madman
Super Moderator
Abstract
Introduction: The efficacy of clascoterone cream was demonstrated in two-phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects. Its safety profile allowed it to be approved for treating patients as young as 12 years old. During clinical trials, the occurrence of local skin reactions (edema, erythema, pruritus, dryness) was similar to treatment with vehicle alone.
Areas covered: All publications describing the clinical development of clascoterone cream (cortexolone 17α-propionate) are reviewed and discussed in relation to existing topical and systemic therapies for acne vulgaris.
Expert opinion: Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris. Topical clascoterone 1% cream represents the first new type of therapy for acne treatment in almost 40 years and may become first-line therapy.
Article highlights:
Acne vulgaris is a chronic inflammatory dermatosis of the face and torso and one of the most prevalent skin diseases, affecting nearly 10% of the global population.
Androgens are hormones that regulate sebum production and play a key role in acne pathogenesis, contributing to symptom onset and persistence.
Clascoterone (cortexolone 17α-propionate) is a novel topical androgen receptor inhibitor, recently approved for the treatment of acne vulgaris in patients 12 years of age or older.
Subjects in two 12-week phase 3, double-blind, controlled studies achieved significant improvements in baseline noninflammatory and inflammatory lesion counts.
The safety of topical clascoterone was demonstrated in a large 9-month extension study.
The results of a comparative study showed topical clascoterone was clinically superior to topical tretinoin for treating mild-to-moderate acne vulgaris.
1.0 Introduction
Acne vulgaris is a chronic inflammatory dermatosis of the face and torso, characterized by open or closed comedones and inflammatory lesions including papules and pustules [1]. It is one of the most prevalent diseases, affecting nearly 10% of the global population [2]. Acne commonly causes scarring that can be very difficult to correct [3] and post-inflammatory dyschromia can occur in susceptible individuals [4]. The psychosocial effects of acne are also well-known [5,6] and are associated with depression, anxiety, loneliness and have a significant negative impact on interpersonal relationships and overall quality of life [7-9]. These detrimental effects are exacerbated by being negatively judged by the community at large [10]. Treatment is dependent on disease severity and may include topical prescription and over-the-counter products (benzoyl peroxide, antibiotics, retinoids), systemic antibiotics (doxycycline, tetracycline), hormonal therapies (oral contraceptives), and dietary changes (low-glycemic index), alone or in combination [1].
Acne has a complex etiology including overproduction and changes in the composition of sebum, altered keratinization of the pilosebaceous duct with sebaceous obstruction, over-colonization by Cutibacterium acne, and inflammation. Androgens are the most important hormones regulating sebum production and play a key role in acne pathogenesis, contributing to symptom onset and persistence [11]. The sebaceous glands are the main site of hormone biosynthesis [12]. During puberty, androgens stimulate sebum production and acne formation in young men and women. Sebum secretion is mediated by the potent androgens testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and androstenedione. Current anti-androgen drug therapies include off-label use of oral contraceptives, spironolactone, flutamide, and finasteride [13]; however, their use can be associated with systemic adverse events [14,15].
Clascoterone (cortexolone 17α-propionate) is a novel topical androgen receptor inhibitor that has been developed and recently approved for the treatment of acne vulgaris in patients 12 years of age or older (Winlevi® [clascoterone] cream 1%, for topical use; Cassiopea SpA, Milan Italy) [16]. The safety and efficacy of clascoterone for the treatment of acne have been demonstrated in numerous preclinical and clinical trials described below.
3.0 Conclusion
Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris and represents the first new mechanism of action for acne treatment in almost 40 years and is an excellent antiandrogen therapy for topical use.
4.0 Expert opinion
As acne vulgaris has a complex etiology [29], a wide range of therapies have been developed to treat it [30]. The choice of therapy may be based on patient age, gender, anatomic site, ethnicity, and severity [31,32]. All therapies are effective for some patients but not all therapies work for all patients. First-line treatment for mild or moderate acne vulgaris includes topical benzoyl peroxide or a topical retinoid, or a combination of topical medications consisting of benzoyl peroxide and erythromycin or clindamycin, a retinoid, or both. Due to the possibility of the development of Cutibacterium acnes resistance, topical antibiotics must not be used as monotherapy [1]. Oral therapies for acne include antibiotics, retinoids, antiandrogens, and combined oral contraceptives, all of which may have distinct drawbacks for some patients [33]. Severe acne may require a combination of oral and topical products [1]. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. Their use may be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome [33,34]. Doxycycline and minocycline are most commonly used. Oral erythromycin and azithromycin should be used only in patients for whom tetracyclines are contraindicated. The tetracycline class may cause photosensitivity reactions [35]. Oral retinoids are contraindicated in a female patient of childbearing potential at risk of becoming pregnant due to an extremely high risk of severe birth defects [36] and topical retinoids should be used with caution if at all [37].
