乌鸦传媒

WASHINGTON -- Clascoterone topical cream 1% was an effective and safe treatment for patients with moderate to severe acne, according to researchers here.

The pooled efficacy results from showed that 17.5% of the clascoterone topical cream group and 5.8% of the vehicle participants had a 2-point reduction in Investigator's Global Assessment (IGA) scale scores to clear (o) or almost clear (1) at 12 weeks, according to Adelaide Hebert, MD, of the University of Texas McGovern Medical School in Houston, and colleagues.

The absolute change in the inflammatory lesions at 12 weeks was -19.8% among the clascoterone topical cream group and -13.9% for the vehicle group. The absolute change in noninflammatory lesions count at 12 weeks was about -19% for the clascoterone group and about -11% for the vehicle group, Hebert reported at the American Academy of Dermatology meeting.

Clascoterone interferes with androgen receptor activation. Two formulations are under development by the Italian firm Cassiopea, which sponsored the current studies. The 1% cream (proposed trade name Winlevi) is being evaluated for treating acne, said Hebert; a 7.5%-strength product (to be sold as Breezula) is under development for .

"This is important because clascoterone has a molecular structure that looks a lot like (DHT) as well as spironolactone, and we know the effects of these two agents, both on the skin and other endocrinologically impacted organs. So focusing on a topical androgen receptor inhibitor for acne ... has value for all of us in dermatology," Hebert said.

Clascoterone is metabolized by plasma esterases to cortexolone and cortexolone 21-propionate, and quickly hydrolyzed by the skin. The metabolites exhibit weak glucocorticoid characteristics and minimal antiandrogen activity, neither of which seem very significant in the scheme of acne management. The inactive metabolites are actually found in only minimal concentrations when this product is delivered topically, Hebert emphasized.

"Clascoterone is a strong topical androgen receptor inhibitor; you see that it impacts multiple steps in acne pathogenesis," she explained. "It not only targets the androgen receptor in sebocytes and hair papilla cells, it also intervenes at multiple points in the cascade of acne pathogenesis. It actually inhibits the dihydrotestosterone-stimulated signaling downstream at the androgen receptor, thus down regulating the sebum production, as well as inflammatory cytokines."

The researchers evaluated 1,440 patients with moderate-to-severe acne at 112 medical sites in Europe and the U.S. Participants were randomized 1:1 to the clascoterone group (n=722) and the vehicle group (n=718). All participants were at least age 9 years.

Participants applied the topical cream two times a day in the morning and in the evening over 12 weeks. Over a 9-month period, participants were evaluated for an open -label safety label extension.

Participants who were eligible for the trials included nonpregnant women; women had to be surgically sterile, post-menopausal, or using very effective birth control, have an Investigator's Global Assessment Score of 3 (moderate) or 4 (severe), and have facial vulgaris with 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions.

The authors reported that treatment-emergent adverse events (TEAEs) were among 12.7% of the vehicle group, but <1% were severe and only 4.3% were moderate. There were TEAEs among 11.4% of the clascoterone group, but none of the events were severe and only 2.6% were moderate.

The most common local skin reaction was erythema/reddening, and most cases were mild or minimal, according to the authors.

Cassiopea plans to submit a new drug application to the FDA for the acne indication later in 2019, Herbert stated.