Introduction • Acne vulgaris is a prevalent chronic, inflammatory skin disorder that affects most of the population at some point in their life1 • Oral minocycline and doxycycline are considered first-line therapy for the treatment of moderate-to-severe acne but are associated with potentially serious systemic side effects2 • FMX101 4% is the first stable topical foam formulation of minocycline that has been shown to be an effective and well-tolerated treatment for acne – Phase 2 clinical trial – 2 double-blind Phase 3 pivotal studies, Study FX2014-04 and Study FX2014-053,4 • A third Phase 3 study (FX2017-22) was conducted to further evaluate the efficacy and safety of daily topical administration of FMX101 4% vs vehicle foam for a period of 12 weeks in the treatment of moderate-to-severe acne vulgaris – Multicenter, randomized, double-blind, vehicle-controlled, 2-arm study Methods • FX2017-22, a Phase 3 multicenter (89 sites), randomized, double-blind, vehicle-controlled, 2-arm study, further evaluated the efficacy and safety of topical FMX101 4% in the treatment of moderate-to-severe acne vulgaris (Figure 1) – Subjects were randomized 1:1 to receive either FMX101 4% or vehicle foam – Foam was self-applied once-daily for 12 weeks Figure 1. Study design Methods 3 ➢ FX2017-22, a Phase 3 multicenter (89 sites), randomized, double-blind, vehicle-controlled, 2-arm study, further evaluated the efficacy and safety of topical FMX101 4% in the treatment of moderate-to-severe acne vulgaris (Figure 1) o Subjects were randomized 1:1 to receive either FMX101 4% or vehicle foam o Foam was self-applied daily for 12 weeks • • AE=adverse event; IGA=Investigator’s Global Assessment. *Due to quality issues identified at one center, 19 subjects were prospectively removed from the intent-to-treat (ITT) population. Figure 1. Study design. • • ‒ ‒ • • • • AE=adverse event; IGA=Investigator’s Global Assessment. aDue to quality issues identified at one center, 19 subjects were prospectively removed from the intent-to-treat (ITT) population. Results • 1507 subjects were enrolled in the study • Baseline demographics and disease characteristics are shown in Table 1 Table 1. Baseline demographics and disease characteristics FMX101 4% (n=738) Vehicle Foam (n=750) Mean age, years 20.2 20.6 Age distribution, n (%) 9-12 yr 13-17 yr >18 yr 42 (5.7) 321 (43.5) 375 (50.8) 41 (5.5) 309 (41.2) 400 (53.3) Male, n (%) Female, n (%) 278 (37.7) 460 (62.3) 281 (37.5) 469 (62.5) Ethnicity, n (%) White Black Other 571 (77.4) 125 (16.9) 42 (5.7) 560 (74.7) 144 (19.2) 46 (6.1) Inflammatory lesion count, mean (SD) 30.7 (8.89) 30.8 (8.27) Noninflammatory lesion count, mean (SD) 49.7 (19.70) 49.6 (19.47) Total lesion count, mean (SD) 80.4 (22.7) 80.3 (22.4) IGA score, n (%) 3 – Moderate 4 – Severe 620 (84.0) 118 (16.0) 626 (83.5) 124 (16.5) Figure 2. Absolute change in inflammatory lesion count from baseline at week 12 • At week 12, subjects treated with FMX101 4% had a statistically significantly greater reduction in the number of inflammatory lesions from baseline as compared with the vehicle treatment group, P<0.0001 (Figure 2) ANCOVA, ITT population, MI. ANCOVA=analysis of covariance. Figure 3. IGA treatment success at week 12 • At week 12, the proportion of subjects achieving IGA treatment success in the FMX101 4% treatment group was statistically significantly higher than in the vehicle treatment group, P<0.0001 (Figure 3) Cochrane Mantel-Haenszel test, stratified by analysis center, ITT population, MI. Figure 4: Absolute change of noninflammatory lesion count at week 12 • At week 12, the absolute change in noninflammatory lesion count in the FMX101 4% treatment group was statistically significantly greater than in the vehicle treatment group, P<0.01 (Figure 4) ANCOVA, ITT population, MI. Figure 