• ECZTRA 3 trial is the first Phase 3 trial evaluating a targeted anti-IL-13 biologic in combination with topical corticosteroid (TCS), which is reflective of clinical practice¹
• Results show maintained response with tralokinumab in ECZTRA 1, 2 and ECZTRA 3 over 52 weeks and 32 weeks, respectively. In ECZTRA 3, there was reduction in use of TCS in adult patients receiving tralokinumab plus TCS compared to placebo plus TCS^1,2
• First pivotal Phase 3 trials specifically targeting IL-13 alone with tralokinumab demonstrated safety comparable to placebo and efficacy over 52 weeks in ECZTRA 1 and 2, and over 32 weeks in ECZTRA 3 for treatment of atopic dermatitis in adults. This provides clinical evidence that IL-13 is a key cytokine in the pathogenesis of this disease^1,2

MADISON, N.J.–(BUSINESS WIRE)–LEO Pharma Inc., a global leader in medical dermatology, today announced that the British Journal of Dermatology has published primary data from the pivotal ECZTRA 1, 2 and ECZTRA 3 Phase 3 trials of tralokinumab in adult patients with moderate-to-severe atopic dermatitis (AD). Results demonstrate that treatment with tralokinumab with or without concomitant use of a TCS may provide sustained improvements in atopic dermatitis severity, and show improvements in itch, sleep interference and quality of life measures that are important to clinicians and patients.^1,2 To view the two published articles of the clinical trial data, please visit for ECZTRA 1/ECZTRA 2: https://onlinelibrary.wiley.com/doi/10.1111/bjd.19574 and for ECZTRA 3: https://onlinelibrary.wiley.com/doi/10.1111/bjd.19573.

(Read more…)

Tralokinumab is a fully human, high affinity monoclonal antibody that specifically neutralizes the IL-13 cytokine, a key driver of the underlying chronic inflammation in atopic dermatitis.^3,4 It is an investigational therapy under clinical development, and its efficacy and safety are currently being evaluated by regulatory authorities.

The ECZTRA 3 trial (n=380) – the first Phase 3 trial evaluating a targeted anti-IL-13 biologic in combination with topical corticosteroid (TCS) mometasone furoate 0.1% – demonstrated the clinical response of tralokinumab 300 mg every two weeks (Q2W) plus TCS in improvements in atopic dermatitis severity, quality of life and signs and symptoms.¹ Specifically, tralokinumab plus TCS as compared to placebo plus TCS demonstrated:¹

– Improvements in disease severity as assessed by primary endpoints of IGA 0/1 and EASI-75 at week 16

– Sustained improvements through week 32 in patients who were randomized to continue with two different dosing frequencies, Q2W or every four weeks (Q4W)

• 90% of responders (subjects who met primary IGA 0/1 and/or EASI-75 at week 16) maintained response at week 32 when randomized to continue tralokinumab Q2W plus TCS
• 80% of responders maintained response at week 32 when randomized to continue tralokinumab Q4W plus TCS

– Additional improvements included:

• Itch, as assessed by reduction in worst daily pruritus Numeric Rating Scale (NRS) (weekly average) ≥4, as early as week 2 with continued improvement to week 16
• Dermatology Life Quality Index (DLQI) scores by week 2, with continued improvement to week 16 and through week 32
• Patient-reported disease severity as assessed by the Patient-Oriented Eczema Measure (POEM) by week 2, with continued improvement to week 16
• Approximately 50% less TCS use at weeks 15-16 for those treated with tralokinumab vs placebo

“As clinicians, we always want more options for patients with atopic dermatitis,” explained Jonathan Silverberg, MD, PhD, MPH, Associate Professor of Dermatology at George Washington University School of Medicine and Health Sciences in Washington, DC. “I’m excited about the potential of a new treatment option like tralokinumab that targets IL-13, which is a key driver of the chronic inflammation of atopic dermatitis.”

