ABSTRACT: Background and objectives: Acne vulgaris is a highly prevalent and multifactorial skin disorder that can adversely impact health-related quality of life. Factors that contribute to the pathogenesis of acne include pilosebaceous proliferation of proinflammatory Propionibacterium acnes (P. acnes) bacteria, presence of circulating androgens, excess sebum production, abnormal follicular keratinization, and multiple inflammatory cascades. Oral tetracyclines-especially doxycycline and minocycline-are frequently prescribed for the treatment of moderate-to-severe acne, given their anti-inflammatory properties and their effect on P. acnes reduction. Notwithstanding their established efficacy in the management of acne vulgaris, there is a desire to limit systemic exposure to antibiotics given growing concerns regarding bacterial resistance as well as the potential for serious side effects. This report describes outcomes of two randomized, vehicle-controlled trials (Phases IIa and IIb) of BPX-01, a topical minocycline gel, in the treatment of moderate-to-severe acne. Methods: In Study 1 (NCT02709096), at a single center, 33 subjects with highly fluorescing facial skin were randomized 2:1 to BPX-01 1% or vehicle control once-daily treatment for four weeks. Changes in P. acnes quantitative bacteriological cultures were assessed, as well as cutaneous tolerance to the study drug by both subjects and the investigator. In Study 2 (NCT02815332), subjects with moderate-to-severe inflammatory nonnodular acne (n=226) at 15 centers were randomized 1:1:1 to treatment with BPX-01 1%, BPX-01 2%, or vehicle control once-daily for 12 weeks. The primary endpoint was reduction in the number of inflammatory lesions; other endpoints included the number of noninflammatory lesions, Investigator's Global Assessment (IGA) of severity, and subjective ratings (investigator and subject) of acne. In both studies, cutaneous tolerability and safety were assessed, and plasma minocycline levels were tracked with a highly sensitive assay. Results: In Study 1, BPX-01 treatment reduced P. acnes colonization by 90.9 percent, which exceeded the reduction in the vehicle control group (65.53%; p=0.020). In Study 2, treatment with BPX-01 2% reduced the number of inflammatory lesions by 58.5 percent, exceeding the reduction in the vehicle control group (43.8%; p=0.0256). Trends toward an improvement preferential to BPX-01 2% were observed in the other endpoints. Across both studies, BPX-01 treatment was well-tolerated, with no photosensitivity, postinflammatory hyperpigmentation, or skin discoloration reported. A single subject (out of 259 study participants ) was identified to have detectable levels of plasma minocycline at low levels (42ng/mL) after 12 weeks of treatment but had no signs or symptoms associated with systemic administration of minocycline. Conclusion: BPX-01 appears to exhibit an effectiveness profile for reduction of inflammatory (nonnodular) acne lesions similar to that of oral minocycline formulations. However, because BPX-01 is topical and exhibits negligible systemic exposure, the likelihood of adverse events associated with oral minocycline use is much lower. These results demonstrate effectiveness of BPX-01 topical minocycline gel in reducing P. acnes colonization, suggesting that the BPX-01 2% formulation is a promising treatment for moderate-to-severe nonnodular, inflammatory acne vulgaris in both reduction of inflammatory lesions and also overall improvement in facial acne according to IGA.
