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

PR67663

BALLERUP, Denmark and ORLANDO, Florida, Mar. 4, 2017 /PRNewswire=KYODO JBN/ --

     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.

(Logo: http://photos.prnewswire.com/prnh/20130221/595427 )

    "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.

     Contact     

Henrik Heskjaer Kyndlev     

henrik.kyndlev@leo-pharma.com     

Tel +45-3140-6180

     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