5. Percentage change from baseline to week 12 in inflammatory lesions by visit • The percentage reduction in inflammatory lesions was statistically significantly greater for FMX101 4% vs vehicle at all visits – week 3, 6, 9, and 12 (Figure 5) ANCOVA, ITT population, observed cases. *P≤.0001. Table 2. Summary of treatment-emergent adverse events (TEAEs) in safety populationa FMX101 4% (n=737) Vehicle (n=747) Subjects with any TEAE, n (%) 193 (26.2) 183 (24.5) Number of TEAEs 255 235 Subjects with any serious TEAE, n (%) 1 (0.1) 4 (0.5) Number of serious TEAEs 1b 5c aSafety population includes all randomized subjects who used at least 1 dose of study drug. bSpontaneous abortion. cGastrointestinal disorders, spontaneous abortion, cholecystitis. Table 3. Summary of subject discontinuation FMX101 4% Vehicle Subjects discontinued, n (%) 89 (12.1) 106 (14.1) Reason for discontinuation Adverse event Abnormal laboratory result Lost to follow-up Subject request Protocol deviation Other 3 (0.4) 1 (0.1) 34 (4.6) 36 (4.9) 6 (0.8) 9 (1.2) 2 (0.3) 0 (0.0) 39 (5.2) 53 (7.1) 4 (0.5) 8 (1.1) Table 4. Nondermal and dermal AEs FMX 101 4% Vehicle One or more, n (%) 193 (26.2) 183 (24.5) Nondermal AEs in ≥1% of subjects, n (%) URTI Viral URTI Headache CK increased Influenza 31 (4.2) 16 (2.2) 14 (1.9) 14 (1.9) 11 (1.5) 26 (3.5) 22 (2.9) 11 (1.5) 6 (0.8) 4 (0.5) Dermal AEs in ≥1% of subjects, n (%) Acne 22 (3.0) 26 (3.5) CK=creatine phosphokinase; URTI=upper respiratory tract infection; UTI=urinary tract infection. Table 5. Facial local tolerability assessments at week 12, scale 0 (none) to 3 (severe) Facial Local Tolerability Assessment,a n (%) FMX101 (n=737) Vehicle Foam (n=747) 0=None 1=Mild 2= Moderate 3= Severe 0=None 1=Mild 2= Moderate 3= Severe Erythema 515 (82.7) 100 (16.0) 11 (1.8) 0 (0.0) 514 (82.5) 98 (15.7) 11 (1.8) 0 (0.0) Dryness 568 (90.7) 53 (8.5) 5 (0.8) 0 (0.0) 550 (88.3) 68 (10.9) 4 (0.6) 1 (0.2) Hyperpigmentationb 536 (85.6) 75 (12.0) 14 (2.2) 1 (0.2) 515 (82.7) 90 (14.4) 17 (2.7) 1 (0.2) Skin Peeling 607 (97.0) 18 (2.9) 1 (0.2) 0 (0.0) 587 (94.2) 33 (5.3) 2 (0.3) 1 (0.2) Itching 588 (93.9) 30 (4.8) 7 (1.1) 1 (0.2) 577 (92.6) 40 (6.4) 6 (1.0) 0 (0.0) aBased on safety population. bThe term hyperpigmentation was most commonly used to describe localized post-inflammatory darkening of the affected skin. Safety Summary • FMX101 4% was generally safe and well tolerated • Treatment-emergent adverse events (TEAEs) were few in type and frequency; most were mild in severity • The most common adverse event in the study was upper respiratory tract infection, with similar frequency in the treatment arm (4.2%) and vehicle arm (3.5%) • There were no treatment-related serious adverse events, and there was low subject discontinuation due to a TEAE (Tables 2 and 3) • Cutaneous TEAEs were comparable in frequency in the FMX101 4% treatment group and vehicle group; the most common cutaneous AE (≥1% of subjects) was acne (Table 4) – >95% of subjects had none or mild signs and symptoms at week 12 assessment of dermal tolerability (Table 5) • In total, 5 subjects discontinued from Study 22 due to a TEAE – 3 subjects for FMX101 4% 2 subjects for vehicle group Conclusions • The results of the Phase 3 study showed that FMX101 4% was safe and effective for the treatment of moderate-to-severe acne • The study met both co-primary end points of absolute change from baseline in inflammatory lesion count and proportion with IGA treatment success at week 12 – Significant reduction in number of both inflammatory and noninflammatory lesions at week 12 from baseline in FMX101 4% treatment group vs vehicle treatment group – Significant improvement in IGA treatment success at week 12 in FMX101 4% treatment group vs vehicle treatment group • The safety profile of FMX101 was found