As hormones and especially androgens are involved in the pathogenesis of acne, the use of androgen antagonists for treating acne is a logical option. Currently, available agents include combined oral contraceptives, spironolactone, flutamide, cyproterone acetate, and finasteride [13]; however, each has disadvantages. Finasteride is a 5α-reductase inhibitor indicated for the treatment of androgenetic alopecia in men [38]. Its use is contraindicated in women who are or may potentially become pregnant due to the risk of birth defects. Flutamide and cyproterone acetate are antiandrogens indicated for the treatment of prostate cancer [39,40] but are used off-label for treating acne [1]. Due to the risk of hepatotoxicity [41,42], they should not be used unless the clinical benefit outweighs the potential risk. Cyproterone acetate is not commercially available in the United States.
Spironolactone is a synthetic 17-lactone steroid that has antagonistic effects on androgen and progesterone receptors. It is indicated for the treatment of hypertension [43] but is used off-label use for treating acne. Spironolactone can be of benefit in some female patients but randomized, controlled trials are lacking [44]. The use of spironolactone is generally avoided in men due to possible feminization effects such as gynecomastia [43,45].
Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris and represents the first new type of acne treatment in almost 40 years. It blocks circulating and locally produced testosterone and dihydrotestosterone at the androgen receptors found in the sebaceous glands, sebocytes, and dermal papilla cells [18] and effective in both male and female patients. It also inhibits the synthesis of inflammatory cytokines in sebocytes [17]. Its efficacy is similar to 5αreductase inhibitor finasteride in vitro [18].
Topical clascoterone provides the therapeutic benefit of systemic antiandrogen agents without undesirable adverse events. The efficacy of clascoterone cream was demonstrated in two-phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects and its safety profile in a 9-month extension study allowed it to be approved for treating patients as young as 12 years old. During clinical trials, it provided benefits to subjects with severe acne.
The occurrence of local skin reactions (edema, erythema, pruritus, dryness, was similar to treatment with vehicle alone.Hypothalamic-pituitary-adrenal (HPA) axis suppression was observed during one clinical trial in subjects receiving the highest dose [20] and may be associated with use over large surface areas, prolonged use, and the use of occlusive dressings [16]. There was no evidence of clinical HPA suppression, and all subjects returned to normal HPA axis function after stopping treatment. In time, clascoterone cream may become first-line therapy for treating acne vulgaris.
Introduction: The efficacy of clascoterone cream was demonstrated in two-phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects. Its safety profile allowed it to be approved for treating patients as young as 12 years old. During clinical trials, the occurrence of local skin reactions (edema, erythema, pruritus, dryness) was similar to treatment with vehicle alone.
Areas covered: All publications describing the clinical development of clascoterone cream (cortexolone 17α-propionate) are reviewed and discussed in relation to existing topical and systemic therapies for acne vulgaris.
Expert opinion: Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris. Topical clascoterone 1% cream represents the first new type of therapy for acne treatment in almost 40 years and may become first-line therapy.
Article highlights:
Acne vulgaris is a chronic inflammatory dermatosis of the face and torso and one of the most prevalent skin diseases, affecting nearly 10% of the global population.
Androgens are hormones that regulate sebum production and play a key role in acne pathogenesis, contributing to symptom onset and persistence.
Clascoterone (cortexolone 17α-propionate) is a novel topical androgen receptor inhibitor, recently approved for the treatment of acne vulgaris in patients 12 years of age or older.
Subjects in two 12-week phase 3, double-blind, controlled studies achieved significant improvements in baseline noninflammatory and inflammatory lesion counts.
The safety of topical clascoterone was demonstrated in a large 9-month extension study.
The results of a comparative study showed topical clascoterone was clinically superior to topical tretinoin for treating mild-to-moderate acne vulgaris.
1.0 Introduction
Acne vulgaris is a chronic inflammatory dermatosis of the face and torso, characterized by open or closed comedones and inflammatory lesions including papules and pustules [1]. It is one of the most prevalent diseases, affecting nearly 10% of the global population [2]. Acne commonly causes scarring that can be very difficult to correct [3] and post-inflammatory dyschromia can occur in susceptible individuals [4]. The psychosocial effects of acne are also well-known [5,6] and are associated with depression, anxiety, loneliness and have a significant negative impact on interpersonal relationships and overall quality of life [7-9]. These detrimental effects are exacerbated by being negatively judged by the community at large [10]. Treatment is dependent on disease severity and may include topical prescription and over-the-counter products (benzoyl peroxide, antibiotics, retinoids), systemic antibiotics (doxycycline, tetracycline), hormonal therapies (oral contraceptives), and dietary changes (low-glycemic index), alone or in combination [1].
