Presented at the 2020 Fall Clinical Dermatology Conference, October 29 - November 1, 2020. Treatment Success in Mild Psoriasis Patients With Fixed-Combination Calcipotriene and Betamethasone Dipropionate (Cal/BD) Foam: Results From the PSO-FAST Trial Karen A. Veverka, PhD,1 Jes B. Hansen, PhD,1 Maria Yaloumis, PharmD,1 Leon Kircik, MD,2 and Linda Stein Gold, MD3 1LEO Pharma, Madison, NJ; 2Icahn School of Medicine at Mount Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; 3Henry Ford Hospital, Detroit, MI Introduction • Psoriasis is a chronic skin disease affecting approximately 2% of the worldwide population characterized by sharply demarcated, scaling, and erythematous plaques that may be painful and often severely pruritic1 • While topical therapy is the regimen of choice for patients with less extensive disease,2 very few of these therapies have been demonstrated effective for mild psoriasis – Treatment success in this population requires that visible disease be completely cleared (i.e., improvement of Investigator’s Global Assessment (IGA) score from 2 to 0) • Corticosteroids and vitamin D analogues are among the most common treatments that are either used alone or in combination2,3 • Topical, fixed-combination calcipotriene (50 µg/g) plus betamethasone dipropionate (0.5 mg/g; Cal/BD) cutaneous foam is indicated for the treatment of plaque psoriasis in patients 12 years and older4 – In a Phase III, double-blind, randomized study that included patients with all severities of psoriasis (PSO-FAST), Cal/BD foam was efficacious and well tolerated, and also provided rapid treatment responses with significant itch relief3 Objective • To compare the efficacy of treatment with Cal/BD foam to that of treatment with vehicle for up to 4 weeks in patients with mild psoriasis vulgaris by performing a post hoc analysis of the PSO-FAST trial Materials and Methods Study Design • PSO-FAST was a Phase III, randomized, multicenter (US), double-blind, vehicle-controlled, 4-week study (NCT01866163) • 426 patients were randomized (3:1) to Cal/BD foam or foam vehicle once daily for up to 4 weeks Figure 1. Study Design KEY INCLUSION CRITERIA KEY EXCLUSION CRITERIA Treatments within specified time periods prior to randomization: • Systemic biological therapies (4-16 weeks/5 half-lives) • All other systemic treatments (4 weeks) • Non-marketed drugs (4 weeks/5 half-lives) • PUVA therapy (4 weeks) • UVB therapy (2 weeks) • Topical anti-psoriatic treatment (2 weeks) • ≥18 years of age • Males and non-pregnant females • Psoriasis diagnosis ≥6 months • IGAa of at least mild on trunk and/or limbs • 2-30% BSA on trunk and/or limbs • mPASI score ≥2 RANDOMIZED 3:1 Cal/BD Foam self-applied 1/day (n=323) Vehicle Foam self-applied 1/day (n=103) Day 0 Week 1 Week 2 Week 4 ENDPOINT ASSESSMENTS • Percent of patients achieving treatment success at Week 4b • mPASI-75 at Week 4 • Percent reduction in mPASI from baseline to Weeks 1, 2, and 4 aInvestigator’s Global Assessment (IGA) of disease severity was scored on a 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe. bTreatment success for patients with mild disease severity at baseline was defined as clear (IGA=0). Results Patient Population • At baseline, 65/426 patients had mild plaque psoriasis • Baseline demographics and disease characteristics are shown in Table 1 • Overall, treatment groups were well balanced for patient characteristics and baseline demographics within this subpopulation • Both mean BSA and mean mPASI at baseline were comparable between groups Table 1. Baseline Demographics and Disease Characteristics for Randomized Patients With Mild Psoriasis (IGA=2) Baseline Characteristic Cal/BD Foam (n=50) Vehicle Foam (n=15) Overall (N=65) Mean Age, years 48.6 42.2 47.2 Median Age, years (range) 52.5 (19-79) 38.0 (20-74) 50.0 (19-79) Male, % 56.0 46.7 53.8 Fitzpatrick Skin Type, % Type I 2.0 0.0 1.5 Type II 42.0 20.0 36.9 Type III 26.0 40.0 29.2 Type IV 18.0 20.0 18.5 Type V 6.0 20.0 9.2 Type VI 6.0 0.0 4.6 Mean BMI, kg/m2 31.5 31.5 31.5 Mean PSO Duration, years 