This study provides initial clinical evidence of reductions in measured facial sebum production following treatment with clascoterone cream 1% in patients with acne. Although some systemic treatments are shown to decrease sebum production, there appear to be no other reports demonstrating this for a US Food and Drug Administration (FDA)–approved topical acne medication [6]. The clinical findings from this study recapitulate those reported from the Phase 3 clinical trials, including reductions in the numbers of noninflammatory and inflammatory lesions following 12 weeks of treatment with clascoterone cream 1% [7], and confirm the effect of clascoterone treatment on sebum production. Overall, this study expands the clinical profile of clascoterone cream 1% and helps to illuminate the mechanism of action of clascoterone in the treatment of acne.

Consistent with reductions in objective facial sebum measurements, patients using clascoterone cream 1% had significant improvements in investigator-assessed subjective facial characteristics related to sebum production, including oily appearance, shine, and pore size. Several factors including sebum production, skin elasticity, and the presence of acne may impact pore characteristics [8, 9]. Excessive sebum production is strongly implicated as a contributing factor to increased visible pore quantity and/or size, particularly in people with acne [8, 9], corroborating the association between sebum levels and pore size observed in the current study. Therefore, the clinical benefits of clascoterone cream 1% include improvements in subjective facial characteristics associated with excess sebum production, which are often reported as concerns in individuals with acne, as well as reductions in measured facial sebum levels [10, 11].

Excessive sebum production is a substantial driver of the acne pathogenesis cascade. Other topical agents approved by the FDA for acne treatment act primarily by modulating keratinocyte differentiation and/or antibacterial and anti-inflammatory actions [3] but do not act directly on sebaceous gland activity. Systemic acne medications that reduce sebum production include hormonal therapies and oral isotretinoin [6]. The reductions in sebum measurements reported in this study are consistent with those reported following treatment with systemic antiandrogens in patients with acne. In an open-label trial, treatment with an oral contraceptive led to reductions in sebum measurements from baseline by 15% after two treatment cycles (8 weeks) and 20% after four treatment cycles (16 weeks) in 177 female patients with acne [12]. Reductions in forehead sebum production by 30% were reported following treatment with an oral contraceptive in 41 patients with acne in a randomized, double-blind study [13], with other studies reporting similar results [14, 15].

Previous studies report a wide range of sebum reduction in patients with acne treated with oral isotretinoin. In a prospective study including 35 patients with acne who were treated with oral isotretinoin for 6 months, patients had an overall 36% decline in sebum levels [16], whereas overall percentage reductions of 50% to 75% or greater were reported following isotretinoin therapy in other, similar studies [17,18,19]. The wide range in reported values may be due to differences in patient characteristics, isotretinoin dosage, duration of treatment at the time of sebum assessments, and method of evaluating sebum production. The reduction in sebum measurements observed in this study following 12 weeks of treatment with clascoterone cream 1%, a topical agent, falls slightly below the range of values reported following 3–7 months of treatment with oral isotretinoin [16,17,18,19]. Isotretinoin is also associated with reports of dry lips/skin that are not observed with clascoterone cream 1% [20]. It will be instructive to compare the percentage reductions in sebum values following ≥6 months of treatment with clascoterone cream 1% with those reported for oral isotretinoin.

This study had several potential limitations. Due to the open-label, non-comparative design of the study, it is difficult to attribute the observed effects solely to use of clascoterone cream 1%. However, participants were not permitted to initiate any other skincare products or medications, including prescription and over-the-counter treatments, cleansers, moisturizers, and cosmetics, while participating in the study. Additionally, although the sample size was somewhat small, the data were internally consistent and supported the use of appropriate tests for statistical significance. Although the sebumeter is a validated method commonly used in cosmetic and medical research to quantify changes in casual sebum levels on the skin [21], readings can be affected by external variables. The research center attempted to perform sebum measurements for all patients at the same time of day and under standard environmental conditions (e.g., temperature, humidity) to ensure consistency; however, sebum measurements may have been impacted by the thoroughness of face washing prior to each visit, or other external factors such as fluctuations in weather. Sebumeter measurements can also be user dependent, and the same investigator performed all measurements at each visit to minimize this source of variability. Despite these measures, fluctuations in sebumeter measurements were observed between visits during the study; however, the overall trend indicates that clascoterone cream 1% treatment does decrease sebum production.

Interestingly, improvements in the severity of acne as determined by the reduction in acne lesions preceded the observed decrease in sebum measurements. This may be due to several factors, including fluctuations in sebum measurements and the potential contribution of other pathogenic factors (e.g., reduction in inflammation, microbiome changes) to the observed lesion count reductions. The full 52-week study will also explore changes in the facial microbiome following treatment with clascoterone cream 1%, which will further expand our understanding of the mechanism of action of clascoterone in the treatment of acne vulgaris.