As many as 16 million Americans have rosacea, according to the National Rosacea Society,1 but only a small fraction are being treated by dermatologists. Rosacea is a chronic condition with symptoms that ebb and flow, impacting quality of life for patients. While there are many devices and prescription topical and oral medications, there is still an unmet need for effective therapies in rosacea. The lack of therapeutic options can be equally frustrating for patients and prescribers.

The recent approval of Zilxi (minocycline) topical foam 1.5% from Menlo Therapeutics provides a new option for treating the inflammatory papules and pustules of moderate-to-severe papulopustular rosacea. It is the first minocycline product to be approved by the FDA for use in rosacea. Menlo expects that prescription Zilxi will be available in late 2020.

Focus on Formulation

Oral tetracyclines, particularly minocycline and doxycycline, are often prescribed for moderate-to-severe rosacea and can be highly effective, but their use is tempered by their risk profile, including antimicrobial resistance and gastrointestinal adverse effects.

The novel foam formulation of minocycline features proprietary Molecule Stabilizing Technology (MST), which facilitates local application and bioavailability of minocycline while preserving efficacy. This is the same vehicle in the company’s Amzeeq (minocycline) topical foam 4% for the inflammatory lesions of non-nodular moderate-to-severe acne.

Zilxi’s approval was based on its paired phase 3 clinical trials involving 1,522 adult patients with rosacea.2 In each 12-week study, subjects with inflammatory lesions of rosacea were treated once daily with Zilxi or vehicle. No other topical or systemic medication affecting the course of inflammatory lesions of rosacea was permitted during these trials. The co-primary efficacy endpoints were absolute change from baseline in inflammatory lesion counts at week 12 and the proportion of subjects with treatment success at week 12, defined as an Investigator’s Global Assessment Scale (IGA Scale) of 0 (clear) or 1 (almost clear) and at least a two-grade improvement from baseline at Week 12.

Zilxi met both co-primary endpoints in each clinical trial, demonstrating statistically significant improvements in inflammatory lesion count and IGA treatment success. There were no treatment-related serious adverse events reported. The most common adverse reaction reported by ≥1% of subjects treated with Zilxi was diarrhea, which occurred more frequently than in subjects treated with vehicle (one percent vs. none), respectively.

Additionally, facial erythema was investigated during the trials, with 40.9 percent and 48.3 percent of Zilxi patients being clear or almost clear of erythema at week 12.

Safety Validated in Extension Study

In a 40-week open-label extension trial to evaluate the long-term safety, tolerability, and efficacy of Zilxi for up to 52 weeks, the majority of the treatment-emergent adverse events were considered mild or moderate.3 Zilxi continued to be associated with a decreasing number of inflammatory lesions, as well as with improvement in overall disease severity, as assessed by IGA scores throughout 52 weeks of treatment. Patient satisfaction levels were high, more than 80 percent of all subjects were either satisfied or very satisfied with Zilxi.

Zilxi offers a new therapeutic option for rosacea patients. Its topical formulation limits potential systemic antibiotic exposure. Its ability to spread easily and its low risk of cutaneous adverse events make it a useful choice in treating patients with sensitive skin.

Disclosures: Dr. Zeichner is a consultant for Almirall, Burt’s Bees, Dermavant, Dermira, Galderma, Johnson and Johnson, L’Oreal, LEO Pharma, Menlo Therapeutics, Ortho Dermatologics, Pfizer, Sanofi/Regeneron, Sun Pharma, and Unilever.

1. NRS: “Information for Patients” https://www.rosacea.org/patients/information

2. Stein-Gold L, et al. “Minocycline 1.5% foam for the topical treatment of moderate to severe papulopustular rosacea: Results of 2 phase 3, randomized, clinical trials” J Am Acad Dermatol 2020 May;82(5):1166-1173.

3. Stein-Gold L, et al.. Open-Label Extension Study Evaluating the Long-Term Safety, Efficacy, and Tolerability of FMX103 1.5% Topical Minocycline Foam in the Treatment of Moderate-to-Severe Facial Papulopustular Rosacea, Presented at: American Academy of Dermatology virtual meeting 2020. Poster No. 17800