With the FDA approval of Cassiopea SpA’s Winlevi (clascoterone cream 1%) to treat acne in patients 12 years and older, the European company hailed it as the first acne drug in 40 years with a new mechanism of action.

Winlevi, for use twice daily, is a non-antibiotic targeting androgen receptors that drive sebum production (excess oil) and inflammation. Cassiopea said Winlevi’s exact mechanism of action is unknown but added that lab studies suggest the active ingredient, clascoterone, competes with androgens, specifically dihydrotestosterone, to bind to androgen receptors within the sebaceous gland and hair follicles.

Michael Gold, Winlevi clinical trial investigator

Michael Gold, a clinical assistant professor at the Vanderbilt University School of Medicine and a Winlevi clinical trial investigator told BioWorld that other acne treatments were always missing sebum production, “which is 99% of my acne patients who produce too much oil activity. It’s why they get acne.”

Winlevi is a new class of drug, different than traditional acne treatments such as tetracycline and doxycycline, Gold added. Androgen receptor inhibitors limit sebum production and inflammation, the company said, adding that the pivotal trials showed reductions in acne lesions. Winlevi was well tolerated when used twice daily.

Lainate, Italy-based Cassiopea said it expects Winlevi to become available in the U.S. in early 2021.

Pricing will be disclosed in the fourth quarter of 2020. On March 31, H.C. Wainwright & Co. analyst Raghuram Selvaraju wrote that Cassiopea was not planning to price the drug above $600 per patient. Selvaraju noted that recent acne drug launches, such as Aklief (trifarotene 50 mcg/g cream), a retinoid molecule, are priced in about the $475 to $550 range.

The U.S. prescription branded anti-acne drug market is $3 billion annually.

The approval was based on data from two identical placebo-controlled phase III trials of enrolled 1,440 patients with acne vulgaris. Clinical efficacy of subjects with acne vulgaris at week 12 showed success on the Investigator Global Assessment scale as 18.8% for Winlevi and 8.7% with the vehicle cream in the trial 1 and 20.9% for Winlevi vs. 6.6% for the vehicle cream in trial 2. That success was defined as at least a 2-point reduction in IGA compared to baseline and an IGA score of 0 (clear) or 1 (almost clear).

The company stock (SIX:SKIN) had a strong day on the Six Swiss Exchange in Zurich as shares surged to close upward 15.22% at $53 per share on Aug. 26.

Cosmo Pharmaceuticals SA spun Cassiopea out its dermatology unit in 2015. The move was prompted by a recognition that the two businesses had little in common. Cosmo is developing treatments for gastrointestinal diseases.

Acne lesion types. © 2017 Clarivate Analytics. All rights reserved.

Acne affects about 50 million in the U.S. annually and is the most common dermatologic skin disease. More than half, 57%, of all cases of acne vulgaris in the U.S., France, Germany, Italy, Spain, the U.K. and Japan occur in females, according to DRG.

Possible competitors in development

The acne treatment field is crowded and there are plenty of treatments in development.

Menlo Therapeutics Inc., of Bridgewater, N.J., has FCD-105, a bacteriostatic and anti-inflammatory minocycline plus the retinoid adapalene for treating moderate to severe acne vulgaris in a phase II study. In June, the company said FCD-105 produced an Investigator’s Global Assessment of 0 or 1 and at least a 2-grade improvement from baseline to week 12 in 35.9% of patients compared to 15.7% of patients in the vehicle treatment group (p=0.0003); absolute reduction in inflammatory lesion counts at week 12 was -19.4 (-64.1%) for the FCD-105 and -15.58 (-50.9%) for the vehicle treatment group (p=0.0020).

In December, the FDA approved Bausch Health Companies Inc.’s NDA for Arazlo (tazarotene) Lotion, a topical treatment for patients age 9 and older that binds to retinoic acid receptors. Arazlo is the first tazarotene acne treatment available in a lotion form, according to Ortho Dermatologics, Bausch’s dermatology business. In January, the Journal of Drugs in Dermatology published results from two studies showing 25.5% and 29.6% of patients achieved treatment success on first primary endpoint, at least a 2-grade improvement in Evaluator’s Global Severity Score measured at week 12, compared to placebo rates of 13% and 17.3%, respectively (p<0.001 for both studies).

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