FC20 Poster Kirsch CL108 = Brandon Kirsch, MD1, Janet DuBois, MD2, Martin N. Zaiac3, Sanjeev Ahuja, MD, MBA, FACP4, Deepak Chadha, MS, MBA, RAC5 1Kirsch Dermatology, Naples, FL, 2DermResearch Inc., Austin, TX, 3Sweet Hope Research Specialty, Hialeah, FL , 4Former CMO, Brickell Biotech, Inc., Boulder, CO, 5Brickell Biotech, Inc., Boulder, CO A Multi-Center, Open-Label Extension Study to Assess the Long-Term Safety, Tolerability and Pharmacokinetics, and Explore the Efficacy of Sofpironium Bromide Gel, 15% Applied Topically to Children and Adolescents, 9 to 16 Years of Age, with Primary Axillary Hyperhidrosis (BBI-4000-CL-108) Hyperhidrosis affects approximately 15 million Americans. Sofpironium bromide is a retro- metabolically designed analog of glycopyrrolate (anticholinergic) in development for the topical treatment of primary axillary hyperhidrosis. Retro-metabolically designed drugs are intended to be rapidly metabolized in the bloodstream, potentially allowing for optimal therapeutic effect at the site of application with minimal systemic side effects. Approximately 2.1% of individuals <18 years of age have primary hyperhidrosis with ~65% having axillary hyperhidrosis.1 The long-term safety, tolerability and efficacy of topical treatments for axillary hyperhidrosis have rarely been studied in the pediatric population. The mean age (SD) of the subjects was 13.3 (2.29) years. Sixteen subjects completed 24-weeks of treatment. Seven subjects had treatment emergent adverse events (TEAEs). Four subjects had TEAEs that were considered related to study drug, which included expected systemic anticholinergic effects (blurred vision, dry mouth, dry eyes, mydriasis) and local site reactions (pain, pruritus, rash, erythema). Two subjects discontinued the study due to adverse events, which included dry eye, dry mouth, pruritus and rash. The majority of subjects did not have any local signs or symptoms and none were severe. Pharmacokinetic analysis did not show any evidence of sofpironium or BBI-4010 (major metabolite) accumulation, with most subjects having plasma concentrations that were not quantifiable. For the validated patient-reported outcome measure Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax), the mean (SD) change from baseline (from study BBI-4000-CL-105) to Week 24 of this study was -1.91 (1.038). A change of -1.00 represents clinically meaningful improvement. In this 24-week study in the pediatric population, sofpironium bromide gel, 15% appeared safe and generally well tolerated. The majority of subjects did not report any TEAEs, and there were no severe or serious AEs. There was no evidence of drug accumulation. There was clinically meaningful improvement in axillary hyperhidrosis. Brickell Biotech, Inc. supported the study and preparation of this abstract. Funding Statement Conclusion Background Methods Academic Poster Presented at the 2020 Fall Clinical Dermatology Conference | Las Vegas, NV | October 29 - November 1, 2020 Objective Evaluate the long-term safety, tolerability and pharmacokinetics of topically applied sofpironium bromide gel, 15% for the treatment of axillary hyperhidrosis in pediatric subjects, as well as to explore efficacy. Figure 1: Sofpironium and BBI-4010 Plasma Concentration Levels Table 1: Incidence & Severity of TEAEs (n=21) Results Twenty-one subjects with primary axillary hyperhidrosis of ≥6 months duration ranging in age from 9 to 16 years, who had participated in and completed a previous 1-week safety and pharmacokinetic (PK) study (BBI-4000-CL-105), were enrolled and treated with sofpironium bromide gel, 15% applied to the axillae for 24 weeks. 