LEO Pharma Announces Positive Results From Phase 2b Clinical Study for Tralokinumab in Atopic Dermatitis

BALLERUP, Denmark and ORLANDO, FL, March 3, 2017 /CNW/ - LEO Pharma today announced positive results from a Phase 2b dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate to severe atopic dermatitis (AD), a serious and chronic form of eczema. Tralokinumab is an investigational monoclonal antibody that specifically targets the cytokine IL-13^[1],[2], which plays an important role in the development of moderate-to-severe AD^[3],[4]. In the Phase 2b study, tralokinumab demonstrated efficacy in the primary and key secondary endpoints, and an adverse event profile comparable to placebo. It also demonstrated significant improvements in quality of life and itching, compared with placebo.

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"These clinical results support that blocking IL-13 signalling is a promising new option for patients with atopic dermatitis," said Kim Kjoeller, Executive Vice President, Global Research and Development, LEO Pharma. "We are encouraged by these results and are planning to enter phase 3 of clinical development for tralokinumab in the first half of 2017."

An E-Poster presenting Phase 2b results will be available at the ongoing annual meeting of the American Academy of Dermatology (AAD) from Friday, 3 March 2017 (Poster #4496^[5]). An oral presentation of the poster will take place on Friday, 3/3/2017, from 3:00:00 PM EST to 3:05:00 PM in the Dermatitis, Atopic Section.

The double-blinded Phase 2b study included 204 adults who had moderate to severe AD despite a two week run-in with continuous mid-strength topical corticosteroids (TCS) treatment. Patients were randomized 1:1:1:1 to receive tralokinumab (45, 150, or 300 mg) or placebo by sub-cutaneous administration every second week for 12 weeks.

Overall objective of the study was to evaluate whether tralokinumab provides therapeutic benefit to adults with moderate to severe AD despite treatment with mid-strength TCS. Co-primary endpoints were change from baseline in Eczema Area Severity Index (EASI) and percentage of patients with clear or almost clear Investigator's Global Assessment (IGA 0/1) at week 12. Further efficacy endpoints, patient-reported outcomes, serum biomarkers and safety endpoints were assessed.

After treatment with tralokinumab for 12 weeks, 150 mg and 300 mg tralokinumab significantly reduced total EASI from baseline (adjusted mean difference of -4.4, p=0.027 and -4.9, p=0.011, respectively) compared with placebo. The number of patients achieving EASI 50 at week 12 in the tralokinumab 300 mg group was significantly higher compared with placebo (73.4% versus 51.9%, p=0.025).

The number of patients with an IGA of 0 or 1 (clear or almost clear) was numerically higher but not statistically significantly superior to placebo (26.5% in the tralokinumab 300 mg versus 11.7% in the placebo group). Treatment with Class 3 TCS before, during, and after study drug treatment may have influenced the study results.

The secondary endpoints showed significant reduction in Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) in the tralokinumab arm (150mg and 300 mg) compared with placebo. Furthermore, reduction in pruritus Numerical Rating Scale (NRS) in the tralokinumab 300 mg group was also found to be greater than placebo.

The most frequent adverse events in all groups (tralokinumab and placebo) were nasopharyngitis (~17%), upper respiratory tract infection (~9%), headache (~6%), and AD (~6%).^[5]

LEO Pharma is the world leader in topical psoriasis treatment and has significantly expanded its portfolio over recent years to cover several dermatology indications. In July 2016, LEO Pharma acquired the global licence to tralokinumab in skin diseases from AstraZeneca, as well as the exclusive licence to brodalumab in Europe. Brodalumab is an IL-17 receptor monoclonal antibody under regulatory review for patients with moderate-to-severe plaque psoriasis. In partnership with MorphoSys, LEO Pharma is now developing six biologic treatments for skin diseases.

About Atopic Dermatitis

AD is a serious and chronic form of eczema. It is the most common inflammatory skin disease with prevalence in western countries of 15-20% in children and 1-3% in adults^[6],[7]. The severity of AD can be categorized into mild, moderate and severe. The moderate and severe forms constitute approximately 50% and 20%, respectively, of the AD patient pool in a US population-based survey^[8]. AD is, in its moderate to severe form, a debilitating condition characterized by intense itching, painful skin lesions, and skin infections with significant impact on quality of life^[9]. There is currently a high unmet need for long-term efficacious and well-tolerated treatment options in AD^[10].

About LEO Pharma

LEO Pharma helps people achieve healthy skin. By offering care solutions to patients in more than 100 countries globally, LEO Pharma supports people in managing their skin conditions. Founded in 1908 and owned by the LEO Foundation, the healthcare company has devoted decades of research and development to delivering products and solutions to people with skin conditions. LEO Pharma is headquartered in Denmark and employs around 5,000 people worldwide.

References

1. May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH et al. Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma. Br J Pharmacol 2012;166(1):177-193.

2. Popovic B, Breed J, Rees DG, Gardener MJ, Vinall LM, Kemp B et al. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Ralpha1 and IL-13Ralpha2. J Mol Biol 2017;429(2):208-219.

3. Hamid Q, Naseer T, Minshall EM, Song YL, Boguniewicz M, Leung DY. In vivo expression of IL-12 and IL-13 in atopic dermatitis. J Allergy Clin Immunol 1996;98(1):225-231.

4. Brandt EB, Sivaprasad U. Th2 Cytokines and Atopic Dermatitis. J Clin Cell Immunol 2011;2(3).

5. Wollenberg A, Howell MD, Guttman E, Silverberg JI, Birrell C, Kell C et al. A Phase 2b Dose-Ranging Efficacy and Safety Study of Tralokinumab in Adult Patients with Moderate to Severe Atopic Dermatitis (AD). Poster #4496 for the 75th annual meeting of the American Academy of Dermatology, Orlando, FL. 2017

6. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol 2012;26(8):1045-1060.

7. Wollenberg A, Oranje A, Deleuran M, Simon D, Szalai Z, Kunz B et al. ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol 2016;30(5):729-747.

8. Hanifin JM, Reed ML. A population-based survey of eczema prevalence in the United States. Dermatitis 2007;18(2):82-91.

9. Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab 2015;66 Suppl 134-40.

10. Ask the Presenter - Q&A with Dr. Silverberg. AJMC 2016, Conference Report

SOURCE LEO Pharma A/S

Henrik Heskjaer Kyndlev, [email protected], Tel [phone]