Results presented at EADV by LEO Pharma show delgocitinib met primary and secondary end points in Phase 2b dose-finding study in mild-to-severe chronic hand eczema and reinforce the safety profile of investigational medicine tralokinumab in atopic dermatitis
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EMBARGOED UNTIL: 29.10.20
- Phase 2b dose-finding study showed that delgocitinib cream demonstrated a statistically significant dose-response relationship compared with vehicle in adults with mild-to-severe chronic hand eczema, the most common skin disorder of the hands[i]
- Data for tralokinumab demonstrates positive safety profile, significant aureus colonisation reduction5 and no effect on vaccine response rates in adults with moderate-to-severe atopic dermatitis versus placebo[ii]
- Atopic dermatitis affects approximately 10% of the population[iii] while hand eczema can affect 5%,[iv] both negatively impacting quality of life
BERKSHIRE, UK, October 29, 2020 – Today, global leader in medical dermatology LEO Pharma A/S announced positive results of a Phase 2b dose-finding study with delgocitinib cream, an investigational topical pan-Janus kinase (JAK)-inhibitor, during the Late Breaking News session of the European Academy of Dermatology and Venereology (EADV) Virtual 2020 Virtual Congress.1 The results show that delgocitinib cream demonstrated a statistically significant dose-response relationship for both primary and secondary endpoints. The primary endpoint was the proportion of adult patients with mild-to-severe chronic hand eczema (CHE) who achieved an Investigator’s Global Assessment (IGA)-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline to Week 16.1 The secondary endpoint was change in Hand Eczema Severity Index (HECSI) from baseline to Week 16 compared with vehicle.1
Also presented was data from a pooled analysis of three pivotal Phase 2b and Phase 3 trials for tralokinumab, an investigational therapy for atopic dermatitis. The data show that the overall frequency of adverse events (AEs) with tralokinumab was comparable to placebo in the initial 16-week period when used as both a monotherapy and combination therapy with topical corticosteroid (TCS) mometasone furoate in adult patients with moderate-to-severe atopic dermatitis.2 Further, an exploratory analysis of the Phase 3 ECZTRA 1 trial showed that treatment with tralokinumab was associated with significant reduction in S. aureus colonisation compared with placebo at Week 16.[v] The Phase 2 ECZTRA 5 trial showed that the use of tralokinumab did not affect vaccine response rates of combined tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal vaccines.[vi]
Positive results of Phase 2b dose-finding study with delgocitinib cream
Delgocitinib inhibits activation of the JAK-STAT pathway, which plays a key role in the immune system in driving the pathophysiology of chronic inflammatory skin diseases.[vii],[viii] The cream formulation of delgocitinib is an investigational therapy under clinical development and has not been approved by any regulatory authority.
‘There is considerable unmet need for treatments to help individuals with chronic hand eczema, known as CHE, to manage their condition long term. CHE causes significant burden on people’s lives; impacting self-esteem and ability to do work,’ said Amit Aggarwal, Medical Director, LEO Pharma, Cluster North Europe, AU & NZ. ‘It is positive to see that the results of this trial suggest that delgocitinib cream could become a future treatment option for patients suffering from mild-to-severe CHE.’
Across all treatment groups, the majority of AEs were non-serious, mild or moderate in severity and not considered treatment related.1 In addition, none of the three serious AEs were considered treatment related,1 and the most frequently reported AEs were nasopharyngitis, eczema and headache.1
ECZTRA data reinforces safety profile of tralokinumab: Overall frequency of AEs compared with placebo, reduction in S. aureus colonisation and no effect on vaccine response rates of Tdap and meningococcal vaccines
Tralokinumab is an investigational, fully human monoclonal antibody that specifically neutralises the interleukin-13 cytokine—a key driver of the underlying chronic inflammation in atopic dermatitis in adults.[ix] It is an investigational therapy under clinical development, and its efficacy and safety are currently being evaluated by regulatory authorities, it has not yet been approved by any regulatory authority.
‘Atopic dermatitis is a chronic condition, negatively affecting people throughout their lives,’ says Dr Sandeep Cliff, Consultant Dermatologist and Clinical Lead in Dermatology, East Surrey Hospital. ‘Bacterial skin infections such as staphylococcal are common in atopic dermatitis. People with the condition also seem to have a reduced ability to fight the bacteria to prevent these common infections. This can create a vicious cycle, as the infection causes the condition to worsen and become more resistant to usual treatments. The results of this study are encouraging—providing healthcare professionals with potential new treatment options to help manage skin infections and improve patient quality of life.’