to be consistent with that determined from the 2 prior Phase 3 studies (FX2014-04 and FX2014-05) FMX101 4% Topical Minocycline Foam for the Treatment of Moderate-to-Severe Acne Vulgaris: Efficacy and Safety From a Phase 3 Randomized, Double-Blind, Vehicle-Controlled Study Joseph Raoof, MD1, Deirdre Hooper, MD2, Angela Moore, MD3, Martin Zaiac, MD4, Tory Sullivan, MD5, Leon Kircik, MD6, Edward Lain, MD7, Jasmina Jankicevic, MD8, Iain Stuart, PhD8 1Encino Research Center, Encino, CA; 2Delricht Research, New Orleans, LA; 3Arlington Research Center, Arlington, TX; 4Sweet Hope Research Specialty, Inc., Miami Lakes, FL; 5Sullivan Dermatology, North Miami Beach, FL; 6Mount Sinai Hospital, New York, NY; 7Austin Institute for Dermatology, Austin, TX; 8Foamix Pharmaceuticals, Inc, Bridgewater, NJ. Disclosures This study was funded by Foamix Pharmaceuticals. Dr. Joseph Raoof, Dr. Deirdre Hooper, Dr. Martin Zaiac, Dr. Tory Sullivan, and Dr. Edward Lain served as investigators for Foamix. Dr. Angela Moore is an investigator, consultant, and/or speaker for Abbvie, Aclaris, Actavis, Astellas, Asubio, Biofrontera, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, Coherus, Dermavant, Dermira, Eli Lilly, Foamix, Galderma, Incyte, Janssen, Leo, Mayne, Novartis, Parexel, Pfizer, Therapeutics, Verrica. Dr. Leon Kircik is an investigator and consultant for Foamix. Dr. Jasmina Jankicevic is a consultant for Foamix Pharmaceuticals. Dr. Iain Stuart is an employee of Foamix Pharmaceuticals. Acknowledgment Editorial support was provided by p-value communications. Presented at the Fall Clinical Dermatology Conference; October 18-21, 2018; Las Vegas, Nevada. Results (cont.) ➢ At Week 12, subjects treated with FMX101 4% had a statistically significantly greater reduction in the number of inflammatory lesions from baseline as compared with the vehicle treatment group, p<0.0001 (Figure 2) Figure 2. Absolute change in inflammatory lesion count from baseline at week 12. 5 ‒ ‒ ANCOVA, ITT population, MI. ANCOVA=analysis of covariance; CI=confidence interval; LSM=least squares mean; MI=multiple imputation. References 1. Thiboutot DM, Dreno B, Abanmi, et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018; 78(2S1):S1-S23.e1. 2. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016. http://dx.doi.org/10.1016/j.jaad.2015.12.037. 3. Schemer A, Shiri J, Mashiah J, et al. Topical minocycline foam for moderate to severe acne vulgaris: Phase 2 randomized double-blind, vehicle-controlled study results. J Am Acad Dermatol. 2016;74(6):1251-1252. 4. Gold LS, Dhawan S, Weiss J, et al. A novel minocycline foam for the treatment of moderate-to-severe acne vulgaris: results of two randomized, double-blind, Phase 3 studies. J Am Acad Dermatol. 2018 Aug 27. Epub ahead of print. ➢ At Week 12, the proportion of subjects achieving IGA treatment success in the FMX101 4% treatment group was statistically significantly higher than in the vehicle treatment group, p<0.0001 (Figure 3) Figure 3. IGA treatment success at week 12. Results (cont.) 6Cochrane Mantel-Haenszel test, stratified by analysis center, ITT population, MI 7 Results (cont.) * ANCOVA, ITT population, observed cases ** ANCOVA, ITT population, MI P<0.05 Figure 4: Absolute Change of Non-Inflammatory Lesion Count at Week 12. ➢ At Week 12, the absolute change in non-inflammatory lesion count in the FMX101 4% treatment group was statistically significantly greater than in the vehicle treatment group, p<0.05 (Figure 4) ‒ ‒ Results (cont.) 8 ANCOVA, ITT population, observed cases. *P≤.0001. Figure 5. Percentage change from baseline to week 12 in inflammatory lesions by visit ➢ The percentage reduction in inflammatory lesions was statistically significantly greater for FMX101 4% vs vehicle at all visits – week 3, 6, 9, and 12 (Figure 5)