Topical minocycline foam for moderate to severe acne vulgaris: Phase 2 randomized double-blind, vehicle-controlled study results (2016)

To the Editor: Acne vulgaris (AV) is a chronic inflammatory skin disease that affects 80% to 90% of persons by the age of 21.1Well D. Acne vulgaris: a review of causes and treatment options.Nurse Pract. 2013; 38: 22-31Crossref Scopus (30) Google Scholar Oral antibiotics, such as tetracycline, doxycycline, and minocycline, have been a mainstay of treatment for moderate-to-severe AV; however, their systemic side effects (including uncommon but severe minocycline-induced autoimmune reactions such as drug-induced lupus) warrant the need for alternative treatments.1Well D. Acne vulgaris: a review of causes and treatment options.Nurse Pract. 2013; 38: 22-31Crossref Scopus (30) Google Scholar, 2Kircik L.H. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications.J Drugs Dermatol. 2010; 9: 1407-1411PubMed Google Scholar, 3Smith K. Leyden J.J. Safety of doxycycline and minocycline: a systematic review.Clin Ther. 2005; 27: 1329-1342Abstract Full Text PDF PubMed Scopus (263) Google Scholar FMX-101, a new topical foam formulation of minocycline, was evaluated in a Phase 2, prospective, multicenter, randomized, double-blind, dose-finding study conducted in Tel-Aviv and Netanya, Israel. The objective of the study was to evaluate the safety, tolerability, and efficacy of 2 doses of FMX-101 (1% and 4%) versus vehicle in subjects with moderate-to-severe AV. Changes in lesion count at week 12 from baseline and Investigator Global Assessment (IGA) scores at week 12 were the co-primary endpoints. Of the 150 subjects screened and randomized (1:1:1) to FMX-101 4%, FMX-101 1%, or vehicle, 139 subjects (mean age, 16.5 years [range, 12.3-25]; 48% males) were dispensed study medications, attended at least one post-baseline visit, and were included in the modified intent-to-treat analysis. Subjects applied a small amount of foam (approximately 0.5 g) to the face once daily for 12 weeks and returned for 4 post-baseline visits at weeks 3, 6, 9 and 12, and had follow-up visit at 4 weeks after treatment. Demographic and baseline characteristics were similar across treatment groups. Treatment with FMX-101 4% led to a greater mean percentage reduction from baseline in lesion count versus vehicle at 12 weeks for both inflammatory (−71.7% vs −50.6%; P = .0001) and noninflammatory lesions (−72.7% vs −56.5%; P = .0197). The significant reduction in inflammatory lesions was observed as early as week 3 and persisted until the study end (Fig 1). With FMX-101 1%, significant reduction versus vehicle at week 12 occurred only for inflammatory lesions (−66.6% vs −50.6%; P = .0072). IGA score was significantly lower for FMX-101 4% versus vehicle from as early as week 6 (2 vs 2.5; P=.01) and persisted until week 12 (1.7 vs 2.4; P = .0001). Additionally, significantly more patients treated with FMX-101 4% versus vehicle achieved an IGA score of "clear" or "almost clear" (success criterion: IGA score <2) from week 9 until the study end (week 12: 53.2% vs 19.6%; P = .001) (Fig 2). More subjects treated with FMX-101 4% versus vehicle also had an IGA improvement of ≥2 grades at week 12 (36.2% vs 15.2%; P = .021). There was no significant difference in IGA improvement for FMX-101 1% versus vehicle. Treatment with FMX-101 was well tolerated and safe, with no drug-related systemic side effects or serious adverse events. Five reported adverse events were transient, mild in severity, and considered unrelated to the study medication. All adverse events resolved spontaneously by study end, except for a case of laryngitis, which was treated with medication. There were no significant differences in tolerability parameters between the FMX-101 and vehicle groups. Overall, these data suggest that FMX-101 may be an effective and well-tolerated treatment for moderate-to-severe AV. FMX-101 4% is the appropriate dose for further evaluation in phase 3 trials.