‘This promising data adds to the favourable benefit:risk profile of tralokinumab,’ said Amit Aggarwal, Medical Director, LEO Pharma, Cluster North Europe, AU & NZ. ‘Atopic dermatitis is a complex condition that has a far-reaching impact. Complications such as skin infections are common and can become difficult to manage, often requiring antibiotics. Therefore, this exploratory analysis showing a significant reduction in S. aureus colonisation in the tralokinumab arm compared with placebo is encouraging. It is also encouraging that, as a biologic therapy, no effects on vaccine response rates were reported with tralokinumab when compared with placebo. These data are an important advancement in the future treatment of this condition. At LEO Pharma, we are committed to developing effective treatments with favourable safety profiles—supporting healthcare professionals to assist with the treatment needs of their patients.’
Pooled Safety Data and Conjunctivitis
Overall frequency of adverse events (AEs) in the initial 16-week period was similar for tralokinumab (66%) compared with placebo (67%), and were recovered or resolved in 60% and 62% respectively.2 The majority were mild or moderate, and serious AEs occurred at a lower frequency for tralokinumab (2.1%) than placebo (2.8%).2 The proportion of AEs leading to permanent discontinuation up to 16 weeks of treatment was low and similar for tralokinumab and placebo (2.3% vs 2.8%).2
Data from the pooled analysis showed conjunctivitis occurred with higher frequency in patients treated with tralokinumab
(n = 1,605) vs placebo (n = 680) at a rate of 7.5% vs 3.2%.[x] Overall, 145 and 23 conjunctivitis events occurred in the tralokinumab and placebo groups, respectively.10
Staphylococcus Aureus (S. aureus) Colonisation and Vaccine Study
Results from an exploratory analysis of a Phase 3 trial (ECZTRA 1) (n = 802) showed tralokinumab 300 mg every 2 weeks (Q2W) (n = 603) was associated with a statistically significant reduction in Staphylococcus aureus (S. aureus) colonisation in lesional skin compared with placebo (n = 199) in adult patients with moderate-to-severe atopic dermatitis.5 Median S. aureus abundance was reduced more from baseline to Week 16 in patients receiving tralokinumab (n = 555) vs placebo (n = 184), with a 10-fold greater reduction for tralokinumab versus placebo-treated patients.5 A Phase 2 trial (ECZTRA 5) assessing vaccine responses in adults (n = 215) with moderate-to-severe atopic dermatitis who received combined tetanus, diphtheria, and acellular pertussis and meningococcal vaccines found that tralokinumab 300 mg delivered Q2W did not have an impact on vaccine response.6
ECZTRA pivotal Phase 3 trial data published in the British Journal of Dermatology—showing improvements in Severity and Quality of Life Measures in Adults with Atopic Dermatitis
In addition to the announcements at the European Association of Dermatology and Virtual 2020 Congress, LEO Pharma 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. Results demonstrated that treatment with tralokinumab with or without concomitant use of topical corticosteroids may provide sustained improvements in atopic dermatitis severity up to 52 weeks, and showed improvements in itch, sleep interference and quality of life measures versus placebo, which are important to clinicians and patients.[xi],[xii]
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.
