LEO Pharma Submits BLA for Tralokinumab, the First Potential IL-13-Targeting Biologic to Challenge Dupixent in Moderate-to-Severe Atopic Dermatitis

July 11, 2020 News /BioValleyBIOON/ -- Danish pharmaceutical company LEO Pharma recently announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for tralokinumab, a drug intended for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD).FDAThe formal review of this BLA has been initiated, with a Prescription Drug User Fee Act (PDUFA) target date set for the second quarter of 2021. In June of this year, the European Medicines Agency (EMA) also accepted the marketing authorization application (MAA) for tralokinumab for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD), and its Committee for Medicinal Products for Human Use (CHMP) is currently conducting a regulatory review of this MAA.

If approved, tralokinumab will become the first biologic to challenge Sanofi/Regeneron’s Dupixent (dupilumab), which is currently the leading product and the only biologic in the field of atopic dermatitis (AD) treatment.

Atopic Dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczema. AD results from skin barrier dysfunction and immune dysregulation leading to chronic inflammation. Type 2 cytokines, including interleukin-13 (IL-13), play a central role in key aspects of the pathophysiology of AD.

Tralokinumab is a fully human IgG4 monoclonal antibody that exerts its effect by potently and specifically neutralizing interleukin-13 (IL-13). IL-13 is a key cytokine that plays a critical role in driving the intrinsic inflammation of atopic dermatitis. By binding to IL-13 with high affinity and specificity, tralokinumab blocks the interaction between IL-13 and its receptors, as well as subsequent downstream IL-13 signaling.

Tralokinumab is from LEO PharmaAstraZenecaAuthorization obtained. In July 2016, the two parties reached a $1 billion agreement under which AstraZeneca licensed two dermatology assets (tralokinumab and brodalumab) to LEO Pharma. Through this divestiture, AstraZeneca aimed to further focus its business scope on three core therapeutic areas—Tumor, Respiratory, Cardiovascular & Renal and Metabolism. Among the two antibody drugs acquired through this licensing agreement, brodalumab was approved by the European Union in July 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis.

In recent years, LEO Pharma has continued to strengthen its presence in the field of dermatology. In 2019, the company expanded its collaboration with Elektrofi to leverage the latter’s particle suspension formulation technology (Elektroject™) for developing innovative delivery methods for dermatological antibody drugs, enabling the administration of high-dose antibody therapies in a relatively small volume within seconds. Furthermore, the company completed the acquisitionBayerprescription dermatology business.

In late 2019, LEO Pharma further expanded its collaboration with HitGen by exercising options to license certain assets from HitGen.Small-molecule compounds, these compounds were identified by HitGen through screening of its proprietary DNA-encoded library (DEL) against an undisclosed dermatological target provided by LEO Pharma. As the project progresses, HitGen is eligible to receive relevant preclinical and clinical milestone payments and royalties.

Atopic Dermatitis (Image source: icresearch.net)

The submission of the tralokinumab Biologics License Application (BLA) is based on data from three pivotal Phase III studies (ECZTRA 1, 2, and 3). The first two were randomized, double-blind, placebo-controlled, multinational 52-week studies that enrolled 802 and 794 patients, respectively, to evaluate the efficacy and safety of tralokinumab (300 mg, subcutaneous injection) in adults with moderate-to-severe atopic dermatitis (AD). The third was a double-blind, randomized, placebo-controlled, multinational 32-week study assessing the efficacy and safety of tralokinumab (300 mg, subcutaneous injection) in combination with topical corticosteroids (TCS) in adults with moderate-to-severe AD.

The results showed that all three studies met all primary and secondary endpoints. The primary endpoints included: Investigator’s Global Assessment (IGA) of clear skin (IGA score of 0) or almost clear skin (IGA score of 1) at Week 16 of treatment, and ≥75% improvement in the Eczema Area and Severity Index (EASI) score from baseline at Week 16. Secondary endpoints included changes from baseline to Week 16 in the Scoring Atopic Dermatitis (SCORAD) index, Itch Numerical Rating Scale (NRS) score (≥4), and Dermatology Life Quality Index (DLQI). The overall incidence of adverse events was comparable between tralokinumab and placebo. These findings indicate that tralokinumab is an effective and well-tolerated long-term treatment option for adults with moderate-to-severe atopic dermatitis (AD).

Kim Kjøller, M.D., Executive Vice President of Global Research and Development at LEO Pharma, stated, “There is a significant unmet medical need among patients with moderate-to-severe atopic dermatitis that remains uncontrolled. If approved, tralokinumab will become the first biologic agent specifically designed to neutralize the IL-13 cytokine, and most importantly, it offers a more targeted treatment option for adults suffering from this debilitating disease. We will continue to collaborate with regulatory authorities in Europe and the United States to bring this innovative therapy to patients as soon as possible.” (Bioon.com)

Original Source:LEO Pharma announces U.S. Food and Drug Administration (FDA) acceptance of Biologics License Application (BLA) for tralokinumab for the treatment of adults with moderate-to-severe atopic dermatitis