LEO Pharma Announces U.S. FDA Approval for Enstilar® (calcipotriene and betamethasone dipropionate) Foam U.S. Prescribing Information Update to Include Data in Long-term Use in Plaque Psoriasis Treatment

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-- U.S. Prescribing Information (USPI) updated to include PSO-LONG clinical trial data concerning long-term use (52 weeks) of twice-weekly topical treatment with Enstilar® (calcipotriene and betamethasone dipropionate) Foam in adults with plaque psoriasis --

-- Plaque psoriasis is a chronic, multifactorial disease affecting more than 80% of the 125 million people living with psoriasis worldwide1-3 --

LEO Pharma A/S today announced the U.S. Food and Drug Administration (FDA) has approved a U.S. Prescribing Information (USPI) update for Enstilar® (calcipotriene and betamethasone dipropionate) Foam to include data on long-term use in adults with plaque psoriasis.

Enstilar Foam is a combination of calcipotriene, a vitamin D analog, and betamethasone dipropionate, a corticosteroid, and is indicated in the U.S. for the topical treatment of plaque psoriasis in patients 12 years and older.

The U.S. supplemental New Drug Application (sNDA) submission was based on data from the Phase 3 PSO-LONG clinical trial. The randomized, double-blind, vehicle-controlled trial (NCT02899962) evaluated the long-term use of Enstilar Foam in adult patients who achieved treatment success, defined as Physician Global Assessment (PGA) score of "clear" or "almost clear" with at least a two-grade improvement from baseline, after an initial four-week treatment with once-daily Enstilar Foam.4

Participants (n=545) were randomized to receive Enstilar Foam or vehicle foam twice-weekly on two non-consecutive days for up to 52 additional weeks. Subjects experiencing a loss of response (defined as a PGA score of at least "mild") were treated once-daily with Enstilar Foam for four weeks, and those who regained a PGA score of "clear" or "almost clear" after four weeks then resumed randomized long-term use treatment.4

Those treated long-term twice-weekly with Enstilar Foam had a longer time to first loss of response and fewer losses of response than those using vehicle foam. Enstilar Foam met the primary endpoint in the PSO-LONG trial by prolonging time to first loss of response versus vehicle foam (56 days vs. 30 days; P<0.001).4

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 dipropionate foam, 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

"Data on long-term management of psoriasis with topical treatments are needed. To date, this is the first and only study to have reported on the long-term – up to 52 weeks (twice-weekly), after the initial four-week dosing period – efficacy and safety of calcipotriene and betamethasone dipropionate foam," said Mark Lebwohl*, M.D., Waldman Professor, Chairman of the Kimberly and Eric J. Waldman Department of Dermatology and Dean for Clinical Therapeutics, Icahn School of Medicine at Mount Sinai in New York City, and Principal Investigator for the PSO-LONG trial. "The results of this novel trial suggest that long-term twice-weekly use with fixed-dose Cal/BD foam could offer to help patients maintain clear or almost clear skin for up to 52 weeks."

Psoriasis is a chronic, multifactorial disease that primarily affects the skin.1 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.2,5 Topical treatments are often prescribed in mild-to-moderate cases of plaque psoriasis.1

"This USPI update to include data from the PSO-LONG clinical trial reflects new clinical insights concerning the long-term use of a twice-weekly topical treatment for plaque psoriasis," said Kim Kjoeller, M.D., Executive Vice President, Global Research and Development, LEO Pharma. "LEO Pharma is committed to advancing the standard of care for patients with skin diseases, where unmet needs and scientific advances are offering a great potential to bring new research forward."

Separately in September 2020, updates to the Summary of Product Characteristics (SmPC) for Enstilar Cutaneous Foam were approved in 30 European Economic Area countries, as appropriate in the European market, for treatment in adults with psoriasis vulgaris, via the Mutual Recognition Procedure; the Danish Health Authority served as the Reference Member State.

About the PSO-LONG Clinical Trial4
The 12-month, international, multi-center, randomized, vehicle-controlled, double-blind, two-arm, parallel group trial compared the safety and efficacy combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam with vehicle foam used twice weekly as [long-term use/maintenance treatment] in adults with psoriasis vulgaris (plaque psoriasis). Find additional information about the PSO-LONG trial at clinicaltrials.gov.

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

About Psoriasis
Psoriasis is a chronic, systemic inflammatory disease that primarily affects the skin in 125 million people worldwide.1,3 About 80% to 90% of patients are affected by plaque psoriasis, the most common clinical form of psoriasis.2 The symptoms of plaque psoriasis are itchy or painful raised scaly and inflamed plaques. Plaques may appear anywhere on the body, but often appear on the scalp, knees, elbows and torso.2 The National Psoriasis Foundation defines mild psoriasis as affecting less than 3% of the body; 3% to 10% is considered moderate; more than 10% is considered severe.3

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 following application.

  • Hypercalcemia and Hypercalciuria: Hypercalcemia and hypercalciuria have been reported. If either occurs, discontinue until parameters of calcium metabolism normalize.

  • Effects on Endocrine System: Can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency during and 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 with topical calcipotriene and topical corticosteroids.

  • Ophthalmic Adverse Reactions: May increase the risk of posterior subcapsular cataracts 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 for evaluation.

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.

About LEO Pharma
LEO Pharma is a leader in medical dermatology with a robust R&D pipeline, a wide range of therapies and a pioneering spirit. Founded in 1908 and owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, setting new standards of care for people with skin conditions. LEO Pharma is headquartered in Denmark with a global team of 6,000 people, serving 92 million patients in 130 countries. In 2019, the company generated net sales of USD 1,622 million. For more information please visit: www.leo-pharma.com.

MAT-37598. October 2020.

References
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 Plaque Psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/plaque/. Updated September 2020. Accessed Sept. 28, 2020.
3 Psoriasis Statistics. National Psoriasis Foundation website . https://www.psoriasis.org/content/statistics. Accessed April 9, 2020.
4 Lebwohl M, Kircik L, Lacour J-P, Liljedahl M, Lynde C, Mørch MH, Papp KA, Perrot J-L, Gold LS, Takhar A, Thaçi D, Warren RB, Wollenberg A, Twice-weekly topical calcipotriene / betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial), Journal of the American Academy of Dermatology (2020), doi: https://doi.org/10.1016/j.jaad.2020.09.037.
5 About Psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/about-psoriasis/. Updated September 2020. Accessed Sept. 28, 2020.

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