1Doolittle J, Walker P, Mills T, Thurston J. Hyperhidrosis; an update on prevalence and severity in the United States. Arch Dermatol Res. 2016; 308:743-749. References 0 0. 1 0. 2 0. 3 Wee k 0 Wee k 4 Wee k 24C o n ce n tr a ti o n ( n g /m L) Nominal Timepoint So fp iro niu m B BI -40 10 PK Study (BBI-4000-CL-105) Day 8 (± 1 day)/Visit 4 Day 28 (±3)/ Visit 2 Week 26/ End of Study Day 1/ Visit 1 1 pump (~0.67mL) applied to each axilla, once daily, before bedtime Day 56 (±5)/ Visit 3 Day 84 (±5)/ Visit 4 Day 112 (±5)/ Visit 5 Day 140 (±5)/ Visit 6 Day 168 (±5)/ Visit 7 Day 182 (±5)/ Visit 8 Week 4 Week 8 Week 12 Week 16 Week 20 Week 24/ End of Treatment or Early Termination Week 0 Screening/Enrollment PK sample ≥12 hours after last dose PK sample ≥12 hours after last dose Subjects with TEAEs 7 (33.3%) Number of TEAEs 21 Subjects with Treatment-Related AEs 4 (19.0%) Subjects with SAEs 0 Subject Discontinuations Due to TEAE 2 (9.5%) TEAE by Severity (all TEAEs) Mild 5 (23.8%) [8] Moderate 5 (23.8%) [13] TEAE by Severity (relationship – possibly, probably or definitely related) Mild 3 (14.3%) [4] Moderate 4 (19.0%) [11] Table 2: Frequency of Anticholinergic TEAEs (≥5%) (n=21) Dry Eye 1 (4.8%) [1] Dry Mouth 1 (4.8%) [1] Mydriasis 1 (4.8%) [1] Vision Blurred 1 (4.8%) [1] Note: A TEAE is defined as any AE occurring on or after first dose. The first number corresponds to the count of unique subjects and percentage, while the second number in [n] is the count of raw events. Subjects are counted only once at the strongest relationship to the study medication. 0 1 2 3 4 B aselin e Wee k 24 H D S M -A x S co re Study Timepoint The Hyperhidrosis Disease Severity Measure-Axillary© (HDSM-Ax) is a validated 11-item measure of axillary hyperhidrosis severity and frequency with a 5-point scale for each item. A change of -1.00 from the mean baseline score has been defined to represent clinically meaningful improvement. Figure 2: Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Scores Figure 3: Patient Global Assessment of Severity (PGI-S) 0 2 4 6 8 10 Ve ry S e ve re S e ve re M oder ate M i ld Non eN u m b e r o f S u b je ct s Severity B aselin e Wee k 24 0 2 4 6 8 10 V e ry Mu ch W o r se M od er ate ly W o r se A Lit tle W or se A Lit tle Be tt e r M od er ate ly B e tt e r V e ry Mu ch B et te rN u m b e r o f S u b je ct s Change Wee k 12 Wee k 24 PGI-C: The response that best describes the overall change in underarm sweating since the subject started taking the study medication. Patient Global Impression of Severity (PGI-S): The response that best describes the severity of underarm sweating over the past week. Figure 4: Change in Global Assessment of Severity (PGI-C) Any Present Minimal Mild Moderate Severe Subjects with any Local Symptoms by Worst Severity 10 (47.6%) 4 (19.0%) 1 (4.8%) 5 (23.8%) 0 Burning 4 (19.0%) 1 (4.8%) 1 (4.8%) 2 (9.5%) 0 Stinging 3 (14.3%) 1 (4.8%) 1 (4.8%) 1 (4.8%) 0 Itching 7 (33.3%) 2 (9.5%) 2 (9.5%) 3 (14.3%) 0 Scaling 1 (4.8%) 1 (4.8%) 0 0 0 Erythema 9 (42.9%) 4 (19.0%) 2 (9.5%) 3 (14.3%) 0 Note: The severity shown is the greatest severity reported for a particular assessment (burning/stinging/itching/scaling/erythema). Maximum severity assessed for either axilla is reported. Table 3: Local Site Reactions (n=21)