Novel androgen receptor inhibitor cream also had low, mostly mild adverse events

Use of the novel topical androgen receptor inhibitor, clascoterone cream 1%, was associated with favorable efficacy and safety profiles compared to vehicle cream in patients with moderate to severe facial acne enrolled in 2 phase III clinical trials.

After 12-weeks of treatment with clascoterone (cortexolone 17 α-proprionate) cream, 18.4% and 20.3%, respectively, of patients in active treatment arms of the two studies had clear or almost clear skin and a 2-grade or greater improvement in acne presentation from baseline.

Adverse event rates were low and mostly mild, with trace or mild erythema being the predominant local skin reaction in the identical, multicenter, vehicle-controlled randomized trials, published online April 22 in JAMA Dermatology.

Topical clascoterone cream, 1%, is under investigation as a first-in-class treatment for males and females targeting the hormonal pathogenesis of acne.

Late last fall, the U.S. Food and Drug Administration (FDA) accepted pharmaceutical company Cassiopea Spa’s (Lainate, Italy) application for its review under New Drug Application (NDA) status as a novel acne treatment. The company reported that the FDA has set late August of this year as the action date for the review.

Researcher Adelaide Herbert, MD, of the University of Texas Health Science Center, Houston, and colleagues, wrote that androgen inhibition is an accepted strategy for the treatment of acne in females, adding that the combined oral contraceptives norgestimate and norethindrone are approved by the FDA for the treatment of acne in females. The aldosterone inhibitor and AR blocker spironolactone is also used off-label to treat acne in females.

“Both (oral contraceptives) and spironolactone are associated with systemic adverse effects, are contraindicated in pregnancy, and are unsuitable for use in males with acne,” they wrote. “Other AR inhibitors and/or anti-androgens have not been approved for the treatment of acne in males.”

The twin studies included a total of 1,440 patients with moderate-to-severe acne, randomized to topical treatment with either clascoterone cream, 1%, or vehicle cream, applied to the face twice daily for 12 weeks.

The median age of the patients in the two studies was around 18 years (range 9 years to 58 years) and roughly 40% to 45% of the participants were male.

Treatment success was defined as an Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear) and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity.

Among the main study findings:

  • At week 12, 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P<0.001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P<0.001) of clascoterone, 1%-treated patients achieved treatment success versus 9.0% and 6.5% in patients randomized to the vehicle cream arm of the study.
  • In both studies treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to −19.4 (point estimate difference, −6.4; 95% CI, −10.3 to −2.6; P<0.001) and −19.4 (point estimate difference, −8.6; 95%CI, −12.3 to −4.9; P<0.001) versus −13.0 and −10.8 with the vehicle cream, respectively.
  • Clascoterone cream-treated patients also achieved reduction in inflammatory lesions from baseline to −19.3 (point estimate difference, −3.8; 95CI, −6.4 to −1.3; P<0.001) and −20.0 (point estimate difference, −7.4; 95% CI, −9.8 to −5.1; P<0.001) versus −15.5 and −12.6 with the vehicle cream, respectively.

Treatment adherence was approximately 90% among patients using the clascoterone cream, 1%, “which suggests that the treatment regimen is easy to follow and suitable for general clinical practice,” Hebert and colleagues wrote.

In an editorial published with the study, John Barbieri, MD, of the University of Pennsylvania Perelman School of Medicine, wrote that while topical clascoterone “represents an exciting new therapeutic option for patients with acne, many questions remain.”

Among them, Barbieri noted, is “where clascoterone fits in our therapeutic ladder for acne treatment.”

“Although results of a small pilot study suggested that clascoterone may have similar or even superior efficacy to tretinoin cream, 0.05%, an active comparator arm was not included in these phase III trials,” Barbieri wrote. “As a result, there is a need for future studies to examine how the effectiveness and tolerability of clascoterone compare with other topical acne medications. In addition, it will be important to explore whether it has complementary benefits when used in combination with other treatments.”

It will also be important to examine whether the topical therapy has greater efficacy in certain subgroups of patients or specific acne phenotypes, and whether use can reduce reliance on oral antibiotics., Barbieri added.

“It is notable that clascoterone had good efficacy for both noninflammatory and inflammatory lesions in these trials and it may be particularly helpful for patients with more inflammatory acne that may not respond well to other topical medications,” he wrote.

A final unanswered question is whether insurance companies will cover the novel topical acne drug, Barbieri noted, given the current restrictive climate regarding acne treatment reimbursement.

“In recent years, it has been increasingly difficult to obtain coverage for both branded and generic acne products,” Barbieri noted.

“Some formularies have begun to completely exclude all topical acne treatments. This issue is particularly problematic for older patients, despite evidence that acne often persists into adulthood. As a result, it may be that many patients will experience challenges with coverage and affordability for this new medication.”

  1. Use of the novel topical androgen receptor inhibitor clascoterone cream 1% was associated with favorable efficacy and safety profiles compared to vehicle cream in patients with moderate to severe facial acne.

  2. Be aware that clascoterone is not yet approved by the FDA, but the agency has set an action date for review in late August.

Salynn Boyles, Contributing Writer, BreakingMED™

The study was funded by Cassiopea Spa, which developed clascoterone cream, 1%, which has been accepted for review under New Drug Application status by the FDA.

Researchers Adelaide Herbert, Diane Thriboutot and Linda Stein reported receiving personal fees and other fees and serving as advisors for Cassiopea Spa. Other researchers reported receiving fees or being employees of Cassiopea Spa, including principal investigator Alessandro Mazzetti, who is chief medical officer for the company.

Cat ID: 105

Topic ID: 75,105,730,105,138,192,925