16.0 9.1 14.4 Mean BSA, % (SD) 4.5 (2.6) 5.7 (4.2) 4.8 (3.1) Mean mPASI (range) 4.7 (2-16) 5.0 (2-8) 4.7 (2-16) Efficacy: IGA Treatment Success • At Week 4, significantly more patients with mild psoriasis achieved treatment success with Cal/BD foam than foam vehicle (30.6% vs 0.0%, P<.001) (Figure 2) – Treatment success was observed as early as Week 2 with Cal/BD foam vs vehicle (8.2% vs 0%) (data not shown) Figure 2. IGA Treatment Success at Week 4 for Patients With Mild, Moderate, or Severe Psoriasis at Baseline 30.6% 60.0% 37.9% 0.0% 4.2% 7.7% 0 25 50 75 100 Mild Moderate Severe Tr ea tm en t su cc es s (% o f p ati en ts ) Cal/BD Foam Vehicle Foam P<.001 P=.019 P=.048 Mantel-Haenszel odds of treatment success in Cal/BD group relative to vehicle group. Efficacy: Severity Outcomes • Mild patients achieved significantly greater reductions in BSA (Figure 3A) and mPASI scores (Figure 3B) relative to baseline with Cal/BD foam vs vehicle foam – The significant improvements were seen as early as Week 1 and persisted to Week 4 • mPASI-75 was significantly greater with Cal/BD foam vs vehicle foam (49% vs 7.1%, P=.023) at Week 4 (Figure 4). Figure 3. Psoriasis Severity Outcomes for Patients With Mild PSO at Baseline -35.5% -55.3% -71.9% -15.2% -25.0% -27.7% -100 -75 -50 -25 0 Week 1 Week 2 Week 4 Re du cti on in m PA SI fr om b as el in e (% ) -1.2 -1.8 -2.7 0.1 -0.5 -0.6 -5 -4 -3 -2 -1 0 1 Week 1 Week 2 Week 4 A bs ol ut e BS A r ed uc ti on fr om b as el in e A B Cal/BD Foam Vehicle Foam P=.007 P=.057 P<.001 P=.053 P=.003 P<.001 A, Absolute Reduction in BSA From Baseline to Weeks 1, 2, and 4. B, Percent Reduction in mPASI From Baseline to Weeks 1, 2, and 4. Figure 4. mPASI-75 for Patients With Mild Disease Severity at Baseline P=.24 P=.083 P=.023 12.2% 30.6% 49.0% 0.0% 7.7% 7.1% 0 25 50 75 100 Week 1 Week 2 Week 3 Cal/BD Foam Vehicle Foam m PA SI -7 5 (% ) Mantel-Haenszel odds of treatment success in Cal/BD group relative to vehicle group, adjusted for pooled center. Conclusions • In this post hoc analysis, once-daily fixed-dose combination Cal/BD foam was efficacious in treating mild plaque psoriasis – Importantly, while numerous other topical and systemic therapies are available for psoriasis, very few have demonstrated efficacy in this subpopulation • These important results establish treatment success for Cal/BD foam in mild psoriasis, a population in which efficacy is difficult to demonstrate since the treatment must completely clear visible disease to be considered effective • The once-daily, Cal/BD foam may provide a valuable treatment option for patients with mild plaque psoriasis References 1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2009;58(5):826-850. 2. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management and treatment of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2009;60:643-659. 3. Leonardi C, Bagel J, Yamauchi P, et al. Efficacy and safety of calcipotriene plus betamethasone dipropionate aerosol foam in patients with psoriasis vulgaris – a randomized phase III study (PSO-FAST). J Drugs Dermatol. 2015;14(2):1468-1477. 4. Enstilar (calcipotriene and betamethasone dipropionate) foam Prescribing Information, Madison, NJ: LEO Pharma, Inc. Disclosures Drs. KA Veverka, JB Hansen and M Yaloumis are employees of LEO Pharma Inc. Dr. Kircik has served as a research investigator, speaker, and consultant for LEO Pharma, Inc. Dr. L Stein Gold serves as a consultant, speaker, advisory board participant, or investigator for LEO Pharma inc., Taro Pharmaceutical Industries Ltd., and Mayne Pharma. Funding This study was funded by LEO Pharma Inc. Abbreviations BMI, body mass index; BSA, body surface area; Cal/BD, calcipotriene/betamethasone dipropionate; IGA, Investigator’s Global Assessment; mPASI, modified (excluding head) psoriasis area and severity index; mPASI-75, 75% reduction in the mPASI; PSO, psoriasis; PUVA, psoralen combined with Ultraviolet A; SD, standard deviation; UVB, Ultraviolet B. Acknowledgments Editorial support was provided by p-value communications.