ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics; Ortho Dermatologics is a division of Bausch Health US, LLC • Presented at Fall Clinical 2020 • October 29 - November 1, 2020 • Virtual Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race Fran E Cook-Bolden, MD1; Neal Bhatia, MD2; Jonathan S Weiss, MD3; Neil Sadick, MD4; Stephen K Tyring, MD, PhD5; Eric Guenin, PharmD, PhD, MPH6; Anya Loncaric, MS7; Susan Harris, MS8 1Fran E. Cook-Bolden, MD, PLLC and Department of Dermatology, Mount Sinai Hospital Center, New York, NY; 2Therapeutics Clinical Research, San Diego, CA; 3Georgia Dermatology Partners, and Gwinnett Clinical Research Center, Inc., Snellville, GA; 4Department of Dermatology, Weill Cornell Medical College, New York, NY and Sadick Dermatology, New York, NY; 5University of Texas Health Science Center, Houston, TX; 6Ortho Dermatologics,* Bridgewater, NJ; 7Bausch Health US, LLC,* Petaluma, CA; 8Bausch Health US, LLC,* Bridgewater, NJ *Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC. SYNOPSIS ■ Patients with skin of color have an increased risk of acne and inflammation-related sequalae, including post-inflammatory hyperpigmentation (PIH) associated with acne resolution or irritation from treatment1 ■ Topical retinoids such as tazarotene treat acne by inhibiting multiple inflammatory pathways and normalizing desquamation2; however, skin irritation and other skin reactions may limit the use of some tazarotene gel and cream formulations3 ■ A recently-approved, lower-dose tazarotene 0.045% lotion formulation (Arazlo™, Ortho Dermatologics) was developed utilizing polymeric emulsion technology (Figure 1)4 • This highly spreadable lotion formulation was developed to allow for more efficient delivery of tazarotene into dermal layers while reducing the potential for skin irritation4 FIGURE 1. Polymeric Emulsion Technology for Tazarotene 0.045% Lotion 3-D mesh (polymeric matrix) holding water and water-soluble hydrating agents within the mesh Droplets consisting of tazarotene and oil-soluble moisturizing agents held apart by the 3-D mesh 3-D mesh allows for uniform distribution of tazarotene and moisturizing agents 25-50 μm 1-2 μm OBJECTIVE ■ Data from two phase 3 studies were pooled to evaluate the efficacy and safety of once-daily tazarotene 0.045% lotion compared with vehicle lotion in participants of White or Black race (self-identified) METHODS ■ In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321),5,6 participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1614) • In these studies, CeraVe® hydrating cleanser and CeraVe® moisturizing lotion (L’Oreal, NY) were provided as needed for optimal moisturization/cleaning of the skin. ■ This pooled, post hoc analysis included subsets of participants segmented by White (n=1191) or Black race (n=262) ■ Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success; treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also evaluated RESULTS FIGURE 2. Participant Demographics and Baseline Characteristics (ITT Population, Pooled) Black (n=262) White (n=1191) 24.0 years 19.6 years 26.6 28.5 40.6 40.9 Mean age: % female: % Non-Hispanic/Latino: Mean in�ammatory lesion count: Mean nonin�ammatory lesion count: % EGSS distribution (moderate and severe): 63.2%78.2% 74.2%94.3% 90% 10% 95% 5% • Demographics and baseline characteristics were generally similar between subgroups, though: • Black participants were on average older and more likely to be female • A higher proportion of White participants had a baseline EGSS of 4 (“severe”) EGSS, Evaluator’s Global Severity Score; ITT, intent to treat. FIGURE 3. Efficacy Outcomes at Week 12 by Race (ITT Population, Pooled) -70% -50% -30% -10% Black Participants White Participants Black Participants White Participants Black Participants White ParticipantsLS M e a n C h a n g e f ro m B a se lin e A. In�ammatory Lesion Reduction B. Nonin�ammatory Lesion Reduction -70% -50% -30% -10% LS M e a n C h a n g e f ro m B a se lin e Tazarotene 0.045% Lotion: • Black and White participants had a similar reduction in in�ammatory and nonin�ammatory lesions by week 12 • Lesion counts decreased over time in both Black and White participants (data not shown) • Greater percentage of Black and White participants achieved treatment success vs vehicle n=125 -60.4% n=137 -57.8% n=591 -57.6% n=600 -45.0% n=125 -52.6% n=137 -44.5% n=600 -40.7% n=591 -56.1% 0% 20% 40% 60% 80% 100% P e rc e n ta g e o f P a rt ic ip a n ts n=125 29.6% n=137 19.6% C. Treatment Successa n=591 31.2% n=600 16.7% Vehicle Lotion Tazarotene 0.045% Lotion Vehicle Lotion Tazarotene 0.045% Lotion Vehicle Lotion Tazarotene 0.045% Lotion *P<0.05; ***P<0.001 vs vehicle. aDefined as at least a 2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of ‘clear’ or ‘almost clear’. ITT, intent to treat; LS, least-squares. ■ Rates of TEAEs were similar for TAZ-treated Black and White participants; TEAEs were mostly mild or moderate and unrelated to treatment (Table 1) TABLE 1. Participants Reporting Any Treatment-Emergent Adverse Event (Safety Population, Pooled) Participants, n (%) Black Participants White Participants TAZ 0.045% Lotion (n=121) Vehicle