Long-Term Safety and Efficacy of Twice-Daily Topical Clascoterone Cream 1% in Patients Greater Than or Equal to 12 Years of Age With Acne Vulgaris

August 2023 | Volume 22 | Issue 8 | 810 | Copyright © August 2023


Published online July 31, 2023

Lawrence F. Eichenfield MDa, Adelaide A. Hebert MDb, Linda Stein Gold MDc, Martina Cartwright PhDd, Luigi Moro PhDe, Jenny Han MSf, Nicholas Squittieri MDg, Alessandro Mazzetti MDe

aUniversity of California San Diego School of Medicine, La Jolla, CA; Rady Children’s Hospital San Diego, San Diego, CA
bUTHealth McGovern Medical School, Houston, TX
cDepartment of Dermatology, Henry Ford Medical Center, Detroit, MI
dCassiopea Inc., San Diego, CA
eCassiopea S.p.A., Lainate, Italy 
fPharmapace Inc., San Diego, CA
gSun Pharmaceutical Industries, Inc., Princeton, NJ

may be a suitable option for long-term topical treatment of both facial and truncal acne vulgaris in patients greater than or equal to 12 years of age. 

The findings from this and previous studies support clascoterone as an option for long-term treatment of acne vulgaris. Systemic exposure is low following topical clascoterone treatment;12 and systemic antiandrogen effects associated with oral androgen receptor blockers and other hormonal treatments3 were not observed in patients treated with clascoterone cream 1% in this long-term study or previous studies.1,12,13 Laboratory abnormalities were not evaluated in this study or the Phase 3 pivotal studies; shifts from normal to elevated potassium levels were observed in some patients treated with clascoterone in the Phase 1 and Phase 2 studies, although none were reported as AEs. Hypothalamic-pituitary-adrenal (HPA) axis suppression was observed in 3/42 (7%) patients treated with clascoterone in a Phase 2 safety study in patients greater than or equal to 12 years of age with moderate-to-severe acne vulgaris; HPA axis function returned to normal in all patients at follow-up 4 weeks after stopping treatment.12 During 9 additional months of clascoterone treatment, the most common new or worsening LSRs on both the face and trunk in patients greater than or equal to 12 years of age were erythema and scaling/dryness, consistent with previously published long-term findings in patients ≥ 9 years of age7 and short-term studies.1,13

These findings expand upon results from the Phase 3 pivotal studies, in which clascoterone cream 1% was significantly more efficacious vs vehicle cream after 12 weeks of treatment.1,14 In this long-term extension study, approximately half of PP patients greater than or equal to 12 years of age achieved IGA 0/1 for both the face and trunk. The proportion of patients who were clear or almost clear increased at each visit and was highest at the end of the study, indicating that clascoterone efficacy improved over time for up to 12 months in patients with moderate-to-severe acne vulgaris.

The study was designed primarily to evaluate long-term safety, and therefore, there was no ongoing comparator planned for efficacy evaluation. Additionally, concomitant acne medications  were not evaluated in this study; therefore, the safety and efficacy of combined treatment with clascoterone and other topical medications should be evaluated in future clinical studies.

CONCLUSION

Clascoterone cream 1% exhibited favorable long-term safety and efficacy during treatment up to 12 months in patients greater than or equal to 12 years of age with moderate-to-severe acne vulgaris and may be a safe and effective alternative to traditional acne medications for long-term treatment.

DISCLOSURES

LFE, AAH, and LSG were study investigators. LFE, AAH, and LSG were also compensated advisors to Cassiopea. 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. She has also received personal fees for advisory, speaking, consulting, and/or other services with Almirall, Incyte, Pfizer, Aslan, Galderma Laboratories, Novartis, and Sun Pharma. 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, Dermata, Galderma Laboratories, and Ortho Dermatologics. 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 services with Almirall, Foamix, Galderma Laboratories, Novartis, Sol-Gel, and Sun Pharma. MC is employed as the Vice President of Medical Affairs at Novan Inc.; was employed as the senior director of medical affairs at Cassiopea, Inc. at the time of the study; received personal fees as a consultant from Cassiopea S.p.A.; and receives personal fees as an adjunct faculty member from the University of Arizona. LM is an employee of Cassiopea S.p.A., and holds stock options in the company. 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; and has served as the chief medical officer of Cosmo Pharmaceuticals.

ACKNOWLEDGMENT

The authors thank the patients, investigators, and sites for their participation. The studies were funded by Cassiopea S.p.A. Medical writing and editorial support were provided by Dana Lengel PhD, of AlphaBioCom, a Red Nucleus company, and funded by Sun Pharma.

REFERENCES

  1. Hebert A, Thiboutot D, Stein Gold L, et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(6):621-630.
  2. Lynn DD, Umari T, Dunnick CA, et al. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther. 2016;7:13-25.
  3. Elsaie ML. Hormonal treatment of acne vulgaris: an update. Clin Cosmet Investig Dermatol. 2016;9:241-248. 
  4. Dart DA. Androgens have forgotten and emerging roles outside of their reproductive functions, with implications for diseases and disorders. J Endocr Disord. 2014;1(1):1005. 
  5. Piszczatoski CR, Powell J. Topical clascoterone: the first novel agent for acne vulgaris in 40 years. Clin Ther. 2021;43(10):1638-1644. 
  6. Aldactone® (spironolactone). Prescribing information. Pfizer, Inc.; 2021. 
  7. Eichenfield L, Hebert A, Gold LS, et al. Open-label, long-term extension study to evaluate the safety of clascoterone (CB-03-01) cream, 1% twice daily, in patients with acne vulgaris. J Am Acad Dermatol. 2020;83(2):477-485. 
  8. WINLEVI® (clascoterone cream 1%). Prescribing information. Sun Pharmaceutical Industries, Inc.; 2022. 
  9. Rosette C, Agan FJ, Mazzetti A, et al. Cortexolone 17alpha-propionate (clascoterone) is a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. J Drugs Dermatol. 2019;18(5):412-418. 
  10. Rosette C, Rosette N, Mazzetti A, et al. Cortexolone 17alpha-propionate (clascoterone) is an androgen receptor antagonist in dermal papilla cells in vitro. J Drugs Dermatol. 2019;18(2):197-201. 
  11. Ferraboschi P, Legnani L, Celasco G, et al. A full conformational characterization of antiandrogen cortexolone-17α-propionate and related compounds through theoretical calculations and nuclear magnetic resonance spectroscopy. MedChemComm. 2014;5(7):904-914. doi: 10.1039/C4MD00049H.
  12. Mazzetti A, Moro L, Gerloni M, et al. Pharmacokinetic profile, safety, and tolerability of clascoterone (cortexolone 17-alpha propionate, CB-03-01) topical cream, 1% in subjects with acne vulgaris: an open-label phase 2a study. J Drugs Dermatol. 2019;18(6):563. 
  13. Mazzetti A, Moro L, Gerloni M, et al. A phase 2b, randomized, double-blind vehicle controlled, dose escalation study evaluating clascoterone 0.1%, 0.5%, and 1% topical cream in subjects with facial acne. J Drugs Dermatol. 2019;18(6):570. 
  14. Hebert AA, Eichenfield LF, Thiboutot D, et al. Efficacy and safety of 1%clascoterone cream in patients aged ≥12 years with acne vulgaris. J Drugs Dermatol. 2023;22(2):174-181. doi:10.36849/JDD.7000.

AUTHOR CORRESPONDENCE

Lawrence F. Eichenfield MD leichenfield@rchsd.org
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