Anzupgo to address the unmet needs in chronic hand eczema

Professor Sonja Molin, Division of Dermatology, Department of Medicine at Queen's University

“Effective in all CHE subtypes... Overcomes limitations of existing drugs”

“Significance demonstrated through a head-to-head trial with alitretinoin”

Professor Sonja Molin, Division of Dermatology, Department of Medicine at Queen

Since their emergence, JAK inhibitors have rapidly expanded their therapeutic footprint.

 

Initially introduced as the first oral option in rheumatoid arthritis, a field previously reliant solely on injections, JAK inhibitors have since taken a pivotal role across the spectrum of autoimmune diseases, including ankylosing spondylitis, psoriatic arthritis, atopic dermatitis, and Crohn’s disease.

 

In this context, JAK inhibitors are now breaking yet another barrier in disease management by shedding even the notion of being an ‘oral formulation’ and entering the market as topical ointment formulations, ushering in a new paradigm shift.

 

In September, the Ministry of Food and Drug Safety granted marketing authorization for Anzupgo (delgocitinib), a treatment for chronic hand eczema (CHE).

 

Specifically, Anzupgo is indicated for the topical treatment of“moderate-to-severe chronic hand eczema in adults who have an inadequate response to, or for whom treatment with topical corticosteroids is not advisable.” As a non-steroidal, topical, pan-JAK inhibitor, Anzupgo inhibits the activation of the JAK-STAT cellular signaling pathway, known to play a key role in the manifestation of hand eczema.

 

Until now, treatment options for chronic hand eczema have been limited, with strong topical corticosteroids commonly used as first-line therapy.

 

However, its long-term use carries risks of various side effects, including skin barrier damage, skin atrophy, and telangiectasia.

 

Dailypharm met with Dr.

 

Sonja Molin, Professor of Dermatology at Queen's University, to discuss the clinical value and therapeutic potential of Anzupgo, the first topical JAK inhibitor for CHE.

 

Anzupgo cream

-What is chronic hand eczema, and what is its prevalence? CHE is one of the most common skin conditions affecting the hands, and a large proportion of cases progress to chronic disease.

 

CHE is known to affect approximately 1 in 10 adults worldwide.

 

This disease causes significant functional, occupational, and psychological burdens, significantly reducing patients' quality of life.

 

Approximately 70% of patients with severe CHE experience difficulties performing daily activities, which directly impacts their employment and income.

 

As a result, early diagnosis and appropriate treatment are paramount to effectively reduce the disease burden for these patients.

 

Therefore, raising awareness about CHE and expanding active treatment approaches are urgently needed.

 

Many patients only visit general practitioners rather than dermatologists, meaning a significant number of cases are not fully reflected in official statistics.

 

Consequently, the true prevalence of hand eczema is likely much higher than current estimates.

 

-Chronic hand eczema is known to be morphologically diverse.

 

Which subtypes primarily occur? CHE is a heterogeneous disorder influenced by multiple factors and manifests in various forms.

 

According to the 2022 European guidelines, CHE is categorized into etiological subtypes and clinical subtypes.

 

In practice, overlapping subtypes are quite common, with irritant contact dermatitis and allergic contact dermatitis being common causes.

 

Clinical subtypes like bullous or hyperkeratotic hand eczema also require careful treatment.

 

-Does Anzupgo show efficacy across all CHE subtypes? Anzupgo is approved for moderate to severe chronic hand eczema in adults who do not respond to or are not suitable for topical steroid therapy.

 

Results from the Phase III clinical trial supporting its approval demonstrated that delgocitinib cream showed broad therapeutic responsiveness across all CHE subtypes.

 

Mechanistically, Anzupgo not only provides anti-inflammatory effects but also helps restore the damaged skin barrier, making it suitable for treating irritant, allergic, vesicular, and hyperkeratotic subtypes.

 

Clinically, patients with thick, severe hyperkeratotic lesions may exhibit slower treatment response.

 

However, CHE is a chronic condition requiring long-term management, so continued treatment should be considered with expectations for gradual improvement.

 

-What limitations exist with previous CHE treatments, and how does Anzupgo differ? As a dermatologist, I have long felt that existing treatment options for CHE are inadequate.

 

For example, topical corticosteroids are internationally recommended as first-line therapy, but repeated long-term use often leads to diminished efficacy and local adverse effects, which are clear limitations.

 

Alitretinoin is the only oral medication approved specifically for CHE and is effective for symptom control.

 

However, concerns regarding teratogenicity restrict its use in women of childbearing potential, and routine lab monitoring is required, limiting its broader use.

 

This unmet need means the disease burden associated with patients' symptoms remains a challenge that needs to be addressed.

 

Therefore, the arrival of Anzupgo, a topical therapy with a novel mechanism and clinically proven efficacy and safety, is extremely welcome.

 

- You have real-world experience prescribing Anzupgo.

 

How do clinical outcomes compare with trial data? Having participated in the DELTA study, the pivotal clinical trial for Anzupgo, I was therefore already familiar with its efficacy and safety profile.

 

As a dermatologist treating patients with CHE, my primary concern was whether the efficacy and safety profile demonstrated in clinical trials would translate identically to real-world patient outcomes.

 

In conclusion, Anzupgo met these expectations and, in some cases, demonstrated even superior efficacy in real-world practice.

 

Notably, it showed excellent responsiveness in the bullous subtype of CHE, where response to existing medications was often poor.

 

Furthermore, the results of the DELTA FORCE study, which directly compared Anzupgo with the oral agent alitretinoin, are also impressive.

 

It was surprising that delgocitinib cream demonstrated statistically significant clinical results compared to alitretinoin in the primary endpoint (change in HECSI score at Week 12 from baseline) and all other efficacy parameters.

 

-When should patients previously treated with topical steroids consider switching to Anzupgo? If the response to topical corticosteroids is inadequate or relapses are frequent, the physician should consider other treatment options as early as possible.

 

Since its approval in Germany last September, the use of Anzupgo has steadily increased.

 

Awareness of delgocitinib cream is gradually growing among both healthcare professionals and patients, and overall treatment satisfaction is high.