BALLERUP, Denmark--(BUSINESS WIRE) June 12, 2020 --LEO Pharma A/S, a global leader in medical dermatology, today announced results that tralokinumab 300 mg, administered subcutaneously every two weeks, demonstrated efficacy and safety with or without concomitant use of a topical corticosteroid (TCS) in three Phase 3 trials (ECZTRA 1-3) for the treatment of adults with moderate-to-severe atopic dermatitis (AD). Results were presented online at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2020.3,4

Tralokinumab is an investigational therapy under clinical development, and its efficacy and safety have not been evaluated by any regulatory authority. Tralokinumab is a fully human monoclonal antibody that specifically neutralizes the IL-13 cytokine, a key driver of the underlying chronic inflammation in AD.1,2

In all three trials, tralokinumab met its primary endpoints at week 16 as assessed by the Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75). Tralokinumab also demonstrated significant improvements in secondary endpoints, including the extent and severity of skin lesions, pruritus (itch) and health-related quality of life measures at week 16, when administered once every two weeks with or without concomitant TCS use. Secondary endpoints assessing AD signs and symptoms were measured by changes in the following scores: SCORing Atopic Dermatitis (SCORAD), Pruritus Numeric Rating Scale (NRS) and Dermatology Life Quality Index (DLQI).3,4

In the ECZTRA 1 and 2 monotherapy trials, the majority of patients treated with tralokinumab 300 mg every two weeks who achieved a clinical response at week 16 (IGA 0/1 or EASI-75), maintained response at week 52 without any use of TCS.3

In the ECZTRA 3 combination trial, significantly more patients treated with tralokinumab plus TCS achieved IGA 0/1 (39%) and/or EASI-75 (56%) at week 16 as compared with patients treated with placebo plus TCS (26% and 36%; p=0.015 and p<0.001 for IGA 0/1 and EASI-75 respectively).4

In addition, the majority of patients who responded at week 16 maintained response at week 32 when continuing with two different dosing frequencies of tralokinumab. Nine out of 10 patients randomized to continue with tralokinumab every two-week dosing plus a TCS maintained clear or almost clear skin at week 32, while eight out of 10 patients randomized to continue with once every four-week dosing plus a TCS maintained clear or almost clear skin at week 32.3,4

Tralokinumab demonstrated a safety profile comparable to placebo over 52 weeks with regard to the overall frequency and severity of adverse events (AEs).3,4

“Given the serious physical, social and emotional impact of moderate-to-severe AD, there is a critical need for additional treatment options for patients,” said Eric Simpson, M.D., lead clinical investigator for the ECZTRA 2 study and Professor of Dermatology at the Oregon Health & Science University. “These results are the first Phase 3 results to be presented in AD for a biologic that specifically targets IL-13 alone, which is suggested to be a primary effector cytokine driving inflammation in AD skin.”

“We are encouraged that nine out of 10 patients who achieved the defined clinical response at week 16 maintained response at week 32 when tralokinumab was administered every two weeks in combination with a TCS. Additionally, in patients responding to tralokinumab every two weeks as a monotherapy at week 16, the majority maintained response at week 52 without any use of TCS,” said Kim Kjoeller, M.D., Executive Vice President, Global Research & Development, LEO Pharma. “LEO Pharma’s heritage in medical dermatology and strategic focus on advancing the science of skin inflammation diseases uniquely positions us to address the significant and varied unmet needs of people living with AD.”

ECZTRA 1 and 2 Monotherapy Results (n=802 and 794, respectively)3

Efficacy

• At week 16, IGA 0/1 responses were 16% (tralokinumab) vs. 7% (placebo; p=0.002) and 22% vs. 11% (p<0.001) in ECZTRA 1 and 2, respectively.
• At week 16, EASI-75 response was 25% (tralokinumab) vs. 13% (placebo; p<0.001) and 33% vs. 11% (p<0.001) in ECZTRA 1 and 2, respectively.
• At 52 weeks, 51% and 59% of patients who responded at week 16 maintained IGA 0/1 response with tralokinumab every two weeks in ECZTRA 1 and 2, respectively. The maintained responses in patients randomized to tralokinumab every four weeks were 39% and 45% in ECZTRA 1 and 2, respectively.
• At 52 weeks, 60% and 56% of patients who responded at week 16 maintained EASI-75 response with tralokinumab every two weeks in ECZTRA 1 and 2, respectively. The maintained responses in patients randomized to tralokinumab every four weeks were 49% and 51% in ECZTRA 1 and 2, respectively.

Safety

ECZTRA 1: The overall frequency (76% for tralokinumab and 77% for placebo) and severity of AEs in ECZTRA 1 were comparable across the treatment groups over 16 weeks. The AE profile over 52 weeks was comparable to the initial 16 weeks.

• The most commonly reported AEs that were higher with tralokinumab included viral upper respiratory tract infections (23% tralokinumab; 21% placebo) and conjunctivitis (7% tralokinumab; 2% placebo).

ECZTRA 2: The overall frequency (62% for tralokinumab and 66% for placebo) and severity of AEs in ECZTRA 2 were comparable across the treatment groups over 16 weeks. The AE profile over 52 weeks was comparable to the initial 16 weeks.

• The most commonly reported AEs that were higher with tralokinumab included upper respiratory tract infections (10% tralokinumab; 9% placebo) and conjunctivitis (3% tralokinumab; 2% placebo).