Results from the ECZTRA 1 and 2 monotherapy trials (n=802 and 794, respectively) demonstrated safety and efficacy of tralokinumab 300 mg Q2W vs placebo with significant improvements in atopic dermatitis severity that were maintained up to 1 year for the majority of patients, without the need for rescue medication.² ECZTRA 1 and 2 show tralokinumab compared to placebo demonstrated:²

− Improvements in disease severity as assessed by primary endpoints IGA 0/1 and EASI-75 at week 16

− Additional improvements included:

• DLQI scores by week 2 with continued improvement to week 16
• Itch and sleep interference (assessed by eczema-related sleep interference NRS score) as early as week 1 with continued improvement to week 16
• More than 50% of patients who achieved clinical responses at week 16 with tralokinumab Q2W maintained that response through week 52 without any rescue medication, including TCS, and 39–51% of patients maintained response when receiving tralokinumab Q4W without any rescue medication

Across all three clinical trials, tralokinumab demonstrated a comparable safety profile vs placebo with regards to overall frequency and severity of AEs.^1,2 The most commonly reported AEs that were higher with tralokinumab than placebo included viral upper respiratory tract infections, conjunctivitis, headache, upper respiratory tract infection, and injection site reaction in ECZTRA 3, and upper respiratory tract infections and conjunctivitis in ECZTRA 1, 2.^1,2

“The secondary efficacy and patient-reported outcomes from the three Phase 3 trials provide additional evidence of the clinical response of tralokinumab and suggest that, if approved, tralokinumab may be considered a potential first-line targeted biologic treatment option for adults with moderate-to-severe atopic dermatitis whose disease is not controlled by topical therapies,” said Kim Kjoeller, M.D., Executive Vice President, Global Research & Development, LEO Pharma. “We remain committed to researching and developing new treatment options that address the significant and varied unmet needs of people living with skin inflammation diseases, like atopic dermatitis.”

LEO Pharma has submitted regulatory applications for tralokinumab to the European Medicines Agency and the U.S. Food and Drug Administration.

About the British Association of Dermatologists

The British Association of Dermatologists is the central association of practising UK dermatologists. Our aim is to continually improve the treatment and understanding of skin disease. For further information about the charity, visit www.bad.org.uk

Wiley is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. For more information, please visit www.wiley.com.

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 atopic dermatitis who were candidates for systemic therapy.^5,6

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 reduction 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.^5,6

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 atopic dermatitis who are candidates for systemic therapy.⁷

Patients with moderate-to-severe atopic dermatitis 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.⁷

About atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory, heterogeneous skin disease characterized by intense itch and eczematous lesions.⁸ Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.⁹ Type-2 cytokines including IL-13 play a central role in the key aspects of pathophysiology.^3,11 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.^10,11

About tralokinumab

Tralokinumab is a fully human, high affinity immunoglobulin (Ig) G4 monoclonal antibody (mAb) that works by neutralizing the IL-13 cytokine.⁴ IL-13 plays a key role in driving the underlying chronic inflammation in atopic dermatitis.^3,11 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.⁴

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

---

¹Silverberg JI, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. British Journal of Dermatology. 2020.

²Wollenberg, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). British Journal of Dermatology. 2020.

³Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75:54–62.

⁴Popovic 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.

⁵ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis – ECZTRA 1 (ECZema TRAlokinumab Trial no. 1). Identifier NCT03131648. https://clinicaltrials.gov/ct2/show/NCT03131648

⁶ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis – ECZTRA 2 (ECZema TRAlokinumab Trial no. 2). Identifier NCT03160885. https://www.clinicaltrials.gov/ct2/show/NCT03160885

⁷ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab in Combination With Topical Corticosteroids for Moderate to Severe Atopic Dermatitis – ECZTRA 3 (ECZema TRAlokinumab Trial no. 3). Identifier NCT03363854. https://clinicaltrials.gov/ct2/show/NCT03363854

⁸Weidinger S, et al. Atopic dermatitis. Lancet 2016;387:1109-1122.

⁹Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242(1):233-46.

¹⁰Sanyal 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.

¹¹Tsoi 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.

MAT-38833. October 2020.

