Novel acne cream seeks FDA approval

“If the medication adds significantly to clearing … as expected from the trials, we will be very happy to have another tool in our box," says Dr. Eichenfield, M.D.

Dr. Eichenfield

In August, Italian pharmaceutical company Cassiopea SpA submitted a New Drug Application to the FDA for marketing
approval of clascoterone cream 1% for acne treatment. If approved, the topical androgen receptor inhibitor would be the first new mechanism of action in acne in nearly four decades.

READ MORE: Recent developments in acne

Clascoterone 1% cream is in late stage development for acne treatment and in a higher strength solution for androgenetic alopecia. Once applied to the skin’s surface, clascoterone penetrates the skin to reach the androgen receptors within the sebaceous glands and hair follicles, according to a Cassiopea news release announcing the New Drug Application on August 20, 2019.

“Clascoterone is an exciting new drug, as it is based on a novel mechanism of action for a topical agent, targeting androgen receptors,” says Lawrence Eichenfield, M.D., chief of Pediatric and Adolescent Dermatology at Rady Children’s Hospital - San Diego, and a clascoterone 1% cream study investigator.

“The cream is designed as a small molecule to target the sebaceous gland. We know that androgen receptors mediate dihydrotestosterone, which appears to be an important driver of acne.”

Clascoterone acts as a local, selective androgen inhibitor, limiting the acnegenic effects of androgens on sebum production and inflammation, according to Cassiopea SpA.

Clascoterone quickly metabolizes to cortexolone, a naturally occurring metabolite found in human tissues, cells, blood and urine. Due to its rapid metabolism and local activity, clascoterone does not produce worrying systemic side effects, according to the company.

THE SCIENCE
In a phase 3 open label study of subjects looking at safety and efficacy of up to one year of clascoterone topical cream treatment for acne, researchers found no hormonal imbalance in the patients who applied the topical to both the face and trunk. More than 400 patients received clascoterone therapy for at least 26 weeks and 119 subjects applied the topical for 52 weeks, total, according to the company press release.

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In that study, about 18% of patients reported treatment-emergent adverse events, including the most frequently reported: nasopharyngitis and upper respiratory tract infection. Investigators documented local skin reactions, including redness and dryness in approximately 24% of patients faces.

According to Martina Cartwright, Ph.D., senior director of medical affairs at Cassiopea, “The incidence of new or worsening erythema was 12.2% in those treated with clascoterone cream 1% versus 15.3% in vehicle, and new or worsening scaling and dryness rates were 10.5% (in those treated with clascoterone cream)
and 10.3% (in vehicle).”

Fifty-seven percent of patients achieved an Investigator Global Assessment (IGA) with at least a two-step improvement resulting in a 0, or clear, and 62% achieved 1, or almost clear, at week 52.

Researchers, including Cassiopea SpA employees, found that when compared to the androgen receptor antagonist spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes, according to a study published May 2019 in the Journal of Drugs in Dermatology.

RELATED: Acne patients open to antibiotic-free treatment

In an article published July 2019 in Cutis, author and dermatologist Leon Kircik, M.D., writes, “Recently approved sarecycline (a tetracycline antibiotic) is the first new chemical entity approved for acne in several years. It might be followed in the coming years by other new actives, including clascoterone and cannabidiol (CBD).”

OPTIMAL USE
What remains to be seen is how clascoterone 1% cream will fit into acne treatment, according to Dr. Eichenfield.

“Clinical studies of new topical drugs are done as monotherapy…,” Dr. Eichenfield tells Dermatology Times. “We will have to see if this is best as an alternative first line agent or along with topical retinoids, benzoyl peroxide, antibiotics (oral or topical) and other hormonal therapies. It could complement all of these therapies.”

Clascoterone 1% cream could be good news for acne patients and the doctors who treat them, according to Dr. Eichenfield.

“If the medication adds significantly to clearing as compared to other medications or in addition to other medications, as expected from the trials, we will be very happy to have another tool in our box,” he says. “‘Acneologists have long known the importance of sebaceous glands and hormonal stimulation impact on acne pathogenesis.”

Disclosures:

Dr. Eichenfield has consulting and/or research ties to Allergan, Almirall, Cassiopeia, Dr. Reddy, DS Laboratories, Galderma, LEO Pharma, Lilly, Novan, Otsuka Pharmaceutical Co., Pfizer, Sanofi-Regeneron, Ortho Dermatologics/Valeant, and Vyome