ECZTRA 3 TCS Combination Therapy Results (n=380)4

Efficacy

• At week 16, significantly more patients treated with tralokinumab plus TCS achieved IGA 0/1 (39%) and EASI-75 (56%) than placebo plus patients treated with TCS (26% and 36%; p=0.015 and p<0.001).
• 90% and 93% (IGA 0/1 and EASI-75, respectively) of patients who responded at week 16 maintained response at week 32 with tralokinumab administered 300 mg every two weeks in combination with TCS.
• 78% and 91% (IGA 0/1 and EASI-75, respectively) of patients who responded at week 16 (with tralokinumab plus TCS administered 300 mg every two weeks for those 16 weeks) maintained response at week 32 when switched to tralokinumab administered 300 mg every four weeks in combination with TCS.

Safety

ECZTRA 3: The overall frequency (71% for tralokinumab plus TCS and 67% for placebo plus TCS) and severity of AEs were comparable across the treatment groups over 16 weeks. The AE profile over 32 weeks was comparable to the initial 16 weeks.

• The most commonly reported AEs that were higher with tralokinumab plus TCS included viral upper respiratory tract infections (19% tralokinumab plus TCS; 11% placebo plus TCS), conjunctivitis (11% tralokinumab plus TCS; 3% placebo plus TCS), headache (9% tralokinumab plus TCS; 5% placebo plus TCS), upper respiratory tract infections (8% tralokinumab plus TCS; 5% placebo plus TCS) and injection site reactions (7% tralokinumab plus TCS; 0.0% placebo plus TCS).
• For AEs of particular interest, tralokinumab plus TCS was associated with lower rates of severe and serious infections and eczema herpeticum versus placebo plus TCS.

About ECZTRA 1, 2 and 3

ECZTRA 1 and ECZTRA 2 (ECZema TRAlokinumab trials Nos. 1 and 2) were randomized, double-blind, placebo-controlled, multinational 52-week trials, which included 802 and 794 adult patients, respectively, to evaluate the efficacy and safety of tralokinumab (300 mg) as monotherapy in adults with moderate-to-severe AD who were candidates for systemic therapy.

In both trials, following a washout period, patients were randomized to subcutaneous tralokinumab 300 mg or placebo every two weeks for 16 weeks. Tralokinumab dosing was started with a 600 mg loading dose on day 0. At week 16, patients who responded to tralokinumab with an IGA score of 0/1 and/or EASI score change of at least 75% from baseline were re-randomized to tralokinumab every other week (Q2W) or every four weeks (Q4W), or placebo for an additional 36 weeks. Patients who responded to placebo at week 16 continued on placebo in order to maintain blinding, but they were not re-randomized or included in the efficacy analyses. All patients who did not respond to study criteria received open-label tralokinumab Q2W with optional TCS.

ECZTRA 3 was a double-blind, randomized, placebo-controlled, multinational 32-week study, which included 380 adult patients, to evaluate the efficacy and safety of tralokinumab (300 mg) in combination with TCS in adults with moderate-to-severe AD who are candidates for systemic therapy.

Patients with moderate-to-severe AD were, following a washout period, randomized to subcutaneous tralokinumab 300 mg Q2W plus TCS or control (placebo (Q2W) plus TCS). Tralokinumab dosing was started with a 600 mg loading dose on day 0. At week 16, patients who responded to tralokinumab (IGA 0/1 and/or EASI-75) were re-randomized to tralokinumab Q2W plus TCS or Q4W plus TCS for an additional 16 weeks. Patients who responded to placebo plus TCS at week 16 continued that treatment to maintain the blinding of the study but they were not re-randomized or included in the efficacy analyses. All patients who did not respond to study criteria received tralokinumab Q2W plus TCS.4

About Atopic Dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory, heterogeneous skin disease characterized by intense itch and eczematous lesions.5 AD is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.6 Type-2 cytokines, such as IL-13 and IL-4, play a central role in the key aspects of AD pathophysiology.1 Due to the immune dysregulation, IL-13 is overexpressed in lesional and non-lesional skin and the level of IL-13 expression in lesional skin correlates with AD severity.7,8

About Tralokinumab

Tralokinumab is a fully human, immunoglobulin (Ig) G4 monoclonal antibody (mAb) that works by neutralizing the IL-13 cytokine.1,2 IL-13 plays a key role in driving the underlying chronic inflammation in AD.1,8 By specifically binding to the IL-13 cytokine with high affinity, tralokinumab prevents its interaction with the receptor and the subsequent downstream IL-13 signalling.1,2

About LEO Pharma

The company 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. For more information about LEO Pharma, visit www.leo-pharma.com.

References

1 Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75:54–62.

2 Popovic B, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429:208-219.

3 Simpson E, et al. Efficacy and safety of tralokinumab monotherapy in adult patients with moderate-to-severe atopic dermatitis: Results from two 52-week Phase 3 trials (ECZTRA 1 and ECZTRA 2). Featured at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX); June 12, 2020.

4 Weidinger S, et al. Efficacy and safety of tralokinumab with concomitant topical corticosteroid in adult patients with moderate-to-severe atopic dermatitis: Results from the 32-week Phase 3 ECZTRA 3 trial. Featured at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX); June 12, 2020.

5 Weidinger S, et al. Atopic dermatitis. Lancet 2016;387:1109-1122.

6 Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242(1):233-46.

7 Sanyal RD, et al. Atopic dermatitis in African American patients is TH2/TH22-skewed withTH1/TH17 attenuation. Ann of Allergy Asthma Immunol. 2019;122:99-110.e6.

8 Tsoi LC, et al. Atopic dermatitis is an IL-13 dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol 2019;139:1480-1489.

Source: LEO Pharma

Posted: June 2020