Contacts

Linda Mayer

Global Product Communications

+1 973 908 7924

[email protected]

• ECZTRA 3 trial is the first Phase 3 trial evaluating a targeted anti-IL-13 biologic in combination with topical corticosteroid (TCS), which is reflective of clinical practice¹
• Results show maintained response with tralokinumab in ECZTRA 1, 2 and ECZTRA 3 over 52 weeks and 32 weeks, respectively. In ECZTRA 3, there was reduction in use of TCS in adult patients receiving tralokinumab plus TCS compared to placebo plus TCS^1,2
• First pivotal Phase 3 trials specifically targeting IL-13 alone with tralokinumab demonstrated safety comparable to placebo and efficacy over 52 weeks in ECZTRA 1 and 2, and over 32 weeks in ECZTRA 3 for treatment of atopic dermatitis in adults. This provides clinical evidence that IL-13 is a key cytokine in the pathogenesis of this disease^1,2

MADISON, N.J.–(BUSINESS WIRE)–LEO Pharma Inc., a global leader in medical dermatology, today announced that the British Journal of Dermatology has published primary data from the pivotal ECZTRA 1, 2 and ECZTRA 3 Phase 3 trials of tralokinumab in adult patients with moderate-to-severe atopic dermatitis (AD). Results demonstrate that treatment with tralokinumab with or without concomitant use of a TCS may provide sustained improvements in atopic dermatitis severity, and show improvements in itch, sleep interference and quality of life measures that are important to clinicians and patients.^1,2 To view the two published articles of the clinical trial data, please visit for ECZTRA 1/ECZTRA 2: https://onlinelibrary.wiley.com/doi/10.1111/bjd.19574 and for ECZTRA 3: https://onlinelibrary.wiley.com/doi/10.1111/bjd.19573.

(Read more…)

Tralokinumab is a fully human, high affinity monoclonal antibody that specifically neutralizes the IL-13 cytokine, a key driver of the underlying chronic inflammation in atopic dermatitis.^3,4 It is an investigational therapy under clinical development, and its efficacy and safety are currently being evaluated by regulatory authorities.

The ECZTRA 3 trial (n=380) – the first Phase 3 trial evaluating a targeted anti-IL-13 biologic in combination with topical corticosteroid (TCS) mometasone furoate 0.1% – demonstrated the clinical response of tralokinumab 300 mg every two weeks (Q2W) plus TCS in improvements in atopic dermatitis severity, quality of life and signs and symptoms.¹ Specifically, tralokinumab plus TCS as compared to placebo plus TCS demonstrated:¹

– Improvements in disease severity as assessed by primary endpoints of IGA 0/1 and EASI-75 at week 16

– Sustained improvements through week 32 in patients who were randomized to continue with two different dosing frequencies, Q2W or every four weeks (Q4W)

• 90% of responders (subjects who met primary IGA 0/1 and/or EASI-75 at week 16) maintained response at week 32 when randomized to continue tralokinumab Q2W plus TCS
• 80% of responders maintained response at week 32 when randomized to continue tralokinumab Q4W plus TCS

– Additional improvements included:

• Itch, as assessed by reduction in worst daily pruritus Numeric Rating Scale (NRS) (weekly average) ≥4, as early as week 2 with continued improvement to week 16
• Dermatology Life Quality Index (DLQI) scores by week 2, with continued improvement to week 16 and through week 32
• Patient-reported disease severity as assessed by the Patient-Oriented Eczema Measure (POEM) by week 2, with continued improvement to week 16
• Approximately 50% less TCS use at weeks 15-16 for those treated with tralokinumab vs placebo

“As clinicians, we always want more options for patients with atopic dermatitis,” explained Jonathan Silverberg, MD, PhD, MPH, Associate Professor of Dermatology at George Washington University School of Medicine and Health Sciences in Washington, DC. “I’m excited about the potential of a new treatment option like tralokinumab that targets IL-13, which is a key driver of the chronic inflammation of atopic dermatitis.”

