Reports

ACNE VULGARIS

Clascoterone Topical Cream 1%: A Novel, Topical, Local, Selective Androgen Antagonist: Results from two Phase 3 Studies Treating Children and Adult Patients with Facial Acne Vulgaris

Presented by: Adelaide A. Hebert, MD, FAAD
Professor, Department of Dermatology
UTHealth McGovern Medical School, Houston, TX, USA

  • Clascoterone is the first topical androgen receptor inhibitor and is available in two formulations. A 1% cream is under investigation for acne, and a 7.5% solution is under investigation for androgenic alopecia.
  • There have been positive phase 3 results for acne, and positive phase 2 results for androgenic alopecia.
  • A clean safety profile has been demonstrated in more than 1,700 patients.

Clascoterone is a topical androgen receptor inhibitor under investigation for the treatment of acne. Clascoterone is hydrolyzed by the skin and metabolized to cortexolone 21-propionate and cortexolone. Both metabolites exhibit minimal anti-androgen activity and weak glucocorticoid properties [1,2]. Cortexolone is the final compound which has an established safety profile [1,2]. This agent targets androgen receptors in sebocytes and hair papilla cells within the skin’s pilosebaceous unit, intervenes at multiple and different points in acne pathogenesis, and inhibits dihydrotestosterone-stimulated signaling downstream of the androgen receptors.

  • The primary purpose of the study was to assess the efficacy of clascoterone topical 1% cream for the treatment of facial acne vulgaris in adult and pediatric populations.
  • The study assessed percent reduction in inflammatory and non-inflammatory facial lesions over a 12-week period.

Type of Study

  • Phase 3.
  • Randomized.
  • Double-blind.
  • Vehicle controlled.
  • Multicenter.
  • Two identical studies (25 & 26) at 112 sites.

Primary Purpose

  • The primary purpose of the study was to assess the efficacy of clascoterone topical 1% cream for the treatment of facial acne vulgaris in adult and pediatric populations.
  • The study assessed percent reduction in inflammatory and non-inflammatory facial lesions over a 12-week period.

Patient Populations

  • Total number of enrollees : 1,440 patients.
  • Age : ≥9 years.
  • Intent-to-treat population.
  • Inclusion criteria :
    • 30-75 inflammatory and 30-100 non-inflammatory lesions.
    • IGA 5 point scale – moderate or severe (grade 3 or 4).
  • Exclusion criteria :
    • Subject is pregnant, lactating, or is planning to become pregnant during the study period.
    • Subject has any skin pathology or condition that could interfere with the evaluation of the test products or requires the use of interfering topical or systemic therapy.
    • Subject has greater than 2 facial nodules.
    • Subject has nodulcystic acne.
    • Subject has any condition which, in the investigator’s opinion, would make it unsafe for the subject to participate in this study.
    • Subject is currently enrolled in an investigational drug or device study.
    • Subject has received an investigational drug or has been tested with an investigational device within 30 days prior to the initiation of treatment (baseline).
  • In the Table, the clinical and demographic characteristics. of the patients.

Primary Outcome Measures

  • The primary outcome measure was evaluation of any change in facial acne vulgaris, as reflected in the percent change in inflammatory lesions at week 12, to identify a change from baseline and to determine if there was a statistically significant difference between clascoterone topical 1% cream and vehicle.

Secondary Outcome Measures

  • The secondary outcome measure was assessment for change in facial acne vulgaris, as reflected in the percent change in non- inflammatory lesions at week 12, to identify a change from baseline and to determine if there was a statistically significant difference between clascoterone topical 1% cream and vehicle.

Drugs/Procedures Used

  • A 12-week phase 3 study was conducted in subjects aged ≥9 years with moderate to severe acne, followed by 9-month open label safety extension.
  • Patients were randomly assigned to clascoterone 1% topical cream or cream vehicle (1:1) for 12 weeks of treatment, during which they were to self-apply, twice daily in the morning and evening.
  • The co-primary efficacy endpoints assessed were the proportion of subjects in each group with at least a two-point reduction in IGA from baseline and IGA score of 0 (clear) or 1 (almost clear) at week 12.
  • Participants were evaluated for an absolute change from baseline in non-inflammatory lesions at week 12, as well as for an absolute change from baseline in inflammatory lesions at week 12.
  • For the outcome measure of non-inflammatory lesions at week 12, the cohort treated with clascoterone 1% topical cream demonstrated a 29.8% reduction compared to an 18.9% reduction for vehicle, reflecting a statistically significant improvement.
  • For the outcome measure of inflammatory lesions at week 12, the cohort treated with clascoterone 1% topical cream demonstrated a 46.2% reduction compared to an 32.7% reduction for vehicle, reflecting a statistically significant improvement.
  • Treatment-emergent adverse events (TEAEs) for the impacted 11.1% of the clascoterone cohort (2.6% moderate, none severe) compared to 12.7% of vehicle cohort (4.3% moderate, <1% severe). Local skin reactions consisted of mild erythema.
  • Clascoterone 1% topical cream treatment resulted in a clinically significant reduction in both inflammatory and non-inflammatory skin lesions over 12 weeks in both children and adults, thereby demonstrating efficacy.
  • Treatment with clascoterone 1% topical cream produced a low rate of TEAEs which were not generally severe, thereby demonstrating safety.

Key Messages/Clinical Perspectives

  • The phase 3 trial data for clascoterone 1% topical cream demonstrates that it is effective in the treatment of facial acne vulgaris for adult and pediatric populations aged ≥9 years.
  • The phase 3 trial data for clascoterone 1% topical cream demonstrates that it is has a tolerable safety profile when used for treatment of facial acne vulgaris for adult and pediatric populations aged ≥9 years.


REFERENCES

Presenter disclosure(s): The presenter has reported the following disclosures: Allergan, Inc.; Amgen; Anacor Pharmaceuticals, Inc.; Astellas Pharma US, Inc.; Bickel Biotechnology; Cassiopia; Celgene Corporation; Chugai Pharma; Cutanea Life Sciences; US, Department of Defense; Dermavant Sciences; Dermira; Encore Dermatology, Inc.; Galderma Laboratories, L.P.; GlaxoSmithKline; Intendis, Inc.; La Roche-Posay Laboratoire Pharmaceutique; Mayne Pharma Group; Medimetriks Pharmaceuticals, Inc.; Menarini Group; Menlo Therapeutics; Merz Pharmaceuticals, LLC; NIH; Novan; Novartis Pharmaceuticals Corp.; Onset Therapeutics  Ortho Dermatologics; Pfizer Inc.; Pharmaderm; PPD Inc.; Prim-Med; Promius Pharma, LLC; Promius Pharmaceuticals; Regeneron; Roivant Sciences; Shionogi USA; Sienna Biopharmaceuticals; Sinclair Pharma; Stiefel, a GSK company; TopMD; Valeant Pharmaceuticals International; Vanda Pharmaceuticals Inc.

Written by: Daniel Bennett, MPH

Reviewed by: Martina Lambertini, MD


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