Topical delgocitinib holds whip hand over oral systemic Tx in head-to-head hand eczema trial

In the phase III head-to-head DELTA FORCE trial, topical delgocitinib cream gains the upper hand over oral alitretinoin – the only oral systemic therapy approved for the treatment of severe chronic hand eczema (CHE) in adults with inadequate response to topical corticosteroids.

“Topical delgocitinib cream 20 mg/g demonstrated superior clinical treatment effects and quality-of-life (QoL) improvements, and a more favourable safety profile compared with oral alitretinoin over 24 weeks across the primary and all secondary endpoints in patients with severe CHE,” said Dr Ana Maria Giménez-Arnau from the Universitat Pompeu Fabra, Barcelona, Spain, at EADV 2024.

The primary endpoint was met, with delgocitinib cream rendering a significantly greater least squares mean (LSM) drop in HECSI* score from baseline to week 12 compared with alitretinoin (–67.6 vs –51.5; p<0.001). [EADV 2024, abstract 7986]

Delgocitinib also bested alitretinoin across key secondary endpoints, as reflected by the greater fraction of participants achieving HECSI-90* (38.6 percent vs 26 percent; p=0.003) and IGA-CHE TS** (27.2 percent vs 16.6 percent; p=0.004) and the greater LSM drops in HESD*** itch (–3 vs –2.4; p=0.005) and pain (–2.9 vs –2.3; p=0.018) at week 12.

The topical cream also trumped the oral alternative in terms of the LSM area under the curve for HECSI-90 (49.2 vs 34.9) and for change in DLQI^# (1,124.7 vs 790.7), as well as change in HECSI score (–69.6 vs –45.1; p<0.001 for all) at week 24.

Giménez-Arnau noted that the improvements with delgocitinib were consistent throughout the treatment period and manifested as early as week 1.

There were fewer treatment-emergent adverse events (AE) with the topical vs the oral treatment option (49.4 percent vs 76.1 percent), as well as serious AEs (2 percent vs 4.9 percent) and AEs leading to permanent drug discontinuation (1.2 percent vs 10.1 percent).

No approved topical treatment yet

CHE is a fluctuating disorder characterized by itch, pain, and bothersome signs such as erythema, scaling, hyperkeratosis, vesicles, oedema, and fissures on the hands and wrists. [Contact Dermatitis 2022;86:357-378] As a result, these manifestations lead to psychological and functional burdens that negatively impact patients’ QoL. [Adv Ther 2020;37:692-706; Contact Dermatitis 2014;70:158-168; Acta Derm Venereol 2022;102:adv00626]

“Current treatments for CHE are often unsatisfactory, and there are no topical treatments specifically developed and approved for CHE,” Giménez-Arnau said.

Delgocitinib cream – an investigational topical pan-Janus kinase inhibitor – has shown significant improvement in all key efficacy endpoints and was well tolerated in the phase III DELTA 1, 2, and 3 trials, she noted.

In DELTA FORCE, 513 participants (median age 45 years, 65 percent women) with severe CHE were randomized 1:1 to topical delgocitinib cream 20 mg/g BID for 16 weeks or oral alitretinoin 30 mg QD for 12 weeks (as per label; could be reduced to 10 mg). Participants may continue treatment until week 24 should they relapse or do not achieve sufficient benefit with their respective regimens during the initially proposed treatment time.

The median duration of CHE was 4 years. The median HECSI and DLQI scores were 80 and 12, respectively, while the median HESD itch/pain scores were 6.2/6.

“Our data support the benefits of delgocitinib cream 20 mg/g as an efficacious and well-tolerated topical treatment in this patient population with a high disease burden and unmet treatment needs,” said Giménez-Arnau.

A new topical option?

“The completion of the DELTA FORCE study marks a significant milestone in our understanding of moderate-to-severe CHE treatment,” said LEO Pharma Chief Development Officer Kreesten Meldgaard Madsen, in a news release. “With the full results now available, we have gained a new understanding of how topical treatment with delgocitinib cream compares with alitretinoin.”

“[These] data not only enhance our knowledge of CHE management but also potentially pave the way for a new topical option in clinicians’ therapeutic arsenal,” added LEO Pharma Head of Global Medical Affairs Alexander Egeberg.