New Phase 3 Data from LEO Pharma’s Dermatology Portfolio

UK PRESS RELEASE

 

FOR UK medical and healthcare trade media only – not for consumer media

 

EMBARGOED UNTIL: JUNE 12, 2020 AT  20:00 GMT

 

Tralokinumab achieves primary and secondary endpoints in three pivotal Phase 3 trials in adult patients with moderate-to-severe atopic dermatitis

 

-- Presented at the 2020 American Academy of Dermatology Annual Meeting, results from ECZTRA 1, 2 and 3 trials confirm tralokinumab met its primary and secondary endpoints and are the first Phase 3 results in atopic dermatitis for an investigational therapy that specifically targets IL-13 --

 

-- Tralokinumab demonstrated improvements in outcomes including pruritus (itch) and health-related quality of life measures that are important to patients --

-- In ECZTRA 1 and 2, more than half of patients treated with tralokinumab 300 mg every two weeks who achieved reduced symptoms at week 16, maintained response at week 52 without any use of topical corticosteroids --

 

-- In ECZTRA 3, nine out of 10 patients who achieved clear or almost clear skin with tralokinumab 300 mg in combination with topical corticosteroids at week 16 maintained this response at week 32 when randomized to dosing every two weeks. Similarly, eight out of 10 patients randomized to dosing every four weeks at week 16 maintained clear or almost clear skin at week 32 --

 

Hurley, Berks, UK, JUNE 12, 2020 – LEO Pharma A/S, a global leader in medical dermatology, today announced results that its investigational medicine tralokinumab 300 mg, administered subcutaneously every two weeks, demonstrated to be both efficacious and have a profile and severity of adverse events (AEs) similar to/comparable to the placebo group with or without concomitant use of a topical corticosteroid (TCS). The three Phase 3 trials, (ECZTRA 1-3) for the treatment of adults with moderate-to-severe atopic dermatitis (AD), were presented online at the 78^th Annual Meeting of the American Academy of Dermatology (AAD).^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 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.^1,2

 

Dr Andrew Pink, Consultant Dermatologist and Clinical Trials Lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London said “Atopic dermatitis (eczema) can have a serious impact on the physical, social and psychological wellbeing of those living with the condition and we need more treatment options. These Phase 3 results in atopic dermatitis are the first to be presented for a biologic that specifically targets IL-13 alone, a primary effector cytokine that drives skin inflammation, and could greatly impact how we treat atopic dermatitis in the future.”

 

In the ECZTRA 1 and 2 monotherapy trials, more than half of the 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.¹

 

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).²

 

In addition, the majority of patients who responded at week 16 and were then randomised maintained response at week 32 when continuing with two different dosing frequencies of tralokinumab. Nine out of 10 patients who responded at week 16 and were then randomised to continue with tralokinumab every two-week dosing plus TCS maintained clear or almost clear skin at week 32, while eight out of 10 patients who responded at week 16 and were then randomised to continue with once every four-week dosing plus TCS maintained clear or almost clear skin at week 32.^1,2

 

“It’s so vitally important that we develop new effective treatments for people living with atopic dermatitis”, said Andrew Proctor, Chief Executive of the UK patient charity National Eczema Society. “Doing even simple everyday things like having a shower and getting dressed can be agony when your skin is inflamed, cracked and bleeding. Many people are suffering because, for some patients, current eczema treatments don’t work well enough to control their symptoms.” 

 

“Tralokinumab specifically neutralizes the IL-13 cytokine and so works in a different way to current eczema treatments”, continued Proctor. “That’s what makes these research findings so exciting. Tralokinumab has been shown, in some patients, to reduce itch and calm episodic flare-ups, which many patients desperately need to manage this episodic condition and achieve an improved quality of life.”

 

Amit Aggarwal, Medical Director, LEO Pharma, Cluster North Europe, AU & NZ, said “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.”

 

Tralokinumab is 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.^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).^1,2

 

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

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)²

Efficacy

• At week 16, significantly more patients treated with tralokinumab plus TCS achieved IGA 0/1 (39%) and EASI-75 (56%) than placebo plus 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.

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.

 

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.³ 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.^3,4  IL-13 plays a key role in driving the underlying chronic inflammation in AD.³ 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. ^3,4  

 

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:

• Website: www.leo-pharma.co.uk
• Twitter: @LEOPharmaUKIE
• Instagram: @leopharmaukie
• Facebook: Facebook.com/LEOPharmaUKIE 
• QualityCare™: psoriasis.qualitycarebyleo.com

 

Contacts

 

Virgo Health

Dan Bullock

Account Manager

020 3900 6068

leoukvirgoteam@virgohealth.com

 

LEO Pharma

Julie Wong

Head of Communications, Europe North, AU & NZ

07825918989

JWGUK@leo-pharma.com

 

 

References

1. 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
2. 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.
3. Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75:54–62.
4. 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.
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.

