Deuterated colexitinib is effective in patients with cutaneous lupus, including concurrent SLE

New findings suggest that treatment with deucravacitinib may be a promising treatment option for patients with cutaneous lupus, including those who also have subacute cutaneous lupus erythematosus (SCLE).

Results have been released from the PAISLEY CLE trial, a global Phase 2 randomized, double-blind, placebo-controlled trial evaluating deucravacitinib, a first-in-class oral tyrosine kinase 2 (TYK2) selective allosteric inhibitor. The study looked specifically at patients with active discoid lupus erythematosus (DLE) and/or small cell lung cancer (SCLE), with or without systemic lupus erythematosus (SLE).

Deuterated colexitinib has been approved by regulatory agencies in multiple countries for the treatment of moderate to severe psoriasis, and during the PAISLEY analysis period, the drug showed efficacy on multiple clinical endpoints in patients with SLE. In the current study, the team sought to establish these results by specifically targeting cutaneous lupus manifestations, including those with and without systemic involvement, limiting SLE cases to 50% of the trial population. Eligible adult subjects will have a histologically confirmed diagnosis of moderate to severe DLE or SCLE. These conditions were defined as a baseline Cutaneous Lupus Disease Area and Severity Index Activity (CLASI-a) score of 8 or higher.

The primary endpoint focused onThe mean percentage change from baseline in CLASI-A score at 16 weeks. In terms of secondary and exploratory endpoints, examples include a 50% or greater improvement in CLASI-a (CLASI-50), a 70% or greater improvement in CLASI-70, the trajectory of CLASI-a score improvement over time, and patient-reported skin pain levels via a visual analog scale. Of note, this phase 2 study used a two-sided alpha level of 0.10 to determine statistical significance without adjustment for several different comparisons.

Overall, the study met its primary endpoint, with patients receiving deuterated colexitinib significantly improving their CLASI-A scores compared to placebo. Specifically, the mean percentage reduction in CLASI-A scores was -47.5% and -50% for the 3 mg and 6 mg doses, respectively, compared to -28.4% for the placebo cohort. The P values u200bu200bfor these differences were 0.0670 and 0.0385, respectively, indicating statistical significance at a predetermined threshold. Likewise, absolute changes in CLASI-A scores also favored the deuterocolexitinib group, with investigators observing greater baseline decreases compared with placebo.

Byby 16 weeks, more than half of those taking either dose achieved CLASI-50, compared with just 19% of those in the placebo group. The drug also had higher CLASI-70 response rates, especially for the 3 mg dose, which reached statistical significance. Studies also noted improvements in skin pain, although these improvements were described using numbers rather than statistics.

Notably, the treatment benefit emerged as early as 4 weeks and persisted throughout the 52-week analysis. Deuterated colexitinib was shown to be well tolerated. No new safety concerns were identified, and adverse events (AEs) were mostly mild to moderate in severity. Among the most reported events, examples include headache, upper respiratory tract infection, and dermatitis acneiformis. Investigators also stressed that there were no interruptions due to adverse events.

There were no reports of serious complications such as herpes zoster, venous thromboembolism, cardiovascular events, malignancy, or opportunistic infections. Laboratory parameters also remained stable, with no clinically significant abnormalities seen in any treatment group in the analysis.

In summary, deuterated colexitinib offers a promising drug option for patients with cutaneous lupus, including those who also have SLE. Its favorable safety profile and significant clinical improvements support ongoing development, including continued evaluation of the drug in the POETYK SLE Phase 3 trial.

Reference materials:https://go.drugbank.com/drugs/DB16650