contraceptives (COCs) for moderate to severe acne.9 Lastly, oral isotretinoin is optimal treatment when truncal acne is severe and refractory to other therapies and associated with marked scarring.9
Sarecycline is a narrow-spectrum, 3rd generation, oral tetracycline-class antibiotic and the first new FDA-approved antibiotic specifically developed for acne treatment in approximately 5 decades.10 Unlike other tetracyclines, sarecycline has a stable modification at the C7 hydrocarbon ring position that allows for direct interaction with the A site codon on messenger RNA (mRNA).11,12 Structural modifications unique to sarecycline support its designation as a narrow-spectrum antibiotic, exhibiting high activity against Cutibacterium acnes, staphylococci, and streptococci, coupled with negligible activity against Gram-negative bacteria and several anaerobic organisms.11-13 In addition to antibiotic activity, sarecycline has shown additional characteristics relevant to acne treatment, including anti-inflammatory properties.13 Pivotal phase-3 studies demonstrate that sarecycline is safe, well-tolerated, and effective for moderate to severe facial acne, with low rates of adverse events (AEs) that are commonly associated with broad-spectrum tetracyclines, including “pill esophagitis”/ abdominal pain, phototoxicity, vertigo, vaginal candidiasis, and hyperpigmentation.14 Within these phase 3 studies, efficacy for truncal acne was captured in affected subjects based on IGA assessments. This article reports the efficacy of weight-based dosing of sarecycline (1.5 mg/kg/day) administered once daily for 12 weeks in this patient population.
Sarecycline is a narrow-spectrum, 3rd generation, oral tetracycline-class antibiotic and the first new FDA-approved antibiotic specifically developed for acne treatment in approximately 5 decades.10 Unlike other tetracyclines, sarecycline has a stable modification at the C7 hydrocarbon ring position that allows for direct interaction with the A site codon on messenger RNA (mRNA).11,12 Structural modifications unique to sarecycline support its designation as a narrow-spectrum antibiotic, exhibiting high activity against Cutibacterium acnes, staphylococci, and streptococci, coupled with negligible activity against Gram-negative bacteria and several anaerobic organisms.11-13 In addition to antibiotic activity, sarecycline has shown additional characteristics relevant to acne treatment, including anti-inflammatory properties.13 Pivotal phase-3 studies demonstrate that sarecycline is safe, well-tolerated, and effective for moderate to severe facial acne, with low rates of adverse events (AEs) that are commonly associated with broad-spectrum tetracyclines, including “pill esophagitis”/ abdominal pain, phototoxicity, vertigo, vaginal candidiasis, and hyperpigmentation.14 Within these phase 3 studies, efficacy for truncal acne was captured in affected subjects based on IGA assessments. This article reports the efficacy of weight-based dosing of sarecycline (1.5 mg/kg/day) administered once daily for 12 weeks in this patient population.
MATERIALS AND METHODS
Study Design
Two identically designed, randomized, double-blind, placebocontrolled, parallel-group, phase 3 studies in patients 9 years of age and older were conducted in the United States at multiple study centers.10,14 Each study included a 35-day screening period followed by a 12-week treatment period (Figure 1). During the treatment period, patients were randomized 1:1 to receive daily oral doses of either 1.5 mg/kg sarecycline tablets or placebo tablets. Patients returned to the clinic following 3, 6, 9, and 12 weeks of treatment to determine Investigator’s Global Assessment (IGA) scores. IGA scores for chest and back were reported as exploratory efficacy endpoints in both phase 3 studies. In the current analysis, pooled treatment efficacy was evaluated in truncal acne based on IGA scores of the chest and back following 3, 6, 9, and 12 weeks of treatment.
Enrollment Criteria
Eligibility criteria for the intent-to-treat (ITT) population in the phase 3 studies included patients who were 9 to 45 years, weighed between 33–136 kg, and had facial acne vulgaris with 20–50 inflammatory lesions (papules, pustules, and nodules), up to 100 non-inflammatory lesions (open and closed comedones), no more than 2 nodules, and an IGA score of moderate (IGA 3) or severe (IGA 4) at baseline.14 In the current analysis, patients who met the eligibility criteria in the pivotal phase 3 studies and with an IGA score ≥2 at baseline for chest or back acne were pooled and analyzed for study outcomes. Lesion count assessments were not used to evaluate therapeutic outcomes with truncal acne in these pivotal trials as evaluation of facial acne response was the primary objective.14
Patients were excluded from the phase 3 studies if they had any dermatological condition of the face that could interfere with clinical evaluations, any chronic illness interfering with study evaluations, allergy/hypersensitivity or resistance to tetracyclines, or drug-induced acne; designated washout periods were mandated for topical acne therapies, hormonal contraceptive use, systemic retinoids, systemic corticosteroids, androgens, or anti-androgens.14
Endpoints
Percentage of patients with IGA success, defined as ≥2-point decrease (improvement) in IGA score from baseline (IGA score ≥2) and a score of clear/almost clear, was evaluated for both the chest and back.14
Statistical Analyses
The treatment difference between sarecycline and placebo in the proportion of patients who achieved IGA success was analyzed using the Cochran-Mantel-Haenszel (CMH) test with integrated data from SC1401 and SC1402.14 Pooled analysis for both studies were considered statistically significant if P<0.05 and when the corresponding analysis for both individual studies also achieved statistical significance.
RESULTS
Patient Demographics and Baseline Characteristics (Truncal Acne Population)
Of 2002 total patients, 839 patients with chest acne and 1134
Of 2002 total patients, 839 patients with chest acne and 1134