Lotion (n=132) TAZ 0.045% Lotion (n=575) Vehicle Lotion (n=584) Reporting any TEAE 30 (24.8) 17 (12.9) 165 (28.7) 118 (20.2) Reporting any SAEa 1 (0.8) 1 (0.8) 3 (0.5) 3 (0.5) Discontinued due to a TEAEb 5 (4.1) 0 16 (2.8) 4 (0.7) Severity of TEAEs reported Mild 22 (18.2) 8 (6.1) 103 (17.9) 63 (10.8) Moderate 7 (5.8) 7 (5.3) 54 (9.4) 53 (9.1) Severe 1 (0.8) 2 (1.5) 8 (1.4) 2 (0.3) Relationship to study drug Related 15 (12.4) 1 (0.8) 68 (11.8) 8 (1.4) Unrelated 15 (12.4) 16 (12.1) 97 (16.9) 110 (18.8) Most common TEAEsc Application site pain 8 (6.6) 0 30 (5.2) 2 (0.3) Application site dryness 4 (3.3) 0 24 (4.2) 1 (0.2) Application site exfoliation 6 (5.0) 0 8 (1.4) 0 Viral URTIa 6 (5.0) 2 (1.5) 25 (4.3) 25 (4.3) aNo instances were considered by the investigator to be treatment related. bIncludes participants who discontinued study drug or prematurely discontinued from the study. cReported in ≥3% of participants in any treatment group. SAE, serious adverse event; TAZ, tazarotene; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection. FIGURE 4. Cutaneous Safety by Race (Safety Population, Pooled) 0% 20% 40% 60% 80% 100% P e rc e n ta g e o f P ar ti ci p an ts Scaling Erythema Hypopigmentation Hyperpigmentation TAZ Vehicle TAZ Vehicle TAZ Vehicle TAZ Vehicle P e rc e n ta g e o f P ar ti ci p an ts 0% 20% 40% 60% 80% 100% Scaling Erythema Hypopigmentation Hyperpigmentation TAZ Vehicle TAZ Vehicle TAZ Vehicle TAZ Vehicle Tazarotene-treated participants: • High baseline rates of hyperpigmentation (Black participants) and erythema (White participants) decreased by week 12 • Participant-reported tolerability assessments of itching, burning, and stinging were low in both groups (data not shown) B. White Participants A. Black Participants At Baseline: At Week 12: Mild Moderate Severe Mild Moderate Severe At Baseline: At Week 12: Mild Moderate Severe Mild Moderate Severe Data for “none” are not shown. N values were as follows: Black: TAZ baseline n=121, TAZ week 12 n=102, vehicle baseline n=132, vehicle week 12 n=121; White: TAZ baseline n=575, TAZ week 12 n=512, vehicle baseline n=584, vehicle week 12 n=532. TAZ, tazarotene 0.045% lotion. CONCLUSIONS ■ In two pooled phase 3 studies, tazarotene 0.045% lotion demonstrated efficacy in the treatment of moderate-to-severe acne in both White and Black participants • In White participants, tazarotene was significant versus vehicle for all 3 efficacy assessments • In Black participants, only reduction in noninflammatory lesions was significant for tazarotene versus vehicle; the lack of a statistical difference in the reduction of inflammatory lesions is likely due to the high response rate to vehicle in Black participants, whereas the statistical analysis of treatment success may have been limited in part by the small sample size ■ This new formulation of tazarotene was well tolerated compared with vehicle lotion, and treatment with tazarotene lotion led to improvements in inflammation-associated sequelae of acne, including hyperpigmentation ■ Tazarotene 0.045% lotion may be an effective and well tolerated treatment option for acne in patients with skin of color FIGURE 5. Postinflammatory Hyperpigmentation Improvement in Black Participants Baseline Baseline Week 12 Week 12 Two participants selected from a post hoc evaluation of study photographs to identify individuals who achieved improvement in postinflammatory hyperpigmentation. Individual results may vary. REFERENCES 1. Alexis AF. J Drugs Dermatol. 2014;13(6):s6-s10. 2. Leyden J, et al. Dermatol Ther (Heidelb). 2017;7(3):293-304. 3. Del Rosso JQ and Tanghetti E. J Drugs Dermatol. 2013;12(3)s53-58. 4. Tanghetti EA, et al. J Drugs Dermatol. 2019;18(6):542 5. Tanghetti EA, et al. J Drugs Dermatol. 2020;19(1)70-77. 6. Tanghetti EA, et al. J Drugs Dermatol. 2020;19(3)272-279. AUTHOR DISCLOSURES FCB has served as consultant, speaker, investigator for Galderma, LEO Pharma, Almirall, Cassiopea, Ortho Dermatologics, Investigators Encore, Foamix, Hovione, Aclaris, Cutanea. NB has received honoraria and investigator grants from Bausch Health. JW a consultant, speaker, advisor, and/or researcher for AbbVie, Ortho Dermatologics, Jansen Biotech, Dermira, Almirall, Brickell Biotech, DermTech, Scynexis. NS has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from Almirall, Actavis, Allergan, Anacor Pharmaceuticals, Auxilium Pharmaceuticals, Bausch Health, Bayer, Biorasi, BTG, Carma Laboratories, Cassiopea, Celgene Corporation, Cutera, Cynosure, DUSA Pharmaceuticals, Eclipse Medical, Eli Lilly and Company, Endo International, EndyMed Medical, Ferndale Laboratories, Galderma, Gerson Lehrman Group, Hydropeptide, Merz Aesthetics, Neostrata, Novartis, Nutraceutical Wellness, Palomar Medical Technologies, Prescriber’s Choice, Regeneron, Roche Laboratories, Samumed, Solta Medical, Storz Medical AG, Suneva Medical, Vanda Pharmaceuticals, and Venus Concept. ST has acted as an investigator for Ortho Dermatologics. EG is an employee of Ortho Dermatologics and may hold stock or stock options in its parent company. AL and SH are employees of Bausch Health US, LLC and may hold stock and/or stock options in its parent company.