ACKNOWLEDGEMENTS Study funded by Galderma Research & Development, SNC, and editorial/poster support provided by Galderma Laboratories, L.P. METHODS Study 1 • A 12 O tetradecanoylphorbol-13-acetate (TPA)-induced inflammation model was designed to investigate the anti-inflammatory effect of IVM in BALB/c ByJ Rj mice. • Ear edema was induced in the right ear of female mice by topical application of TPA 0.01%, followed by treatment with: - Topical vehicle - IVM (0.1% to 1%) - BR (0.2%) - IVM+BR - An anti-inflammatory control (betamethasone valerate 0.01% or indomethacin 5%) • Right ear thickness (μm) was measured using a micrometer pre- and 6 hours after TPA application Study 2 • This was a multicenter, randomized, double-blind, vehicle-controlled, and parallel group comparison study that included subjects with moderate to severe rosacea (Investigator Global Assessment [IGA] ≥3, scale 0-4), characterized by persistent diffuse moderate to severe erythema (Clinician Erythema Assessment [CEA] ≥3, scale 0-4) and inflammatory lesions ([IL] 15-70 papules/pustules). • Treatments - Randomized 1:1:2, 2 active and 1 vehicle group, respectively - IVM (1%) + BR (0.33%) active treatment groups: · IVM+BR/12W subgroup (n = 49): Once daily IVM + BR for 12 weeks · IVM+BR/8W subgroup: (n = 46): Once daily IVM + BR vehicle for 4 weeks; followed by IVM + BR for the remaining 8 weeks - Vehicle group: · Once daily IVM vehicle and BR vehicle for 12 weeks (vehicle group, n = 95) - A daily skin care regimen of gentle cleanser, moisturizing lotion and facial moisturizer SPF 15 sunscreen • Efficacy and safety endpoints - IGA success (0/1 [clear/almost clear], 5-point scale, week 12, 3 hours after BR application), IGA at each visit, CEA, 100% reduction in IL count, and subject global improvement of rosacea - AEs were monitored throughout the study RESULTS Study 1 • Anti-inflammatory synergy was observed between IVM and BR in the mouse model • IVM+BR had a similar effect on ear edema at 6 hours when compared with a potent corticosteroid or NSAID (Figure 1 and 2) Study 2 • Subjects who began IVM+BR treatment at baseline had an improved rate of IGA success when compared with both vehicle and subjects who began BR treatment at week 8 (Figure 3) • Subjects who began IVM+BR treatment at baseline had improved CEA assessments at week 12 when compared with both vehicle and subjects who began BR treatment at week 8 (Figure 4) • Subjects who began IVM+BR treatment at baseline were more likely to achieve a 100% reduction in lesions at week 12 when compared with both vehicle and subjects who began BR treatment at week 8 (Figure 5) Safety • Only 8 treatment-related AEs in 6 subjects (3.2%) were reported; none were serious or severe. • One related AE leading to discontinuation (allergic dermatitis on the chest) was reported in the IVM+BR/8W group. • Related worsening of rosacea was observed in similar frequency with 1 (2.2%) AE in the active IVM+BR groups vs. 3 (2.1%) AEs in the vehicle group. INTRODUCTION • Rosacea is often characterized by persistent centrofacial erythema and recurrent inflammatory papules/pustules - The pathophysiology of papulopustular rosacea (PPR) is not fully understood - Multiple immune, inflammatory, and vascular processes are likely involved • Ivermectin 1% (IVM) cream has anti-inflammatory properties and has been shown to be effective against papules/pustules of erythema1,2,3 - Ivermectin treatment reduces pro-inflammatory cytokines and chemokines, inhibits leukocytes, and modulates the cathelicidin pathway • Brimonidine 0.33% (BR) gel has been shown to be effective against persistent