LEO Pharma presents results from study of twice-weekly Enstilar® (calcipotriene and betamethasone dipropionate) Foam for topical use in long-term maintenance treatment of plaque psoriasis

• New results from the PSO-LONG clinical trial are the first to provide long-term maintenance data for plaque psoriasis with a twice-weekly topical treatment with Enstilar^®(calcipotriene and betamethasone dipropionate) Foam
• Plaque psoriasis is a chronic, multifactorial disease affecting nearly 80% of the 125 million people living with psoriasis worldwide(1,2)
• LEO Pharma is committed to building on its more than 30-year heritage of pursuing innovative products for patients affected by psoriasis and other chronic skin conditions

BALLERUP, Denmark, JUNE 12, 2020 – LEO Pharma A/S, a global leader in medical dermatology, today presented results from the Phase 3 PSO-LONG clinical trial. PSO-LONG compared the efficacy and safety of twice-weekly Enstilar^® (calcipotriene and betamethasone dipropionate)Foam, versus foam vehicle for long-term (52-week) maintenance treatment for adult patients with plaque psoriasis.(3,4) Results were presented as ePosters online at the American Academy of Dermatology (AAD) Virtual Meeting Experience (VMX) 2020.

Use of twice-weekly Enstilar (calcipotrieneand betamethasonedipropionate) Foam as a long-term maintenance treatment is investigational and is not approved in any country, and safety and efficacy are currently being evaluated by regulatory authorities.

Psoriasis is a chronic, multifactorial disease that primarily affects the skin and often requires long-term treatment.(5) Plaque psoriasis is the most common type of psoriasis characterized by an overactive immune system that causes inflammation of the skin and speeds up skin cell growth, which leads to plaque development.(1,5) Topical treatments are often prescribed in mild-to-moderate cases of plaque psoriasis.(1)

Enstilar (calcipotrieneand betamethasonedipropionate) Foam met the primary endpoint in the PSO-LONG trial by prolonging time to first relapse versus foam vehicle (56 days vs. 30 days).(3,4)

“These results, as demonstrated by the primary endpoint, introduce new clinical data for the treatment of adult patients with plaque psoriasis,” said Mark Lebwohl*, M.D., Waldman Chair of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City and Principal Investigator for the PSO-LONG trial. “This first-of-its kind year-long study and resulting data demonstrate that the fixed-dose combination of calcipotriene and betamethasone dipropionatefoam both reduced relapses and increased the number of relapse-free days versus foam vehicle.”

Safety was evaluated as effects on calcium homeostasis and on hypothalamic-pituitary-adrenal (HPA) axis with long-term use of twice-weekly calcipotriene and betamethasone dipropionatefoam, among other safety assessments. No clinically relevant effects on calcium metabolism or the HPA axis were observed. The rate of adverse events (AEs) was comparable across treatment groups.(4)

The AAD VMX 2020featured three ePosters highlighting efficacy, safety and open label data from the Phase 3 PSO-LONG trial:

• Long-term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam: results of a Phase III randomized controlled trial.
• Safety of long-term proactive management with fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam in patients with psoriasis vulgaris: results of a Phase III, multicentre, randomized, 52-week, vehicle-controlled trial.
• Results from the open-label treatment period of a long-term proactive management phase III trial using fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam.

In the trial:

• 650 patients aged 18 or older were included in a four-week open label phase where each received once-daily calcipotriene and betamethasone dipropionatefoam.
• 521 patients (80%) achieved treatment success (Physician Global Assessment [PGA] “clear”/”almost clear” with a minimum two-grade improvement from baseline) and were then randomized 1:1 to twice-weekly administration of either calcipotriene and betamethasone dipropionatefoam or vehicle foam for 52 weeks.
• In both arms, patients with relapse received once-daily calcipotriene and betamethasone dipropionatefoam for four weeks.
• 82% of patients had a PGA score of ‘moderate’ at baseline.
• 251 randomized patients (46%) completed the long-term study.

Eligibility requirements:

To have participated in the trial, patients must have:

• Been 18 years of age or older,
• Truncal and/or limb psoriasis involving 2-30% of body surface area, and
• PGA greater than or equal to mild and modified psoriasis area, and a severity index score (mPASI) of greater than or equal to two at first visit.

Results:

• The median time to first relapse was 56 days for calcipotriene and betamethasone dipropionatefoam vs. 30 days for foam vehicle.
• Risk of first relapse was 43% lower with calcipotriene and betamethasone dipropionatefoam vs. foam vehicle (HR, 0.57; 95% CI, 0.47-0.69; p<0.001).
• Rate of relapse over one year was 46% lower for the calcipotriene and betamethasone dipropionatefoam group vs. the foam vehicle group (95% CI, 37-54%; p<0.001).
• Rate of serious AEs per 100 patient-years was comparable (8.3, calcipotriene and betamethasone dipropionatefoam [n=272]; 7.9 foam vehicle [n=273]), as was rate of treatment-related AEs (2.8, calcipotrieneand betamethasonedipropionate foam [n=272]; 4.5 foam vehicle [n=273]).

