Topical brepocitinib efficacious in treatment of atopic dermatitis

Previously administered orally, brepocitinib proved to be effective and well tolerated as a topical formation in patients with mild to moderate atopic dermatitis, according to a phase 2b study.

“We hypothesize that topical administration of brepocitinib, given its small molecular weight and amenability to topical formulation, could reduce systemic exposure and provide robust efficacy to participants with mild to moderate AD,” Megan N. Landis, MD, dermatologist and associate professor of dermatology at the University of Louisville School of Medicine in Louisville, Kentucky, and colleagues wrote.

In this phase 2b, double-blind, dose-ranging, 6-week study, researchers evaluated the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2/Janus kinase 1 inhibitor, in patients with mild to moderate AD.

A total of 292 participants (mean age, 40.2 years; 53.4% women) were enrolled and randomly assigned to receive brepocitinib 0.1% or 3% once daily; brepocitinib 0.3% or 1% once or twice daily; or vehicle once or twice daily. Eligible participants had a clinical diagnosis of AD for at least 3 months, an IGA score of 2 to 3, a body surface area involvement of 2% to 20% and an EASI total score of 3 to 21.

Both brepocitinib 1% once daily and twice daily groups achieved the primary endpoint of showing statistically significant greater least squares (LS) mean percentage reductions in EASI from baseline at week 6 (least squares [LS] mean, –70.1; 90% CI, –82.1 to –58 and LS mean, –75; 90% CI, –83.8 to –66.2, respectively) compared with respective vehicle groups (LS mean, –44.4; 90% CI, –57.3 to –31.6 and LS mean, –47.6; 90% CI, –57.5 to –37.7).

Additionally, a significantly greater proportion of five of the six active treatment groups achieved IGA scores of clear or almost clear as well as a 2-point reduction in IGA score from baseline compared with vehicle. The exception was the brepocitinib 1% twice daily group, which was numerically greater compared to twice-daily vehicle but did not reach statistical significance.

Affected body surface area percentages decreased in all active treatment groups by week 6, with 0.3% once daily (LS mean, –54.2), 3% once daily (LS mean, –51.4), 1% once daily (LS mean, –60.6) and 1% twice daily (LS mean, –63) achieving statistically greater decreases from baseline.

According to the researchers, there were no serious adverse events or deaths.

“The results of this study showed that topical brepocitinib is effective and well tolerated in participants with mild to moderate AD,” Landis and colleagues wrote. “Further studies are required to evaluate brepocitinib using a larger sample size and a longer treatment period.”