not be applicable to prescription medications such as FMX101 and BPX-01. However, both products were found to have approximately 800-times less systemic absorption than oral minocycline.
In regards to reference number 35, this citation refers to the average plasma concentration produced with a single dose of oral minocycline (758 ng/ml). Placing the citation lower down in the paragraph may have provided more specificity regarding the reference.
In response to the mention of a two-period, crossover study of FMX101 and oral minocycline, we chose to discuss the phase II trial of BPX-01 because it tested a single-use 1g application of the topical drug for the purpose of comparing a single 100mg dose of oral minocycline. The FMX101 study referenced by the letter’s author was a maximal use trial (MUSE) for safety, which was deemed less relevant for comparing systemic exposure with a single dose application. BPX-01 has not yet conducted a MUSE trial for head-to-head comparison with FMX101.
In response to queries about the action of ethanol in BPX-01, ethanol is a well-known solvent that is miscible with lipids and possesses a rapid evaporative quality. We acknowledge this paradox might raise questions about its usefulness in acne treatment. The statements regarding ethanol’s ability to penetrate the pilosebaceous unit and exert antimicrobial action against P. acnes was taken from the 2018 research presentation of Del Rosso JQ et al, entitled, “The benefits of ethanol in a drug delivery vehicle for topical acne treatment.” This is cited in our reference section. Del Rosso’s work made reference to “the solvent distribution coefficient properties of ethanol that enable it to penetrate and enhance the penetration of other dissolved molecules into the skin.”1,2 Further evidence regarding the use of ethanol in BPX-01 as the major excipient was seen in their phase IIa and IIb trials, where the vehicle arm showed a 65.3% reduction in P. acnes and a 43.8% reduction of inflammatory lesions at week 12, respectively.3 These benefits cannot be linked directly to ethanol however, as the vehicle contained other excipients or components.
To our knowledge no studies have been published evaluating the long-term impact of ethanol on the skin, although many prescription and over-the-counter products utilize ethanol without worrisome long-term sequelae, including hand sanitizers and facial toners.
In regards to non-inflammatory acne, we chose not to discuss the effects of either formulation on comedonal acne. This is because FMX101 and BPX-01 trials have been focused on moderate to severe inflammatory acne as a primary endpoint. Of note, absolute change in non-inflammatory lesion count at week-12 was a secondary endpoint in the FMX101 phase III numbers 22, 04, and 05 trials and showed statistically significant reductions. Change in non-inflammatory lesion count was an exploratory endpoint in the BPX-01 phase IIb trial. We would welcome any additional information regarding either product’s intention of studying comedonal acne as a primary endpoint.
We sincerely hope this response addresses the questions and concerns of the response letter author. We are encouraged by the progress made in both formulations of topical minocycline and applaud both company’s efforts to reduce antibiotic resistance while effectively treating such a ubiquitous condition.
Lauren Meshkov Bonati MD
and Jeffrey S. Dover MD FRCPC
References:
In regards to reference number 35, this citation refers to the average plasma concentration produced with a single dose of oral minocycline (758 ng/ml). Placing the citation lower down in the paragraph may have provided more specificity regarding the reference.
In response to the mention of a two-period, crossover study of FMX101 and oral minocycline, we chose to discuss the phase II trial of BPX-01 because it tested a single-use 1g application of the topical drug for the purpose of comparing a single 100mg dose of oral minocycline. The FMX101 study referenced by the letter’s author was a maximal use trial (MUSE) for safety, which was deemed less relevant for comparing systemic exposure with a single dose application. BPX-01 has not yet conducted a MUSE trial for head-to-head comparison with FMX101.
In response to queries about the action of ethanol in BPX-01, ethanol is a well-known solvent that is miscible with lipids and possesses a rapid evaporative quality. We acknowledge this paradox might raise questions about its usefulness in acne treatment. The statements regarding ethanol’s ability to penetrate the pilosebaceous unit and exert antimicrobial action against P. acnes was taken from the 2018 research presentation of Del Rosso JQ et al, entitled, “The benefits of ethanol in a drug delivery vehicle for topical acne treatment.” This is cited in our reference section. Del Rosso’s work made reference to “the solvent distribution coefficient properties of ethanol that enable it to penetrate and enhance the penetration of other dissolved molecules into the skin.”1,2 Further evidence regarding the use of ethanol in BPX-01 as the major excipient was seen in their phase IIa and IIb trials, where the vehicle arm showed a 65.3% reduction in P. acnes and a 43.8% reduction of inflammatory lesions at week 12, respectively.3 These benefits cannot be linked directly to ethanol however, as the vehicle contained other excipients or components.
To our knowledge no studies have been published evaluating the long-term impact of ethanol on the skin, although many prescription and over-the-counter products utilize ethanol without worrisome long-term sequelae, including hand sanitizers and facial toners.
In regards to non-inflammatory acne, we chose not to discuss the effects of either formulation on comedonal acne. This is because FMX101 and BPX-01 trials have been focused on moderate to severe inflammatory acne as a primary endpoint. Of note, absolute change in non-inflammatory lesion count at week-12 was a secondary endpoint in the FMX101 phase III numbers 22, 04, and 05 trials and showed statistically significant reductions. Change in non-inflammatory lesion count was an exploratory endpoint in the BPX-01 phase IIb trial. We would welcome any additional information regarding either product’s intention of studying comedonal acne as a primary endpoint.
We sincerely hope this response addresses the questions and concerns of the response letter author. We are encouraged by the progress made in both formulations of topical minocycline and applaud both company’s efforts to reduce antibiotic resistance while effectively treating such a ubiquitous condition.
Lauren Meshkov Bonati MD
and Jeffrey S. Dover MD FRCPC
References:
- Scheuplein RJ, Blank IH. Mechanism of percutaneous absorption IV. Penetration of nonelectrolytes from aqueous solution and from pure liquids. J Invest Dermatol. 1973;60(5):286-96.
- Lachenmeier DW. Safety and evaluation of topical application of ethanol on the skin and inside the oral cavity. J Occup Med Toxicol. 2008;13(3):26.
- Alexis A, Del Rosso JQ, et al. BPX-01 Minocycline topical gel shows promise for the treatment of moderate-to-severe inflammatory acne vulgaris. J Clin Aesthet Dermatol. 2018;11(11):25-35. Epub 2018 Nov 1.
