Rosacea: A Closer Look at the Latest Treatment Options

When it comes to the topical treatment of rosacea, new treatment options offer the potential to improve outcomes for patients. The latest options for rosacea treatment are based on well-known drugs in novel formulations that optimize outcomes while enhancing tolerability.

Newer Options

Encapsulated benzoyl peroxide cream 5% (Epsolay, Galderma) is a somewhat unexpected treatment for rosacea. The oxidizing agent previously had been tried for the treatment of rosacea but was considered too irritating for use in most patients. However, this novel topical cream formulation for rosacea uses a silica encapsulation process to coat the benzoyl peroxide molecules. The silica shells facilitate slow and deliberate delivery of benzoyl peroxide to the skin.

Encapsulated benzoyl peroxide cream 5% was tested in two 12-week, randomized, double-blind, vehicle cream-controlled phase 3 trials, involving 733 adult subjects with moderate to severe rosacea.¹ Subjects were randomized 2:1 to once daily application of the active cream or vehicle.

The primary outcome measure was the percentage of subjects who achieved Investigator’s Global Assessment score of clear or almost clear. In study 1, 43.5% of active treatment subjects achieved the primary endpoint, and in study 2, 50.1% of active treatment subjects achieved the primary endpoint. This compares to 16.1% and 25.9% of vehicle subjects, respectively. Lesion counts for active treatment were -17.4 and -20.3, respectively, compared to -9.5 and -13.3 for controls, respectively.¹

Of note, there were no treatment-related serious adverse events associated with the cream. Subjects in both the active treatment and the control groups reported similar ratings for local tolerability, suggesting that the encapsulated benzoyl peroxide cream formulation was not associated with notable skin irritation.¹ Furthermore, patients reported that background redness and baseline irritation diminished with use of the formulation.

A long-term, open-label extension study showed that continued treatment with active cream for up to 40 weeks resulted in increased and persistent improvements in IGA scores. Findings indicated a favorable safety and tolerability profile.²

Topical benzoyl peroxide is just one in a growing class of topical antimicrobials formulated for the treatment of rosacea. Topical antimicrobial medications for rosacea most often are used for their anti-inflammatory properties rather than their bactericidal effects.

Somewhat new to market is topical minocycline foam 1.5% (Zilxi, Journey Medical Corp.), which has been shown to be very effective in controlling rosacea. Interestingly, with use of topically applied minocycline, we typically do not see the side effects that may be seen when the drug is administered systemically.³ In fact, a maximal use study determined that there is minimal systemic exposure when minocycline foam 1.5% is applied topically. In phase 3 clinical trials, subjects treated with topical minocycline foam 1.5% had significantly greater reductions in inflammatory lesion counts and had higher rates of IGA success, compared to vehicle controls. Active treatment was well-tolerated, and no serious treatment-emergent adverse events were reported.⁴

The favorable safety profile of topical minocycline foam 1.5% that was seen in the phase 3 trials was confirmed in a 40-week open-label extension study, in which active treatment was associated with greater than 82% reduction in inflammatory lesions from baseline. A similar proportion of subjects reported being “satisfied” or “very satisfied” with treatment. Local tolerability symptoms improved throughout the study period.⁵

For those patients with rosacea who are candidates for oral treatment, low-dose, minocycline extended-release oral capsules (DFD-29, Journey Medical Corp.) show promise. In a phase 2 trial, DFD-29 40mg was associated with statistically significantly higher levels of IGA treatment success (66%) than placebo (11.5%), DEF-29 20mg (31.9%), or doxycycline 40mg (33.3%). Of note, low-dose, minocycline extended-release oral capsules appear to confer benefit without providing an antibiotic effect. In fact, recorded plasma concentrations among treatment patients were below the predicted antimicrobial threshold for the treatment of rosacea.⁶

Expanded, Responsible Options

The World Health Organization has identified antimicrobial resistance as a global health threat, and other organizations and professional societies—including the American Acne and Rosacea Society—have echoed the call for antibiotic stewardship. Dermatologists must use topical and systemic antimicrobials responsibly. Relatively new formulations harness the benefits of benzoyl peroxide and minocycline with good tolerability and, more importantly, no or minimal antibiotic action. Hopefully, the anti-inflammatory effects of these agents in specialty formulations can calm the symptoms of rosacea and yield control of the disease without encouraging the development of resistance.

Based in part on a presentation given at DERM2023.

1. Bhatia ND, Werschler WP, Baldwin H, et al. Efficacy and safety of microencapsulated benzoyl peroxide cream, 5%, in rosacea: Results from two phase III, randomized, vehicle-controlled trials. J Clin Aesthet Dermatol. 2023;16(8):34-40.

2. Werschler WP, Sugarman J, Bhatia N, et al. Long-term efficacy and safety of microencapsulated benzoyl peroxide cream, 5%, in rosacea: Results from an extension of two phase III, vehicle-controlled trials. J Clin Aesthet Dermatol. 2023;16(8):27-33.

3. Jones TM, Stuart I. Safety and pharmacokinetics of FMX103 (1.5% Minocycline Topical Foam) in subjects with moderate-to-severe papulopustular rosacea under maximum-use treatment conditions. J Clin Aesthet Dermatol. 2021;14(3):E53-E57.

4. Gold LS, Del Rosso JQ, Kircik 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;82(5):1166-1173. doi:10.1016/j.jaad.2020.01.043

5. Stein Gold L, Del Rosso JQ, Kircik L, et al. Open-label extension study evaluating long-term safety and efficacy of FMX103 1.5% minocycline topical foam for the treatment of moderate-to-severe papulopustular rosacea. J Clin Aesthet Dermatol. 2020;13(11):44-49.

6. Tsianakas A, Pieber T, Baldwin H, et al. Minocycline extended-release comparison with doxycycline for the treatment of rosacea: A randomized, head-to-head, clinical trial. J Clin Aesthet Dermatol. 2021;14(12):16-23.