Find additional information about the PSO-LONG trial at www.clinicaltrials.gov.

*Dr. Lebwohl is a paid consultant to LEO Pharma.

About Psoriasis
Psoriasis is a chronic, systemic inflammatory disease that primarily affects the skin in 125 million people worldwide.(1,2) About 80% of patients are affected by plaque psoriasis, the most common clinical form of psoriasis.(1) The symptoms of plaque psoriasis are itchy or painful, scaly, inflamed plaques. Plaques may appear anywhere on the body, but often appear on the scalp, knees, elbows and torso.Psoriasis is characterized as mild when less than 3% of the body is affected and moderate to severe when more than 3% of the body is affected.(6) Topical treatments are often prescribed in mild-to-moderate cases of plaque psoriasis.(1)

About Enstilar (calcipotriene and betamethasone dipropionate) Foam
Enstilar Foam is a combination of calcipotriene, a vitamin D analog, and betamethasone dipropionate, a corticosteroid.

U.S. FDA APPROVED INDICATION FOR ENSTILAR (calcipotriene and betamethasone dipropionate) Foam
Enstilar (calcipotriene and betamethasone dipropionate) Foam is indicated for the topical treatment of plaque psoriasis in patients 12 years and older. Apply Enstilar Foam to affected areas once daily for up to 4 weeks. Discontinue use when control is achieved. Instruct patients not to use more than 60 grams every 4 days.

IMPORTANT SAFETY INFORMATION

For topical use only. Enstilar Foam is not for oral, ophthalmic or intravaginal use and should not be applied on the face, groin or axillae or if skin atrophy is present at the treatment site. Do not use with occlusive dressings. Patients should wash hands after application.

WARNINGS AND PRECAUTIONS

• Flammability: The propellants in Enstilar Foam are flammable. Instruct patients to avoid fire, flame, and smoking during and immediately followingapplication.
• Hypercalcemia and Hypercalciuria: Hypercalcemia and hypercalciuria have been reported. If either occurs, discontinue until parameters of calcium metabolismnormalize.
• Effects on Endocrine System: Can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency duringand after withdrawal of treatment. Risk factors include the use of high-potency topical corticosteroid, use over a large surface area or to areas under occlusion, prolonged use, altered skin barrier, liver failure, and young age. Modify use should HPA axis suppression develop.
  Cushing’s syndrome, hyperglycemia and glucosuria may occur due to the systemic effects of the topical corticosteroid.

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios.

• Allergic Contact Dermatitis:Allergic contact dermatitis has been observed withtopical calcipotriene and topicalcorticosteroids.
• Ophthalmic Adverse Reactions: May increase the risk of posterior subcapsularcataracts and glaucoma. Avoid contact of Enstilar Foam with eyes. Enstilar Foam may cause eye irritation. Advise patients to report any visual symptoms and consider referral to an ophthalmologist forevaluation.

ADVERSE REACTIONS

• Adverse reactions reported in <1% of adult subjects included: application site irritation, application site pruritus, folliculitis, skin hypopigmentation, hypercalcemia, urticaria, and exacerbation of psoriasis.
• Adverse reactions reported in <1% of pediatric subjects (12-17 years of age) were acne, erythema, application site pain, and skin reactions.

USE IN SPECIFIC POPULATIONS

Pregnancy: Advise pregnant women that Enstilar Foam may increase the potential risk of having a low birth weight infant and to use Enstilar Foam on the smallest area of skin and for the shortest duration possible.

Lactation: No data are available regarding the presence of topically administered calcipotriene and betamethasone dipropionate in human milk. Use Enstilar Foam on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Enstilar Foam directly to the nipple and areola to avoid direct infant exposure.

Pediatric Use: The safety and effectiveness of Enstilar Foam in pediatric patients less than 12 years of age have not been established. Pediatric patients may be more susceptible to systemic toxicity, HPA axis suppression, and adrenal insufficiency due to their larger skin surface to body mass ratios.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more information, please see U.S. FDA Full Prescribing Information for Enstilar Foam.

(1)Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009; 60: 643-659.

(2)Psoriasis Statistics. National Psoriasis Foundation website. https://www.psoriasis.org/content/statistics. Accessed April 9, 2020.

(3)Lebwohl, Mark et al. Long-term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam; results of a Phase III randomized controlled trial. Featured at American Academy of Dermatology VMX. Poster #18223. June 12, 2020.

(4)Lebwohl, Mark et al. Safety of long-term proactive management with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam in patients with psoriasis vulgaris; results of a Phase III, multicenter, randomized, 52-week, vehicle-controlled trial. Featured at American Academy of Dermatology VMX. Poster #12797. June 12, 2020.

(5)Feldman, SR. et al. The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives. Am Health Drug Benefits. 2016;9(9);504-513.

(6)Plaque Psoriasis Fact Sheet. National Psoriasis Foundation website. https://www.psoriasis.org/sites/default/files/plaque_fact_sheet.pdf. Updated October 2017. Accessed April 9, 2020.