NEW YORK (Reuters Health) - For individuals with acne, clascoterone cream, 1%, an androgen receptor inhibitor, seemed safe and effective in two phase III trials.
“Clascoterone is poised as a potential first-in-class therapy for acne with a new mechanism of action,” Dr. Martina Cartwright, Senior Director, Medical Affairs at Cassiopea Inc. in Lainate, Italy, told Reuters Health by email. “Oral androgen receptor inhibitors are an effective strategy for treatment of female acne but unsuitable for males due to side effects. However, because clascoterone is applied topically and metabolized quickly, systemic side effects are less likely. No serious drug-related systemic side effects were observed in these studies.”
Dr. Cartwright and colleagues assessed the efficacy and safety of the cream in two identical double-blind trials. As reported in JAMA Dermatology, a total of 1,440 patients with 30-75 inflammatory lesions and 30-100 noninflammatory lesions were randomized to treatment with clascoterone cream, 1% or vehicle cream, applying approximately 1 g to the whole face twice daily for 12 weeks. The median age was 18 and approximately 62% were female.
At week 12, treatment success rates with clascoterone cream, 1%, were 18.4% in one trial and 20.3% in the other, versus 9% and 6.5% with vehicle, respectively. In both trials, treatment with the study cream resulted in a significant reduction in absolute noninflammatory lesions from baseline to −19.4, versus -13.0 and -10.3 with vehicle.
A reduction in inflammatory lesions from baseline was also reported, with reductions to -19.3 and -20.0 with the study cream versus -15.5 and -12.6 with vehicle.
Adverse event rates were low and mostly mild; trace or mild erythema was the most common local skin reaction. Dr. Cartwright noted that a long-term open-label safety study was recently completed and data are forthcoming.
“Laboratory studies show clascoterone targets acne pathogenesis by competing with dihydrotestosterone (DHT) for binding to skin androgen receptors,” she said. “DHT is a key driver of acne in both females and males. When DHT binds to androgen receptors, genes that control sebum production and inflammation are upregulated. Clascoterone’s competition with DHT could thereby reduce DHT’s effects on these genes involved in the acne pathway.”
“By targeting more than one pathway,” she added, “clascoterone could potentially be used in combination with other topical therapies like retinoids and perhaps foster antibiotic stewardship.”
Cassiopea filed a New Drug Application with the U.S. Food and Drug Administration in 2019 with a projected Prescription Drug User Fee Act date of August 27, 2020. If approved, the company anticipates a launch soon after in the United States.
Dr. John Barbieri of the University of Pennsylvania in Philadelphia, author of a related editorial, commented by email to Reuters Health, “There is a need for studies to identify how clascoterone compares to other mainstays of acne treatment such as topical retinoids and topical antibiotics.”
“This issue is a larger problem in dermatology and medicine: We introduce new - and usually expensive - treatments into clinical practice without having sufficient data to know if they provide superior value to existing options that are often less expensive,” he said. “There is a need for studies that examine how clascoterone can complement existing acne treatments, given that it has a unique mechanism of action.”
Cassiopea funded the study. In addition to Dr. Cartwright, several coauthors are employees and others have received fees from the company.