Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial

Abstract

Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast Malassezia is regarded as a key pathogenic driver in this disease, but increased Staphylococcus abundances and barrier dysfunction are implicated as well. Here, we evaluated the antimicrobial peptide omiganan as a treatment for SD since it has shown both antifungal and antibacterial activity. A randomized, patient- and evaluator-blinded trial was performed comparing the four-week, twice daily topical administration of omiganan 1.75%, the comparator ketoconazole 2.00%, and placebo in patients with mild-to-moderate facial SD. Safety was monitored, and efficacy was determined by clinical scoring complemented with imaging. Microbial profiling was performed, and barrier integrity was assessed by trans-epidermal water loss and ceramide lipidomics. Omiganan was safe and well tolerated but did not result in a significant clinical improvement of SD, nor did it affect other biomarkers, compared to the placebo. Ketoconazole significantly reduced the disease severity compared to the placebo, with reduced Malassezia abundances, increased microbial diversity, restored skin barrier function, and decreased short-chain ceramide Cer[NSc34]. No significant decreases in Staphylococcus abundances were observed compared to the placebo. Omiganan is well tolerated but not efficacious in the treatment of facial SD. Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action.

Candida albicans and Antifungal Peptides

“…This phase separation of the membrane ultimately leads to membrane permeabilization Facial seborrheic dermatitis in phase II Omiganan was safe and well tolerated but did not result in a significant clinical improvement of seborrheic dermatitis when compared to the use of ketoconazole. (ClinicalTrials.gov Identifier NCT03688971) [ 148 ] PAC113 Targets the mitochondrial complex I, increasing free radicals and inhibiting cellular respiration, with a membrane-lytic activity associated Histatin-derived used as a mouth rinse for oral candidiasis Clinical trial ended in 2008, with no results published (ClinicalTrials.gov Identifier NCT0065997) [ 90 , 91 ] CZEN-002 Derived from a melanocyte-stimulating hormone and works as a membrane disruptive agent, as well as disruption of cAMP signaling pathways and immunomodulation, such as the suppression of TNFα production Vulvovaginal candidiasis, phase IIb Relief from vaginal candidiasis with positive results: a phase I/II clinical trial reported 88.2% and 87.5% cure, but no follow-up trial ( https://www.eurekalert.org/news-releases/796451 —accessed October 2023) [ 143 , 147 , 149 , 150 ] …”