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

  • 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 hands1
  • Data for tralokinumab demonstrates positive safety profile, significant S. aureus colonisation reduction5 and no effect on vaccine response rates in adults with moderate-to-severe atopic dermatitis versus placebo2
  • Atopic dermatitis affects approximately 10% of the population3 while hand eczema can affect 5%,4 both negatively impacting quality of life

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 16.5 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.6

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.7,8 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.9 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.

‘These are very interesting data highlighting positive advancements towards two potential new therapies to help healthcare professionals better support the treatment needs of their eczema patients,” said Prof. Alan Irvine, Professor of Dermatology, Trinity College Dublin. “Atopic dermatitis and chronic hand eczema are both chronic conditions, that can significantly affect people’s long-term health and wellbeing, physically and psychologically. With atopic dermatitis, the immune system is highly sensitive and can react to even the smallest allergens or irritants, so this data could be an important milestone in the development of treatment options which can be well tolerated among these patients, with minimal adverse reactions.’

 ‘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%.9 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.11,12

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.

 

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