facial erythema2 - Brimonidine is an alpha 2 adrenergic agonist responsible for vasoconstriction of superficial blood vessels • Two recent studies investigate IVM and BR when used in combination for the treatment of PPR THE ANTI-INFLAMMATORY PROPERTIES OF IVERMECTIN AND BRIMONIDINE IN THE TREATMENT OF PAPULOPUSTULAR ROSACEA Linda Stein Gold, MD1; Edward Lain, MD2; Alison Harvey, PhD, MS3 1Department of Dermatology, Henry Ford Medical Center, Detroit, MI, USA; 2Austin Institute for Clinical Research, Pflugerville, TX; 3Galderma Laboratories, L.P., Fort Worth, TX SOO.P-RD105069-03 SUMMARY • Rosacea therapy requires a global and patient specific approach that targets its varied symptoms and mechanisms, including both the inflammatory pathways and vascular components of the disease. • In the mouse model: – IVM significantly reduced ear skin swelling – BR acted synergistically with IVM to enhance anti-inflammatory activity • In the clinical study: – Simultaneous administration of IVM 1% cream with BR 0.33% gel demonstrated superior efficacy compared to their respective vehicles for the treatment of moderate to severe rosacea – The IVM + BR association was well tolerated, with less than 5% related AEs • The regimen of IVM+BR is a safe and effective option for the comprehensive management of this complex disease • These studies suggest that initiating rosacea therapy with IVM+BR, along with a complete daily skin care regimen, may improve and accelerate the efficacy of IVM treatment, without impairing tolerability • Treating with IVM+BR from the start was more effective than an initial period of IVM treatment alone followed by IVM+BR REFERENCES 1. Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13:316-323. 2. Abokwidir M, et al. J Dermatol Treat. 2015;26(4):379-80. 3. Thibaut de Menonville S, et al. Dermatol Ther (Heidelb). 2017 epub 4. Fowler J Jr, Jackson M, Moore A, et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle- controlled pivotal studies. J Drugs Dermatol. 2013;12:650-656. 5. Di Nardo A, et al. J Am Acad Dermatol. 2016 Jun;74(6):1086-92. 200 300 400 500 600 Vehicle Betamethasone valerate Ivermectin 0.3%+Brimonidine 0.2% Ivermectin 0.3% Brimonidine 0.2% * * * * * Ea r T hi ck ne ss (µ m ): M ea n + /- SD * P . 0 1 * * P < . 0 0 1 200 250 300 350 400 450 500 Vehicle Indomethacin Ivermectin 1% * * * * * * * * P . 0 1 * * P < . 0 0 1 Ea r T hi ck ne ss (μ m ): M ea n + /- SD Ivermectin 1%+Brimonidine 0.2% Brimonidine 0.2% 4.1 22.4 42.9 61.2 4.3 13.0 30.4 50.0 5.3 9.5 24.2 36.8 0 10 20 30 40 50 60 70 Baseline Week 4 Week 8 Week 12 Pe rce nt o f S ub je cts A ch ie vin g IG A Su cce ss (I GA 0 o r 1 ) IVM+BR/12W (N = 46) IVM+BR/8W (BR Vehicle) Vehicle (n = 95) IVM+BR/8W (BR Active) P = .003 P = .02 P = .04 (n = 49) 15.1 29.3 29.5 25.6 39.0 45.5 0 10 20 30 40 50 60 70 80 Clear Skin Almost Clear 40.7 Success 68.3* Success 75.0* Success Pe rce nt o f S ub je cts IVM+BR 12WVehicle IVM+BR 8W * P = .001 4.2 6.5 16.3 0 2 4 6 8 10 12 14 16 18 Vehicles IVM + BR / 8 Weeks IVM + BR / 12 Weeks Pe rc en t o f S ub je cts w ith 1 00 % R ed uc tio n in In fla m m at or y L es io n Co un t P = .015 Figure 1. Ear Edema Measured 6 Hours Post-treatment Figure 2. Ear Edema Measured 1 Hour Post-treatment Figure 3. IGA Success Figure 4. CEA at Week 12, Hour 3 Figure 5. Percent of Subjects Achieving 100% IL Reduction Betamethasone valerate is a potent corticosteroid. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID). Betamethasone valerate is a potent corticosteroid. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID). FC17PosterGaldermaSteinGoldAntiInflammatoryProperties.pdf