Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study
March 2018 | Volume 17 | Issue 3 | Case Reports | 333 | Copyright © March 2018
James J. Leyden MD,a Vilma Sniukiene MD,b David R. Berk MD,b and Alexandre Kaoukhov MDb
aPerelman Center for Advanced Medicine, Philadelphia, PA bAllergan plc, Irvine, CA
BACKGROUND: There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris.
METHODS: In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations.
RESULTS: Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred.
CONCLUSION: Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.
J Drugs Dermatol. 2018;17(3):333-338.
Oral tetracycline antibiotics, particularly doxycycline and minocycline, remain a standard component of care for moderate to severe inflammatory acne.1,2 However, doxycycline and minocycline have important limitations such as negative effects on various bacterial ecosystems, including the gastrointestinal tract.3 Additionally, their use may be limited by gastrointestinal side effects and photosensitivity with doxycycline, and vestibular effects with minocycline.2 Accordingly, new oral treatment options for moderate to severe acne are needed, particularly narrow spectrum antibiotics with favorable safety profiles.Sarecycline is a novel, once-daily, tetracycline-class, narrow spectrum antibiotic that was designed specifically for acne. In addition to demonstrating in-vitro anti-inflammatory effects (data on file, Allergan plc, Dublin, Ireland), sarecycline has potent activity against Gram-positive bacteria such as Propionibacterium acnes. Preclinical studies have demonstrated minimal inhibitory concentrations to inhibit 50% growth (MIC50) of P. acnes that are comparable to other tetracyclines used for acne. However, unlike doxycycline and minocycline, sarecycline demonstrates limited activity against enteric Gram-negative bacteria, including the commensal gut bacteria Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae (data on file, Allergan plc, Dublin, Ireland). Relative to other tetracyclines used for acne, sarecycline would be expected to cause less selective pressure on these enteric bacteria, resulting in less disruption of commensal organisms and less potential for inducing antibiotic resistance among them. Of note, multidrug-resistant Gram-negative infections are a growing public health concern, a major source of morbidity and mortality, and result in increased hospital and antibiotic healthcare expenditures.4 Additionally, results of a placebo-controlled, crossover, single-dose, phase 1, phototoxicity study suggest that sarecycline has low potential