Treating Acne With Topical Antibiotics

August 2019 | Volume 18 | Issue 8 | Editorials | 837 | Copyright © August 2019

Dr. Iain A. Stuart

Chief Scientific Officer Foamix Pharmaceuticals

phase 2b study for BPX-01 2% was not statistically different from vehicle at week 12. On the contrary, there were statistically significant reductions in non-inflammatory lesion counts at the same timepoint in all phase 3 studies evaluating FMX101. Dr. Iain A. Stuart Chief Scientific Officer Foamix Pharmaceuticals

References:
  1. Bonati LD and Dover JS. Treating acne with topical antibiotics: current obstacles and the introduction of topical minocycline as a new treatment option. J Drugs Dermatol. 2019;18(3):240.
  2. Alexis A, Del Rosso JQ, Desai SR, Downie JB, Draelos, ZD, Feser C, Forconi R, Fowler JF, Gold M, Kaufman-Janette J, Lain E, Lee M, Ling M, Shamban T, Werschler P and Daniels A-M. BPX-01 minocycline topical gel shows promise for the treatment of moderate-to-severe inflammatory acne vulgaris. J Clin Aesthet Dermatol. 2018;11(11):25. 
  3. Stein Gold L, Dhawan S, Weiss J, Draelos Z, Ellman Hand Stuart IA. 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(1):168-177. 
  4. Raoof J, Hooper D, Moore A, Zaiac M, Sullivan T, Kircik L, Lain E, Jankicevic J and Stuart I. FMX101 4% topical minocycline foam foe the treatment of moderate to severe acne vulgaris: efficacy and safety from a phase 3, randomized, double-blind, vehicle-controlled study. Poster presentation, October 2018, Fall Clinical Dermatology Conference 2018.
  5. Kircik LH. Not all foams are created equal: vehicle characteristics can affect patient outcomes. J Drugs Dermatol. 2019. Volume 18(2):s98
  6. Maximal Usage Trials for Topical Active Ingredients Being Considered for Inclusion in an Over-The-Counter Monograph: Study Elements and Considerations Guidance for Industry, FDA draft guidance, May 2018, Section 11
  7. Jones TM, Ellman Hand De Vries T. Pharmacokinetic comparison of once-daily topical minocycline foam 4% vs oral minocycline for moderate-to-severe acne. J Drugs Dermatol. 2017; 16(10):1022.
  8. Clintrials.gov records accessed 22MAR19: https://clinicaltrials.gov/ct2/show/NCT028 l 5332?cond=BPX-0 1 &rank=2; https://clinicaltrials.gov /ct2/ show /NCT02 709096? cond= BPX-01 &rank= 1
Response

Dear Editor,

Our primary goal was to submit a non-biased article reviewing two topical minocycline formulations that purport to treat acne while reducing antibiotic resistance. Statements made regarding each formulation were based on the most current available data at the time of submission. The article describes data from pre-clinical and clinical trials of each formulation, respectively, but no head-to-head studies have been performed. Comparisons between the two products should be done with caution due to varying stages of research and preliminary formulations that may not represent finalized products. We would like to re-emphasize that both investigational drugs hold promise for effectively treating acne, reducing systemic antibiotic exposure, and ideally lowering rates of antibiotic resistance.

In response to queries about Table 2, we would like to clarify that IGA results in neither the BPX-01 phase 2 study or the FMX101 study 04 showed statistical significance. This is not unexpected, as the studies were likely powered for a different primary endpoint, the change in inflammatory lesions from baseline at week 12. Vehicle composition was presented in this table to clarify which formulations were tested during clinical trials. Final formulations and vehicles may differ.

In response to queries about Table 3, readers should be reminded that MNC-L 4% was a non-foam, lipophilic formulation of topical minocycline that should not be considered an early version of FMX101. As described in the text and table footnotes, MNC-L 4% was designed solely for the purposes of testing lipophilic versus hydrophilic penetrance.

Figure 3 is a presentation of inflammatory lesion counts from the most recent phase II BPX-01 clinical trial and from an oral minocycline phase III trial. Unfortunately, the FMX101 trial data was not included due to a different visit and assessment schedule (3, 6, 9, and 12-weeks) than that of BPX-01 and the oral minocycline trial, which had the same visit and assessment schedule (2, 4, 6, 8, and 12-weeks).
As a result, conclusions cannot be made about time to improvement between BPX-01 and FMX101 from this data set. The statement, “BPX-01 trials reported a quicker reduction than FMX101 in its respective trial” was unintentionally misleading given the differing 2-week versus 3-week timepoints.

In response to the concern of our use of the term “undetectable” rather than “unquantifiable” minocycline levels, we would like to clarify that “undetectable” does not imply a zero-level of minocycline in the plasma, but rather, a level so low it cannot be detected by the assay. A more appropriate term may have been “unquantifiable.” It should also be mentioned that the 10ng/ml LLOQ mentioned in the letter to the editor was taken from the FDA draft guidelines on maximal use study parameters for OTC products. This LLOQ may