with CLE.

The drug afimetoran (BMS-986256) is considered to be safe and well-tolerated compared to placebo among individuals with cutaneous lupus erythematosus (CLE), according to late-breaking data presented at the American College of Rheumatology (ACR) 2023 Convergence in San Diego, California.1

This research was presented by Fareeda Hosein, MD, MBA, from Bristol Myers Squibb. Hosein and colleagues noted that this study was important given the lack of new therapies for patients with CLE in more than 50 years.

Additionally, the investigators wrote that current treatments available for those with CLE face several key issues such as off-label use, long-term toxicity, and non-oral administration.

Toll-like receptors (TLRs) that are implicated in systemic lupus erythematosus (SLE) pathobiology, have become known as possible targets for treatments for CLE. The drug afimetoran is an orally bioavailable, selective small molecule inhibitor of TLR7 and TLR8, and it is first-in-class.

Afimetoran was assessed in Hosein and colleagues’ randomized, phase 1b, double-blind, placebo-controlled trial. The study was conducted to look at the drug’s safety, its tolerability, and its exploratory efficacy among those with CLE.

The subjects recruited for this research were in the age range of 18–65 years, had diagnoses of either SLE or biopsy-proven CLE, with SLE based upon the 2019 criteria for classification of EULAR/ACR. Additionally, the study participants were recruited by the investigators if they were antinuclear antibody positive, if they had a modified CLE Disease Area and Severity Index-Activity (CLASI-A) score of ≥ 6, and if there was no evidence of retinal toxicity.

Individuals that had stable baseline doses of oral corticosteroids and/or antimalarials were involved in this research. These subjects underwent randomization in a 2:1 ratio to be treated with either once-per-day oral afimetoran (30 mg) or a placebo over the course of a 16-week study period.

Following the 16 weeks, those involved in the study were subsequently monitored by the research team for a total of 4 weeks following the cessation of their treatment. Overall, the investigators' study focused on evaluating safety and tolerability as primary endpoints, while efficacy was considered as an exploratory endpoint.

There were 8 subjects assigned to the afimetoran treatment arm and 5 to the placebo arm, for a total of 13 subjects that underwent randomization for the study. In the end, 12 of them successfully carried the 16-week treatment through to completion.

The investigators noted that a single participant in the afimetoran arm was found to have discontinued as a result of an adverse event (AE), with a symptomatic infection of COVID-19. The baseline qualities of those involved were shown to be somewhat comparable, but the treatment group

The baseline characteristics of the patients were generally comparable, but the afimetoran arm exhibited higher baseline CLASI-A scores and a greater number of current individuals who smoke versus those in the placebo arm.

The drug showed a strong profile for safety and was found to be well-tolerated compared to placebo, meeting its primary goal. The research team also did not identify any serious AEs or safety signals in vital signs, laboratory tests, or electrocardiography.

They noted that AEs were shown to be mild or moderate and that they resolved themselves by the study’s end. The percent of subjects with reported AEs was found to be lower for those given the drug compared to placebo, at 62.5% vs 80.0%, respectively.

The investigators also reported that those given afimetoran reported greater reductions in CLASI-A scores as early as 4 weeks in (first CLASI-A assessment point). This also was shown to have carried on through to 16 weeks of active treatment and then continued for 4 more weeks following cessation of treatment.

Given these findings, the research team’s data supports further clinical research on this drug for lupus.


  1. F. Hosein, S. Ignatenko, 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. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.