Tazarotene Foam in Focus
Topical tazarotene is commercially available in cream, gel, and foam formulations. Tazarotene foam 0.1% was FDA approved in 2012 for the treatment of acne vulgaris in patients 12 years and older. However, the product was recently relaunched to the market and therefore warrants discussion.
Similar to other retinoids, topical tazarotene has been associated with the potential for application-site irritation. This aqueous foam formulation of tazarotene was designed for ease of application and to attempt to impart moisturizing effects to offset potential irritation. It contains noncomedogenic light mineral oil, which is an emollient. The foam spreads easily, including on hair-bearing skin, with demonstrated penetration of the active drug into the epidermis and dermis. Nonetheless, compared to the gel formulation of tazarotene, the foam formulation was associated with reduced systemic exposure.10
The tazarotene foam formulation does not contain alcohol, fragrance, propylene glycol, or parabens. Clinical trial participants, blinded to whether they were on active treatment or vehicle foam, consistently rated the foam formulation favorably for ease of application and spreadability, lack of stickiness or residue, and moisturizing effect. The foam vehicle is suggested to increase compliance and satisfaction in some patients.11The efficacy and tolerability of tazarotene foam 0.1% was investigated in 2 randomized, double-blind, vehicle-controlled, parallel-group studies in the United States and Canada.12 The studies involved participants aged 2 to 45 years who were randomized to receive treatment with either tazarotene foam 0.1% or vehicle foam once daily for 12 weeks (N=1486). Lesion counts, investigator static global assessment, and subject global assessment were evaluated at baseline and at weeks 2, 4, 8, and 12. At week 12, mean reduction from baseline in noninflammatory lesions was 55.9% for active treatment, mean reduction in inflammatory lesions was 56.1%, and mean total lesion reduction was 56% compared to mean reductions of 37.7%, 45.3%, and 40.8%, respectively, for vehicle. In all, 28.2% of participants achieved treatment success with active treatment compared to 14.7% of controls. There was a greater proportion of active-treatment participants with investigator static global assessment scores of 0 or 1 compared to vehicle. The only adverse events reported by more than 5% of participants in the active-treatment groups in both studies were application-site skin irritation and dryness.12
Topical Minocycline
Systemic minocycline is the most commonly prescribed oral antibiotic for acne management.13 Despite its widespread use, it is not without potential safety concerns. Minocycline is distinct among tetracyclines for posing a small risk for systemic lupus erythematosus and autoimmune TEAE.Gastrointestinal side effects and bluish discoloration also are reported.14 Topical application of minocycline for acne would optimize the therapeutic effect while reducing systemic effects. FMX101 4%, an investigational minocycline foam, is being studied for the treatment of moderate to severe acne.
In a pharmacokinetic study, minocycline exposure was 730- to 765-times lower with foam application vs oral minocycline.15 No evidence of minocycline accumulation was identified over the 21 days of application of minocycline foam 4%. Minocycline foam 4% appeared to be safe and well tolerated, without serious TEAEs, treatment-related TEAEs, or TEAEs that led to treatment discontinuation.15
In 2 identical phase 3 studies in which 961 participants were randomized (2:1) to once-daily minocycline foam 4% or foam vehicle for 12 weeks, participants in the active-treatment group demonstrated a significantly greater reduction in both inflammatory and noninflammatory lesions in both studies (both P<.05) and a greater rate of treatment success (≥2 point reduction in IGA and score of 0 [clear] or 1 [almost clear]) in 1 study. Treatment was generally safe and well tolerated, with skin-related adverse events reported in fewer than 1% of participants receiving active treatment.16
In an open-label safety extension study that enrolled 657 patients, treatment with FMX101 continued for as long as 40 weeks.17 In total, 291 participants completed 52 weeks of therapy. Rates and types of reported TEAEs in the open-label extension phase were similar to those seen in the phase 3 trials. Application-site TEAEs occurred in fewer than 2% of participants. Participants reported a high level of treatment satisfaction at week 52.17
In a more recent phase 3 study, 1507 participants were randomized (1:1) to once-daily minocycline foam 4% or foam vehicle for 12 weeks to further evaluate the efficacy and safety of FMX101 4% for moderate to severe acne vulgaris.18 The study met both primary end points: absolute change from baseline in the inflammatory lesion count (−16.93 vs −13.40; P<.0001) and the noninflammatory lesion count (−18.80 vs −15.89; P<.05), as well as percentage of participants with IGA treatment success at week 12 (30.80% vs 19.63%; P<.0001). The percentage reduction in the inflammatory lesion count was statistically significantly greater for minocycline foam 4% compared to vehicle as early as week 3 (P<.0001). The safety profile was found to be consistent with the 2 earlier phase 3 studies.18