Acne has a complex etiology including overproduction and changes in the composition of sebum, altered keratinization of the pilosebaceous duct with sebaceous obstruction, over-colonization by Cutibacterium acne, and inflammation. Androgens are the most important hormones regulating sebum production and play a key role in acne pathogenesis, contributing to symptom onset and persistence [11]. The sebaceous glands are the main site of hormone biosynthesis [12]. During puberty, androgens stimulate sebum production and acne formation in young men and women. Sebum secretion is mediated by the potent androgens testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and androstenedione. Current anti-androgen drug therapies include off-label use of oral contraceptives, spironolactone, flutamide, and finasteride [13]; however, their use can be associated with systemic adverse events [14,15].
Clascoterone (cortexolone 17α-propionate) is a novel topical androgen receptor inhibitor that has been developed and recently approved for the treatment of acne vulgaris in patients 12 years of age or older (Winlevi® [clascoterone] cream 1%, for topical use; Cassiopea SpA, Milan Italy) [16]. The safety and efficacy of clascoterone for the treatment of acne have been demonstrated in numerous preclinical and clinical trials described below.
3.0 Conclusion
Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris and represents the first new mechanism of action for acne treatment in almost 40 years and is an excellent antiandrogen therapy for topical use.
4.0 Expert opinion
As acne vulgaris has a complex etiology [29], a wide range of therapies have been developed to treat it [30]. The choice of therapy may be based on patient age, gender, anatomic site, ethnicity, and severity [31,32]. All therapies are effective for some patients but not all therapies work for all patients. First-line treatment for mild or moderate acne vulgaris includes topical benzoyl peroxide or a topical retinoid, or a combination of topical medications consisting of benzoyl peroxide and erythromycin or clindamycin, a retinoid, or both. Due to the possibility of the development of Cutibacterium acnes resistance, topical antibiotics must not be used as monotherapy [1]. Oral therapies for acne include antibiotics, retinoids, antiandrogens, and combined oral contraceptives, all of which may have distinct drawbacks for some patients [33]. Severe acne may require a combination of oral and topical products [1]. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. Their use may be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome [33,34]. Doxycycline and minocycline are most commonly used. Oral erythromycin and azithromycin should be used only in patients for whom tetracyclines are contraindicated. The tetracycline class may cause photosensitivity reactions [35]. Oral retinoids are contraindicated in a female patient of childbearing potential at risk of becoming pregnant due to an extremely high risk of severe birth defects [36] and topical retinoids should be used with caution if at all [37].
As hormones and especially androgens are involved in the pathogenesis of acne, the use of androgen antagonists for treating acne is a logical option. Currently, available agents include combined oral contraceptives, spironolactone, flutamide, cyproterone acetate, and finasteride [13]; however, each has disadvantages. Finasteride is a 5α-reductase inhibitor indicated for the treatment of androgenetic alopecia in men [38]. Its use is contraindicated in women who are or may potentially become pregnant due to the risk of birth defects. Flutamide and cyproterone acetate are antiandrogens indicated for the treatment of prostate cancer [39,40] but are used off-label for treating acne [1]. Due to the risk of hepatotoxicity [41,42], they should not be used unless the clinical benefit outweighs the potential risk. Cyproterone acetate is not commercially available in the United States.
Spironolactone is a synthetic 17-lactone steroid that has antagonistic effects on androgen and progesterone receptors. It is indicated for the treatment of hypertension [43] but is used off-label use for treating acne. Spironolactone can be of benefit in some female patients but randomized, controlled trials are lacking [44]. The use of spironolactone is generally avoided in men due to possible feminization effects such as gynecomastia [43,45].
Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris and represents the first new type of acne treatment in almost 40 years. It blocks circulating and locally produced testosterone and dihydrotestosterone at the androgen receptors found in the sebaceous glands, sebocytes, and dermal papilla cells [18] and effective in both male and female patients. It also inhibits the synthesis of inflammatory cytokines in sebocytes [17]. Its efficacy is similar to 5αreductase inhibitor finasteride in vitro [18].
Topical clascoterone provides the therapeutic benefit of systemic antiandrogen agents without undesirable adverse events. The efficacy of clascoterone cream was demonstrated in two-phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects and its safety profile in a 9-month extension study allowed it to be approved for treating patients as young as 12 years old. During clinical trials, it provided benefits to subjects with severe acne.
The occurrence of local skin reactions (edema, erythema, pruritus, dryness, was similar to treatment with vehicle alone.Hypothalamic-pituitary-adrenal (HPA) axis suppression was observed during one clinical trial in subjects receiving the highest dose [20] and may be associated with use over large surface areas, prolonged use, and the use of occlusive dressings [16]. There was no evidence of clinical HPA suppression, and all subjects returned to normal HPA axis function after stopping treatment. In time, clascoterone cream may become first-line therapy for treating acne vulgaris.
