DISCUSSION
The efficacy of 1% clascoterone cream applied topically twice daily for 12 weeks for the treatment of facial acne vulgaris remained superior compared with vehicle treatment in patients aged 12 and older. The primary and secondary efficacy endpoints were met. Topical 1% clascoterone cream was well tolerated, with a comparable safety profile to that of vehicle; no new safety concerns were identified. The majority of TEAEs were mild or moderate in severity; the most common were nasopharyngitis, headache, and oropharyngeal pain. The majority of LSRs were minimal or mild in severity. The incidence of treatment-related TEAEs was low (1.7% for 1% clascoterone cream vs 3.1% for vehicle cream), and no serious TEAE was considered related to study treatment.
There is considerable evidence on the role of androgens in the pathogenesis of acne. Available options for antiandrogen therapy include inhibition of androgen receptors (androgen receptor blockers such as oral spironolactone, flutamide, and cyproterone acetate) and/or inhibition of androgen production by the ovary or adrenal gland (oral contraceptives and lowdose glucocorticoids).12,15 Several clinical trials have assessed the efficacy of combined oral contraceptives (COCs) in reducing both inflammatory and comedonal lesion counts in patients with acne and linked this to their antiandrogenic properties.12 However, despite being effective, the oral therapies targeting the androgen pathway are associated with systemic adverse events and are not indicated as monotherapy4; moreover, COCs and spironolactone are recommended only for women.12,16 The use of spironolactone can also cause menstrual irregularities, low blood pressure, and breast tenderness in women,17 and is contraindicated during pregnancy due to the increased risk of hypospadias and feminization of a male fetus.4
Clascoterone is the first topical androgen receptor inhibitor to be approved by the FDA.18 Topical 1% clascoterone represents a novel mechanism of action for the treatment of acne and is the first topical agent targeting the hormonal pathway that may be used safely in males.19 Clascoterone cream is applied topically, and serious drug-related systemic side effects were not observed in this analysis or in previous studies.2,20,21 Clascoterone is metabolized quickly, and the primary metabolite, cortexolone, is inactive. These properties support local action with minimal systemic exposure and side effects.20 Antiandrogenic effects such as reduced libido or feminization in male participants were not observed.19 Currently, 1% clascoterone cream is the only approved topical antiandrogen treatment for acne.
The design of the phase 3 studies excluded patients with concomitant use of other anti-acne medications.2 Clascoterone cream should be investigated for potential use as a first-line foundation medication in conjunction with other existing acne topical and/or oral therapies including retinoids, benzoyl peroxide, and antibiotics. Additionally, impact of clascoterone use on quality of life was not assessed and should be considered for future trials.
The favorable efficacy and safety profiles of topical 1% clascoterone cream for the treatment of facial acne vulgaris were confirmed in patients aged ≥12 years. Frequencies of LSRs were low, and the majority were mild in severity. Further studies are needed to investigate the efficacy and safety of 1% clascoterone cream in combination with other topical acne medications.
There is considerable evidence on the role of androgens in the pathogenesis of acne. Available options for antiandrogen therapy include inhibition of androgen receptors (androgen receptor blockers such as oral spironolactone, flutamide, and cyproterone acetate) and/or inhibition of androgen production by the ovary or adrenal gland (oral contraceptives and lowdose glucocorticoids).12,15 Several clinical trials have assessed the efficacy of combined oral contraceptives (COCs) in reducing both inflammatory and comedonal lesion counts in patients with acne and linked this to their antiandrogenic properties.12 However, despite being effective, the oral therapies targeting the androgen pathway are associated with systemic adverse events and are not indicated as monotherapy4; moreover, COCs and spironolactone are recommended only for women.12,16 The use of spironolactone can also cause menstrual irregularities, low blood pressure, and breast tenderness in women,17 and is contraindicated during pregnancy due to the increased risk of hypospadias and feminization of a male fetus.4
Clascoterone is the first topical androgen receptor inhibitor to be approved by the FDA.18 Topical 1% clascoterone represents a novel mechanism of action for the treatment of acne and is the first topical agent targeting the hormonal pathway that may be used safely in males.19 Clascoterone cream is applied topically, and serious drug-related systemic side effects were not observed in this analysis or in previous studies.2,20,21 Clascoterone is metabolized quickly, and the primary metabolite, cortexolone, is inactive. These properties support local action with minimal systemic exposure and side effects.20 Antiandrogenic effects such as reduced libido or feminization in male participants were not observed.19 Currently, 1% clascoterone cream is the only approved topical antiandrogen treatment for acne.
The design of the phase 3 studies excluded patients with concomitant use of other anti-acne medications.2 Clascoterone cream should be investigated for potential use as a first-line foundation medication in conjunction with other existing acne topical and/or oral therapies including retinoids, benzoyl peroxide, and antibiotics. Additionally, impact of clascoterone use on quality of life was not assessed and should be considered for future trials.
The favorable efficacy and safety profiles of topical 1% clascoterone cream for the treatment of facial acne vulgaris were confirmed in patients aged ≥12 years. Frequencies of LSRs were low, and the majority were mild in severity. Further studies are needed to investigate the efficacy and safety of 1% clascoterone cream in combination with other topical acne medications.
DISCLOSURES
AAH, LFE, LSG, DT, SV, and YM were study investigators. AAH, LFE, and LSG were also compensated advisors to Cassiopea; DT served in the past as a consultant to Cassiopea, Inc. AAH is an employee of the McGovern Medical School of The University of Texas Health Science Center in Houston, which received compensation from Cassiopea S.p.A. for study participation; she also received an honorarium for serving on the Cassiopea advisory board; all research grant funds were paid to her institution. LFE is an employee of the University of California San Diego, which received compensation from Cassiopea S.p.A. for study participation; he has also served as an investigator, advisor, or consultant for Almirall, Galderma Laboratories, L’Oreal, and Ortho Dermatologics. DT is an employee of the College of Medicine at The Pennsylvania State University in Hershey, which received compensation from Cassiopea S.p.A. for study participation; she has also received honoraria from Galderma Laboratories, and Novartis. LSG is an employee of the Henry Ford Health System in Detroit, Michigan, which received compensation from Cassiopea S.p.A. for study participation; she has also received personal fees for advisory, speaking, consulting, research, and/or other ties with Almirall, Foamix, Galderma Laboratories, Novartis, Sol-Gel, and Sun Pharmaceuticals. MC is employed as the Vice President, Medical Affairs at Novan Inc.; was employed as the senior director of medical affairs for Cassiopea, Inc.; received personal fees as a consultant from Cassiopea S.p.A.; receives personal fees as an adjunct faculty member from the University of Arizona; holds stock options in Cassiopea S.p.A.; and was a previously contracted employee of Anacor-Pfizer and consultant to Menlo Therapeutics, NICO Corporation, and Abbott Nutrition. LM is an employee of Cassiopea S.p.A., and holds stock options in the company. EF was an employee of Cassiopea S.p.A. JH is an employee of Pharmapace Inc. NS is an employee of Sun Pharmaceutical Industries, Inc. AM is employed as the chief medical officer for Cassiopea S.p.A., and holds stock options in the company; is a board member of Cassiopea S.p.A.; and has served as the chief medical officer of Cosmo Pharmaceuticals.
Funding: The studies and analyses were funded by Cassiopea S.p.A. Medical writing and editorial support were provided by Elisabetta Lauretti PhD of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc.
Funding: The studies and analyses were funded by Cassiopea S.p.A. Medical writing and editorial support were provided by Elisabetta Lauretti PhD of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc.