 

 

UK MAT-35286 JUNE 2020

 

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EMBARGOED UNTIL 8 P.M. BST JUNE 12, 2020

 

LEO Pharma presents results from PSO-LONG study of twice-weekly Enstilar^® (calcipotriol and betamethasone dipropionate) cutaneous foam for topical use in long term maintenance treatment of plaque psoriasis

 

-- New results from the PSO-LONG clinical trial are the first to provide long term maintenance data for plaque psoriasis with twice-weekly topical treatment Enstilar^® (calcipotriol and betamethasone dipropionate) cutaneous foam --

-- Plaque psoriasis is a chronic, multifactorial disease affecting 90% of the nearly 2 million people living with psoriasis in the UK^1,2  --

 

-- LEO Pharma is committed to building on its more than 30-year heritage of developing treatments for people living with psoriasis and other chronic skin conditions --

BERKSHIRE, England, JUNE 12, 2020 – LEO Pharma A/S, a global leader in medical dermatology, today presented results from the Phase 3 PSO-LONG clinical trial. PSO-LONG compared the efficacy and safety of twice-weekly calcipotriol and betamethasone dipropionate cutaneous foam, versus foam vehicle for long term (52-week) maintenance treatment for adult patients with plaque psoriasis.^3,4 Results were presented as ePosters online at the American Academy of Dermatology (AAD) Virtual Meeting Experience (VMX) 2020.

 

Calcipotriol and betamethasone dipropionate cutaneous foam met the primary endpoint in the PSO-LONG trial by prolonging time to first relapse versus foam vehicle (56 days vs. 30 days) – the number of days until 50% of patients experienced first relapse.^3,4   

“The year-long, first of its kind PSO-LONG study provides new data for the long term maintenance treatment of adults with plaque psoriasis,” said Professor Warren, Consultant Dermatologist of Salford Royal NHS Foundation Trust and the University of Manchester. “The data shows that calcipotriol and betamethasone dipropionate cutaneous foam met the trial’s primary endpoint, both reducing relapses and increasing the number of relapse-free days compared to foam vehicle. This is positive news for both clinicians and patients when considering management regimens for psoriasis due to it being a chronic condition that people typically live with for many years, if not decades. More long term treatment options are essential for optimal outcomes.”

Psoriasis is a chronic, multifactorial disease that primarily affects the skin and often requires long term treatment.⁵ Plaque psoriasis is the most common type of psoriasis, characterised by an overactive immune system that causes inflammation of the skin and speeds up skin cell growth, which leads to plaque development.^1,5 Topical treatments are often prescribed in mild-to-moderate cases of plaque psoriasis.¹

 

“Our vision in psoriasis is to continue to enhance the range of prescription solutions that we provide for patients with all severities of psoriasis by continual development of our portfolio such as we have done here with the PSO-LONG study,” said Amit Aggarwal, Medical Director UK/IE, LEO Pharma. “Our diverse pipeline of innovative late-stage drug candidates aims to support a range of treatment options for clinicians and people living with psoriasis and other chronic skin conditions across the globe.”

 

Use of twice-weekly calcipotriol and betamethasone dipropionate cutaneous foam as a long term maintenance treatment is investigational and is not approved in any country, and safety and efficacy are currently being evaluated by regulatory authorities.

Safety was evaluated as effects on calcium homeostasis and on hypothalamic-pituitary-adrenal (HPA) axis with long term use of twice-weekly calcipotriol and betamethasone dipropionate cutaneous foam, among other safety assessments. No clinically relevant effects on calcium metabolism or the HPA axis were observed. Overall the safety profile was comparable across treatment groups.⁴

 

The virtual AAD Annual Meeting featured three ePosters highlighting efficacy, safety and open label data from the Phase 3 PSO-LONG trial:

• Long term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriol 0.005% and betamethasone dipropionate 0.064% cutaneous foam: results of a Phase III randomized controlled trial
• Safety of long term proactive management with fixed-dose combination calcipotriol 0.005% and betamethasone dipropionate 0.064% cutaneous foam in patients with psoriasis vulgaris: results of a Phase III, multicentre, randomized, 52-week, vehicle-controlled trial
• Results from the open-label treatment period of a long term proactive management phase III trial using fixed-dose combination calcipotriol 0.005% and betamethasone dipropionate 0.064% cutaneous foam

 

About PSO-LONG: Trial Design and Outcomes^3,4

The PSO-LONG trial (NCT02899962) is a 12-month, international, multi-centre, randomized, vehicle-controlled, double-blind, two-arm, parallel group trial comparing the safety and efficacy combination calcipotriol 0.005% and betamethasone dipropionate 0.064% cutaneous foam with foam vehicle used twice weekly as long term maintenance treatment in adults with psoriasis vulgaris (plaque psoriasis).

In the trial:

• 650 patients aged 18 or older were included in a four-week open label phase where each received once-daily calcipotriol and betamethasone dipropionate cutaneous foam.
• 521 patients (80%) achieved treatment success (Physician Global Assessment [PGA] “clear”/ “almost clear” with a minimum two-grade improvement from baseline) and were then randomized 1:1 to twice-weekly administration of either calcipotriol and betamethasone dipropionate cutaneous foam or vehicle foam for 52 weeks.
• In both arms, patients with relapse received once-daily calcipotriol and betamethasone dipropionate cutaneous foam for four weeks.
• 82% of patients had a PGA score of ‘moderate’ at baseline. 
• 251 randomized patients (46%) completed the long term study.

