Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials.

Background: Side effects may limit the use of current tetracycline-class antibiotics for acne. Objective: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne. Methods: Patients 9-45 years with moderate to severe facial acne (Investigator's Global Assessment [IGA] score >= 3 20-50 inflammatory and <= 100 noninflammatory lesions, and <= 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402). Results: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P<0.0001 and P=0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean I percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of 51.8% and 49.9% (sarecycline), respectively, versus 35.1% and 35.4% (placebo; P<0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P<0.05) and week 9 in SC1402 (P<0.01). In SC1401, the most common TEAEs (in >= 2% of either sarecycline placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1 %; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1 %; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in <= 1% of sarecycline patients. Gastrointestinal TEAS rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low. Conclusion: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics.