By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved the first topical minocycline to treat moderate-to-severe acne vulgaris. The tetracycline class of antibiotics, and oral minocycline in particular, is considered first-line therapy in moderate-to-severe acne. Topical minocycline foam provides a therapeutic option without the systemic side effects of oral administration. The foam is distributed as Amzeeq.

INDICATIONS

Minocycline topical foam is indicated to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients ≥ 9 years of age.1

DOSAGE

The recommended dose is application to affected areas once daily.1 The foam should be applied at least one hour before bedtime, with instructions not to bathe, shower, or swim at least one hour after application. Minocycline is available as a 4% foam, with each gram containing 40 mg of micronized minocycline. It is available as a 30-g canister.

POTENTIAL ADVANTAGES

Following topical administration for 21 days, there was very low plasma minocycline concentration (maximum concentration of 1.1-1.5 ng/mL), more than 700 times lower than with oral administration.2 This could be associated with less development of bacterial resistance and disruption of gut microbiota.

POTENTIAL DISADVANTAGES

Minocycline foam is flammable.1 Flames and smoking should be avoided when applying and right after application. Exposure to natural and artificial sunlight should be limited.

COMMENTS

The safety and efficacy was assessed in three, 12-week, randomized, double-blind, vehicle-controlled studies involving 2,418 subjects with mainly moderate acne vulgaris (83-91%) and fewer with severe acne.1,3,4 At baseline, subjects scored 3 (moderate) or 4 (severe) on the Investigator Global Assessment (IGA). Also, mean inflammatory lesion counts were 31.2 and mean noninflammatory lesion counts were 49.1. The coprimary efficacy endpoints were the absolute change from baseline in inflammatory lesion counts and the proportion of subjects with treatment success at week 12. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear) and at least a two-grade improvement (decrease).

The absolute changes in inflammatory lesion counts for minocycline foam were -14.0, -13.7, and -16.4 compared to -11.2, -10.5, and -12.7 for the vehicle. This represented decreases of 44%, 43%, and 54% compared to decreases of 34%, 34%, and 42%, respectively, for the vehicle. A significant reduction of inflammatory lesion counts was observed at week 3 and maintained throughout the 12-week study. Treatment successes (compared to vehicle) for the three studies were (8.1% vs. 4.8%; 15.8% vs. 8.4%; and 30.8% vs. 19.6%). Study 1 did not achieve statistical significance for treatment success, and study 2 barely achieved statistical significance (P = 0.042).3 Minocycline foam also reduced noninflammatory lesion count compared to the vehicle.3,4 Generally, local adverse reactions were associated with the vehicle, including erythema, hyperpigmentation, dryness, and itching. The drug’s manufacturer recently reported on a different investigation that included subjects who completed a 12-week course in studies 1 and 2 as well as an additional 40 weeks of open-label treatment with minocycline foam (n = 291).5 The manufacturer reported that in this additional investigation, the treatment was well-tolerated, and effectiveness was maintained.

CLINICAL IMPLICATIONS

Guidelines from the American Academy of Dermatology recommend systemic antibiotics (e.g., doxycycline or minocycline) for the management of moderate-to-severe acne.6 Topical antibiotics in combination with benzoyl peroxide are recommended for mild acne, with clindamycin the preferred agent. Monotherapy is not recommended due to the risk of bacterial resistance. Minocycline foam is an appealing approach that significantly limits systemic exposure and its associated adverse reactions. While the drug is approved for moderate-to-severe acne, due to the relatively small number of study participants with severe acne, the effectiveness in this population needs to be established. In addition, long-term safety (e.g., bacterial resistance) and head-to-head comparison studies will be welcome. Minocycline foam is expected to be available this month at a cost of $582 per 30-g can.

REFERENCES

  1. Foamix Pharmaceuticals Ltd. Amzeeq Prescribing Information, October 2019. Available at: http://bit.ly/2PBsDoa.
  2. Jones TM, Ellman H, deVries T. Pharmacokinetic comparison of once-daily topical minocycline foam 4% vs oral minocycline for moderate-to-severe acne. J Drugs Dermatol 2017;16:1022-1028.
  3. Gold LS, Dhawan S, Weiss J, et al. A novel topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: Results of 2 randomized, double-blind, phase 3 studies. J Am Acad Dermatol 2019;80:168-177.
  4. Raoof TJ, Hooper D, Moore A, et al. Efficacy and safety of a novel topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: A phase 3 study. J Am Acad Dermatol 2019; Jun 1. pii: S0190-9622(19)30882-5. doi: 10.1016/j.jaad.2019.05.078. [Epub ahead of print].
  5. Foamix Pharmaceuticals. Foamix announces publication of Amzeeq (minocycline) topical foam long-term safety data for treatment up to 1 year in Journal of Clinical and Aesthetic Dermatology, Nov. 4, 2019. Available at: http://bit.ly/2PHjI4V.
  6. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-973.e33.