 

Eligibility requirements:

To have participated in the trial, patients must have:

• Been 18 years of age or older.
• Truncal and/or limb psoriasis involving 2-30% of body surface area, and
• PGA greater than or equal to mild and modified psoriasis area, and a severity index score (mPASI) of greater than or equal to two at first visit.

 

Results:

• The median time to first relapse was 56 days for calcipotriol and betamethasone cutaneous dipropionate foam vs. 30 days for foam vehicle – the number of days until 50% of patients experienced first relapse^3,4
• Risk of first relapse was 43% lower with calcipotriol and betamethasone dipropionate cutaneous foam vs. foam vehicle (HR, 0.57; 95% CI, 0.47-0.69; p<0.001).⁶

• At 12 months, the absolute risk reduction (first relapse) using proactive treatment was 7.5%.⁶

• Rate of relapse over one year was 46% lower for the calcipotriol and betamethasone cutaneous dipropionate foam group vs. the foam vehicle group (95% CI, 0.37-0.54; p<0.001).  The mean number of relapses for calcipotriol and betamethasone dipropionate foam (2.0) versus vehicle (3.1)⁶

• Rate of serious AEs per 100 patient-years was comparable (8.3, calcipotriol and betamethasone dipropionate cutaneous foam [n=272]; 7.9 foam vehicle [n=273]), as was rate of treatment-related AEs (2.8, calcipotriol and betamethasone dipropionate cutaneous foam [n=272]; 4.5 foam vehicle [n=273]).⁴

 

Find additional information about the PSO-LONG trial at clinicaltrials.gov.

 

About Psoriasis
Psoriasis is a chronic, systemic inflammatory disease that primarily affects the skin in 125 million people worldwide and nearly 2 million people in the UK. About 80% of patients are affected by plaque psoriasis, the most common clinical form of psoriasis.^1,2,7 The symptoms of plaque psoriasis are itchy or painful, scaly, inflamed plaques. Plaques may appear anywhere on the body, but often appear on the scalp, knees, elbows and torso. Psoriasis is characterized as mild when less than 3% of the body is affected and moderate to severe when more than 3% of the body is affected.⁶ Topical treatments are often prescribed in mild-to-moderate cases of plaque psoriasis.¹

 

About Enstilar^® (calcipotriol and betamethasone dipropionate) cutaneous foam
Enstilar cutaneous foam is a combination of calcipotriol, a vitamin D analog, and betamethasone dipropionate, a corticosteroid.

About LEO Pharma
LEO Pharma is a global organisation with a rich history and heritage of over 110 years expertise in developing innovative care solutions and holistic programmes.

 

We drive dermatology beyond the skin: We are ambitious and passionate about improving the lives of people that live with dermatological (skin) and thrombotic (blood clot) conditions. It is our ambition to have the broadest and deepest dermatology portfolio within the industry.

 

We are wholly owned by the LEO Foundation, which means that we have the privilege and obligation to always put patients first and not shareholders. We focus on patients' needs and do what is right in the long term to proudly serve patients rather than shareholders. Our Foundation model means we’re able to forego short-term profits and are free to invest in tomorrow's care solutions. This encourages long term research and development programmes.

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:

• Website: www.leo-pharma.co.uk
• Twitter: @LEOPharmaUKIE
• Instagram: @leopharmaukie
• Facebook: Facebook.com/LEOPharmaUKIE 
• QualityCare™: psoriasis.qualitycarebyleo.com

 

Contacts

Virgo Health UK

Dan Bullock

Account Manager

020 3900 6068

leoukvirgoteam@virgohealth.com

 

LEO Pharma

Alexandra Orton
Communications Manager UK/IE
07767277474

AAOUK@leo-pharma.com

LEO Pharma

Julie Wong
Head of Communications, Europe North, AU & NZ
07825918989

JWGUK@leo-pharma.com

References

 

1. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009; 60: 643-659
2. Mental Health Foundation, Psoriasis Association. 2012. See psoriasis:look deeper. Recognising the life impact of psoriasis. Available at https://www.mentalhealth.org.uk/sites/default/files/see-psoriasis.pdf. Acessed May 3, 2020
3. Lebwohl, Mark et al. Long-term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam; results of a Phase III randomized controlled trial. Featured at American Academy of Dermatology VMX. Poster #18223. June 12, 2020.
4. Lebwohl, Mark et al. Safety of long-term proactive management with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam in patients with psoriasis vulgaris; results of a Phase III, multicenter, randomized, 52-week, vehicle-controlled trial. Featured at American Academy of Dermatology VMX. Poster #12797. June 12, 2020.
5. Feldman, SR. et al. The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives. Am Health Drug Benefits. 2016;9(9);504-513.
6. Data on file - LEO90100 – June 10, 2020
7. Psoriasis Statistics. National Psoriasis Foundation website. https://www.psoriasis.org/content/statistics. Accessed May 3, 2020

UK IE MAT-35283 12 June 2020