PowerPoint Presentation David M. Pariser1, Lawrence J. Green2, Edward L. Lain3, Jodi L. Johnson4, Ayman Grada5 1Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA, USA; 2George Washington University School of Medicine, Washington, DC, USA; 3Austin Institute for Clinical Research, Pflugerville, TX, USA; 4Departments of Dermatology and Pathology, Feinberg School of Medicine, Northwestern University, USA, 5R&D and Medical Affairs, Almirall (US), Exton, Pennsylvania, USA. Email: Grada@bu.edu Introduction Methods Results Conclusion Long-term Safety and Tolerability of Sarecycline for the Treatment of Acne Vulgaris: Results from a Phase III, Multicenter, Open-Label Study and a Phase I Phototoxicity Study  Sarecycline is a narrow-spectrum tetracycline-class antibiotic designed for the treatment of moderate-to-severe acne.  Sarecycline’s narrow-spectrum anti-bacterial activity and lipophilicity may minimize side effects commonly associated with broad-spectrum tetracyclines, such as minocycline and doxycycline.  Here, we report the results of 2 identically designed, phase 3 pivotal trials, SC1401 and SC1402, to evaluate the efficacy and safety of once- daily sarecycline (n=2002). • Sarecycline was associated with low rates of TEAEs, with nasopharyngitis, upper-respiratory-tract infection, headache, and nausea being the only TEAEs reported ≥2% or more of patients with moderate-to-severe acne vulgaris aged nine years or older treated with sarecycline once daily for up to 40 weeks. • Rates of TEAEs commonly associated with other tetracycline antibiotics were for dizziness (0.4%) and sunburn (0.2%), and for gastrointestinal TEAEs, nausea (2.1%), vomiting (1.9%), and diarrhea (1.0%). Vulvovaginal mycotic infection (0.8%). • Sarecycline has low potential to cause clinically significant phototoxicity • No clinically meaningful safety findings were noted.  Patients (n=483) aged 9 years or older with moderate-to-severe acne who completed one of two prior pivotal Phase III, double-blind, placebo-controlled, 12- week trials in which they received sarecycline 1.5mg/kg/day or placebo once daily were continued on once daily sarecycline for up to 40 weeks Study visits: weeks 2, 6, 12,18, 24, 32 and 40  Excluded: Receiving/planning to receive any systemic acne vulgaris medication, systemic retinoids, systemic corticosteroids or any androgen/anti-androgenic therapy (e.g. testosterone, spironolactone)  Included: Allowed use of topical acne vulgaris medications  The primary assessment was the safety of sarecycline 1.5mg/kg/day for 40 weeks as indicated by adverse events (AEs), vital signs, electrocardiograms, clinical laboratory tests, and physical examinations.  Patterns of sarecycline use were a secondary assessment.  Subjects treated until adequate improvement obtained as per Investigator judgment (eg, IGA score of 0 or 1) and re-initiated if acne recurred (eg, IGA score ≥ 3) Phase-3 Long-term Safety (40-week) Synopsis Pariser DM, Green LJ, Lain EL, Schmitz C, Chinigo AS, McNamee B, Berk DR. Safety and Tolerability of Sarecycline for the Treatment of Acne Vulgaris: Results from a Phase III, Multicenter, Open-Label Study and a Phase I Phototoxicity Study. The Journal of Clinical and Aesthetic Dermatology. 2019 Nov;12(11):E53.  19 Subjects (healthy; non-smoker, men, aged 18 to 45 years) received placebo or 240mg of sarecycline in a random order in each of the two treatment periods (not weight based)  A two-treatment, two-period, two-sequence crossover design. Treatment periods were separated by at least nine days  At three hours after administration of the study treatment, a previously unexposed area of each subject’s back was irradiated with 16J/cm2 of UVA, after which point, another area was irradiated with UVA/UVB at 50 percent of the subject’s minimum erythemal dose (MED)  UV-exposed skin was assessed visually at 24, 48, and 72 hours after irradiation, and UV-induced skin reaction was evaluated using dermal response score scale  Mean and maximum numerical UV-induced dermal response scores were determined for sarecycline and placebo Phase-1 Phototoxicity TEAEs of Interest Safety Population Placebo/Sarecycline (N=236), n (%) Sarecycline/Sarecycline (N=247), n (%) Total (N=483), n (%) Common TEAEs (≥2% of patients in either group) Nasopharyngitis 13 (5.5) 5 (2.0) 18 (3.7) Upper-respiratory-tract infection 7 (3.0) 9 (3.6) 16 (3.3) Headache 9 (3.8) 5 (2.0)b 14 (2.9)b Urinary tract infection 2 (0.8) 5 (2.0) 7 (1.4) Gastrointestinal Nausea 4(1.7) 6(2.4) 10(2.1) Vomiting 3(1.3) 6(2.4) 9(1.9) Diarrhea 3 (1.3) 2 (0.8) 5 (1.0) Constipation 2 (0.8) 0 2 (0.4) Vestibular Dizziness 1(0.4) 1(0.4) 2(0.4) Vertigo 0 0 0 Tinnitus 0 0 0 Sunburn and skin hyperpigmentation Sunburn 0 1(0.4) 1(0.2) Skin hyperpigmentation 1(0.4) 0 1(0.2) Vaginal yeast infections in females Vulvovaginal mycotic infection 0 2(1.6) 2(0.8) Genital fungal infection 0 1(0.4) 1(0.2) Genital candidiasis 1(0.4) 0 1(0.2) Results: Dermal response to UV exposure did not exceed mild erythema with either sarecycline or placebo at any time point, and the mean and maximum UV- induced dermal response scores for both sarecycline and placebo were low. No TEAEs or serious AEs were reported in the phototoxicity study The safety population included 483 patients; 354 patients (73.3%) completed the study 1 mailto:Grada@bu.edu https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937166/ Slide Number 1