Results from the ECZTRA 1 and 2 monotherapy trials (n=802 and 794, respectively) demonstrated safety and efficacy of tralokinumab 300 mg Q2W vs placebo with significant improvements in atopic dermatitis severity that were maintained up to 1 year for the majority of patients, without the need for rescue medication.² ECZTRA 1 and 2 show tralokinumab compared to placebo demonstrated:²

− Improvements in disease severity as assessed by primary endpoints IGA 0/1 and EASI-75 at week 16

− Additional improvements included:

• DLQI scores by week 2 with continued improvement to week 16
• Itch and sleep interference (assessed by eczema-related sleep interference NRS score) as early as week 1 with continued improvement to week 16
• More than 50% of patients who achieved clinical responses at week 16 with tralokinumab Q2W maintained that response through week 52 without any rescue medication, including TCS, and 39–51% of patients maintained response when receiving tralokinumab Q4W without any rescue medication

Across all three clinical trials, tralokinumab demonstrated a comparable safety profile vs placebo with regards to overall frequency and severity of AEs.^1,2 The most commonly reported AEs that were higher with tralokinumab than placebo included viral upper respiratory tract infections, conjunctivitis, headache, upper respiratory tract infection, and injection site reaction in ECZTRA 3, and upper respiratory tract infections and conjunctivitis in ECZTRA 1, 2.^1,2

“The secondary efficacy and patient-reported outcomes from the three Phase 3 trials provide additional evidence of the clinical response of tralokinumab and suggest that, if approved, tralokinumab may be considered a potential first-line targeted biologic treatment option for adults with moderate-to-severe atopic dermatitis whose disease is not controlled by topical therapies,” said Kim Kjoeller, M.D., Executive Vice President, Global Research & Development, LEO Pharma. “We remain committed to researching and developing new treatment options that address the significant and varied unmet needs of people living with skin inflammation diseases, like atopic dermatitis.”

LEO Pharma has submitted regulatory applications for tralokinumab to the European Medicines Agency and the U.S. Food and Drug Administration.

About the British Association of Dermatologists

The British Association of Dermatologists is the central association of practising UK dermatologists. Our aim is to continually improve the treatment and understanding of skin disease. For further information about the charity, visit www.bad.org.uk

Wiley is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. For more information, please visit www.wiley.com.

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 atopic dermatitis who were candidates for systemic therapy.^5,6

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 reduction 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.^5,6

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 atopic dermatitis who are candidates for systemic therapy.⁷

Patients with moderate-to-severe atopic dermatitis 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.⁷

About atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory, heterogeneous skin disease characterized by intense itch and eczematous lesions.⁸ Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.⁹ Type-2 cytokines including IL-13 play a central role in the key aspects of pathophysiology.^3,11 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.^10,11

About tralokinumab

Tralokinumab is a fully human, high affinity immunoglobulin (Ig) G4 monoclonal antibody (mAb) that works by neutralizing the IL-13 cytokine.⁴ IL-13 plays a key role in driving the underlying chronic inflammation in atopic dermatitis.^3,11 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.⁴

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

---

¹Silverberg JI, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. British Journal of Dermatology. 2020.

²Wollenberg, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). British Journal of Dermatology. 2020.

³Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75:54–62.

⁴Popovic 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.

⁵ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis – ECZTRA 1 (ECZema TRAlokinumab Trial no. 1). Identifier NCT03131648. https://clinicaltrials.gov/ct2/show/NCT03131648

⁶ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis – ECZTRA 2 (ECZema TRAlokinumab Trial no. 2). Identifier NCT03160885. https://www.clinicaltrials.gov/ct2/show/NCT03160885

⁷ClinicalTrials.gov. National Library of Medicine (U.S.). Tralokinumab in Combination With Topical Corticosteroids for Moderate to Severe Atopic Dermatitis – ECZTRA 3 (ECZema TRAlokinumab Trial no. 3). Identifier NCT03363854. https://clinicaltrials.gov/ct2/show/NCT03363854

⁸Weidinger S, et al. Atopic dermatitis. Lancet 2016;387:1109-1122.

⁹Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242(1):233-46.

¹⁰Sanyal 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.

¹¹Tsoi 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.

MAT-38833. October 2020.

Contacts

Linda Mayer

Global Product Communications

+1 973 908 7924

[email protected]