Earlier this year, delgocitinib cream received Fast Track designation for the treatment of moderate-to-severe CHE from the U.S. Food and Drug Administration. The Fast Track process facilitates the development and expedites regulatory review of drugs to treat serious conditions and that demonstrate the potential to address an unmet medical need.[xiii]
About Chronic Hand Eczema
CHE is defined as hand eczema (HE) that lasts for more than 3 months or relapses twice or more within a year.[xiv],[xv] HE is a common skin disorder of the hands that affects an estimated 5% of the general population4 with a 1-year prevalence rate of approximately 0.4%.[xvi] It is an inflammatory, non-infectious skin disorder of the hands and wrists14,[xvii] and can cause itching, blisters, swelling and pain so severe that it can impair the ability to work.[xviii],[xix] In a substantial number of patients, HE can develop into a chronic condition.18
About ECZTRA 5 and Phase 2b Trials
ECZTRA 5 (ECZema TRAlokinumab trial No. 5) was a randomized, double-blind, placebo-controlled, 30-week, Phase 2 trial which included 215 adult patients, with atopic dermatitis to evaluate the effect of tralokinumab (300 mg) on vaccine antibody responses (Tdap and meningococcal vaccines) in adults with moderate-to-severe atopic dermatitis who are candidates for systematic therapy. Patients were treated with either tralokinumab or placebo for 16 weeks.[xx] The efficacy, safety and tolerability of tralokinumab when administered with the studied vaccines was also assessed.[xxi]
About atopic dermatitis
Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.[xxii] Type 2 cytokines, including interleukin-13, play a central role in the key aspects of atopic dermatitis pathophysiology.[xxiii] Atopic dermatitis is a chronic, inflammatory, heterogeneous skin disease characterised by intense itch and eczematous lesions.24
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
Virgo Health UK
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- Worm M, et al. The topical pan-JAK inhibitor delgocitinib cream demonstrates dose response in a 16-week phase 2b trial in chronic hand eczema. Presented during the Late Breaking News session of the European Academy of Dermatology and Venereology (EADV) Virtual 2020; 29–31 October 2020.
- Simpson E, et al. Safety of specifically targeting interleukin-13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomised, double-blind, placebo-controlled Phase 3 and Phase 2 trials. E-poster at European Academy of Dermatology and Venereology (EADV) Virtual Congress; 29–31 October 2020. P0218; Abstract 1464.
- Langan SM, et al. Atopic Dermatitis. Lancet 2020;396(10247):345–360.
- British Association of Dermatology. Hand Dermatitis / Hand Eczema [online] August 2019. Available from: https://www.bad.org.uk/shared/get-file.ashx?id=166&itemtype=document [Last accessed: October 2020].
- Bieber T, et al. Impact of targeting interleukin-13 on Staphylococcus aureus colonisation: results from a Phase 3, randomised, double-blind, placebo-controlled trial with tralokinumab in adult patients with atopic dermatitis. Oral presentation at EADV Virtual Congress; 29–31 October 2020. Abstract 1363.
- Merola J, et al. Vaccine antibody responses in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: results from the 30-week Phase 2 ECZTRA 5 trial. E-poster at European Academy of Dermatology and Venereology (EADV) Virtual Congress; October 29-31, 2020. P0181; Abstract 806.
- Damsky W and King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol 2017;76(4):736–744.
- Virtanen TA, et al. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs 2019;33(1):15–32.
- 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(2):208–219.
- Wollenberg A, et al. Conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: pooled results from five clinical trials. E-poster at EADV Virtual Congress; 29–31 October 2020. P0216; Abstract 1448.
- Silverberg 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. Br J Dermatol doi:10.1111/bjd.19573.
- Wollenberg, 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). Br J Dermatol doi: doi:10.1111/bjd.19574.
- S. Food and Drug Administration. Fast Track. Available from: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track [Last accessed: October 2020].
- Lynde C, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg 2010;14(6):267–284.
- Diepgen TL, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges 2015;13(1):e1–22.
- Crane MM, et al. Hand eczema and steroid-refractory chronic hand eczema in general practice: prevalence and initial treatment. Br J Dermatol 2017;176(4):955–964.
- Menné T, et al. Hand eczema guidelines based on the Danish guidelines for the diagnosis and treatment of hand eczema. Contact Dermatitis 2011;65(1):3–12.
- Bissonnette R, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Aacad Dermatol Venereol 2010;24 Suppl 3:1–20.
- Politiek K, et al. Systematic review of cost‐of‐illness studies in hand eczema. Contact Dermatitis 2016;65(1):3–12.
- gov. Vaccine Responses in Tralokinumab-Treated Atopic Dermatitis - ECZTRA 5 (ECZema TRAlokinumab Trial No. 5) (ECZTRA 5). NCT03562377. Available from: https://clinicaltrials.gov/ct2/show/NCT03562377 [Last accessed: October 2020].
- gov. Phase 2 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults with Atopic Dermatitis (Phase 2b). NCT02347176. Available from: https://clinicaltrials.gov/ct2/show/NCT02347176 [Last accessed: October 2020].
- Boguniewicz M and Leung DYM. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242(1):233–246.
- Tsoi LC, et al. Atopic dermatitis is an IL-13 dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol 2019;139(7):1480–1489.
- Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy 2020;75(1):54–63.
UK MAT- 39795 | October 2020