Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne

Abstract

IMPORTANCE Acne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive. OBJECTIVE To assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26). DESIGN, SETTING, AND PARTICIPANTS Two identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator's Global Assessment scale. Participants were enrolled if they had 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions. INTERVENTIONS Patients were randomized to treatment with clascoterone cream, 1%, or vehicle cream and applied approximately 1 g to the whole face twice daily for 12 weeks. MAIN OUTCOMES AND MEASURES Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear), and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity. RESULTS A total of 1440 patients were randomzied in 2 studies. In CB-03-01/25, 353 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-58] years; 221 [62.6%] female), and 355 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [9-50] years; 215 (60.6%) female); in CB-03-01/26, 369 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-50] years; 243 [65.9%] female), and 363 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [range, 11-42] years; 221 [60.9%] female). At week 12, treatment success rates in CB-03-01/25 and CB-03-01/26 with clascoterone cream, 1%, were 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P < .001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P < .001) vs 9.0% and 6.5% with vehicle, respectively. At week 12, in both CB-03-01/25 and CB-03-01/26, treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to −19.4 (point estimate difference, −6.4; 95% CI, −10.3 to −2.6; P < .001) and −19.4 (point estimate difference, −8.6; 95% CI, −12.3 to −4.9; P < .001) vs −13.0 and −10.8 with vehicle, respectively, as well as a reduction in inflammatory lesions from baseline to −19.3 (point estimate difference, −3.8; 95% CI, −6.4 to −1.3; P < .001) and −20.0 (point estimate difference, −7.4; 95% CI, −9.8 to −5.1; P < .001) vs −15.5 and −12.6 with vehicle, respectively. Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema. CONCLUSIONS AND RELEVANCE Use of clascoterone cream, 1%, for acne treatment appears to demonstrate favorable efficacy and...

Endocrinology and immunology of acne: Two sides of the same coin

“…Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema. [199] In the long-term study, 609 patients were enrolled. Overall, 110 (18.1%) F I G U R E 1 4 Pathophysiological processes involved in acne vulgaris and therapeutic targets.…”

“…Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema. [ 199 ] In the long‐term study, 609 patients were enrolled. Overall, 110 (18.1%) patients experienced 191 side effects with nasopharyngitis (n = 20) been the most frequently reported one.…”

Cortexolone 17α‐propionate for hidradenitis suppurativa

“…We read Herbert et al's article describing the efficacy of topical clascoterone (cortexolone 17α‐propionate) cream in treating acne with a keen interest into its potential applications in other dermatological diseases 1 . Whilst different pathological entities, hidradenitis suppurativa (HS) and acne share similar underlying biological processes; specifically, adnexal occlusion associated with the promotion of pro‐inflammatory cytokines 1,2 . Evidence regarding the role androgens play in the pathogenesis of HS is conflicting; however, several studies support a hormonal element reporting associations with male sex and disease severity, a high prevalence of premenstrual flares and the observation that HS is rare in children and postmenopausal women 3 .…”

“…cal clascoterone (cortexolone 17α-propionate) cream in treating acne with a keen interest into its potential applications in other dermatological diseases. 1 Whilst different pathological entities, hidradenitis suppurativa (HS) and acne share similar underlying biological processes; specifically, adnexal occlusion associated with the promotion of pro-inflammatory cytokines. 1,2 Evidence regarding the role androgens play in the pathogenesis of HS is conflicting;…”

“…3 Clascoterone is a novel topical agent that antagonizes dihydrotestosterone (DHT) through competitive binding of the androgen receptor leading to reductions in transcription of androgen-responsive genes and cytokines. 1,4 Serial studies evaluating hormonal changes in HS have shown no significant difference in testosterone levels compared to controls, suggesting that if androgens play a role in pathogenesis, their effect is more likely due to terminal conversion of testosterone to DHT which would account for both the normal levels of serum testosterone and the reported efficacy of antiandrogen therapies. 5 Clascoterone targets the conversion of testosterone to DHT and its evaluation in the use of HS may help to clarify this theory…”