The U.S. Food and Drug Administration (FDA) has approved delgocitinib cream (Anzupgo, LEO Pharma) for the topical treatment of moderate-to-severe chronic hand eczema (CHE) in adults who have had an inadequate response to, or for whom topical corticosteroids are not advisable.
“In my career as a dermatologist, I have witnessed firsthand the significant burden that the itch and pain of CHE places on patients, and the challenges they face living with it,” says Linda Stein Gold, MD, Director of Clinical Research in the Department of Dermatology at Henry Ford Health in Detroit, MI, in a news release. “I believe this new treatment option will be welcomed by dermatologists who are looking for effective and safe ways to address these symptoms.”
Delgocitinib cream inhibits the janus kinase/signal transducer and activator of the transcription (JAK-STAT) pathway, specifically blocking the activity of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), and suppresses the various inflammatory responses that play a key role in the onset and subsequent flares of CHE.
Based on Two Studies
The FDA approval of delgocitinib cream is based on two pivotal randomized, double-blind, vehicle-controlled studies of identical design, DELTA 1 and DELTA 2, that evaluated the safety and efficacy of delgocitinib cream in a total of 960 patients, aged 18 and older with moderate-to-severe CHE. The primary efficacy endpoint of both trials was the Investigator’s Global Assessment for chronic hand eczema treatment success (IGA-CHE TS) at Week 16, defined as a score of 0 (clear) or 1 (almost clear) with at least a two-point improvement from baseline.
In DELTA 1, 20% of patients treated with delgocitinib cream achieved this outcome versus 10% with the cream vehicle (p = 0.006). In DELTA 2, 29% of delgocitinib-treated patients achieved IGA-CHE TS compared to 7% for the cream vehicle. Both trials also met all their key secondary endpoints. Using the Hand Eczema Symptom Diary (HESD) to measure the severity of itch (n=949) and pain (n=875) in CHE patients, at Week 16, 49% of patients treated with delgocitinib cream in DELTA 1 and 49% in DELTA 2 achieved a ≥four-point reduction in the HESD pain score, compared to 28% and 23% for pain in the cream vehicle groups.
Further, at Week 16, 47% of patients treated with delgocitinib cream in DELTA 1 and 47% in DELTA 2 achieved a ≥four-point reduction in the HESD itch score, compared to 23% and 20% for itch in the cream vehicle groups.
Clinical studies found that delgocitinib cream offers a favorable safety profile comparable to the cream vehicle. Adverse reactions that were reported in ≤1% of subjects were application-site pain, paresthesia, pruritus, erythema, bacterial skin infections, other skin infections, leukopenia, and neutropenia.
Experts React to “Game-changing” Approval
“CHE is so difficult to treat because it is usually multifactorial in etiology, creating a situation in which Th1, Th2, and Th17 cytokines can all be relevant,” Matthew Zirwas, MD, Founder of the Bexley Dermatology Research Clinic in Bexley, OH, tells TDD. “Thus, a broad spectrum inhibitor is necessary, especially one that targets TYK2, which is the main enzyme in the JAK family that is part of the Th17 pathway. While topical steroids are broad-spectrum anti-inflammatories, they degrade barrier function and formation with only a few days of use. So having a topical JAK that is broad-spectrum and doesn’t negatively impact the barrier should be a game-changer for our CHE patients.”
Raj Chovatiya, MD, PhD, Founder and Director of the Center for Medical Dermatology and Immunology Research in Chicago, IL, agrees. “The approval of delgocitinib cream is a major step forward for us both therapeutically and clinically in dermatology,” he says. “On the therapeutic front, delgocitinib is a first-in-class topical pan-JAK inhibitor that addresses the underlying inflammatory pathogenesis of CHE. On the clinical front, delgocitinib’s approval is validation of CHE as a common, burdensome, and underserved disease state that is in dire need of safe, effective, and highly targeted topical treatments. I look forward to finally having a rigorously studied, approved treatment option for my CHE patients.”
“We’re thrilled that the FDA recognizes the impact that moderate-to-severe chronic hand eczema has on patients,” says Kristin Belleson, CEO and President of the National Eczema Association. “People living with a debilitating skin disease on their hands find it extremely difficult; it can impact their ability to work, touch, and connect with important people in their lives. The approval of ANZUPGO provides hope and promise for the eczema community and those seeking lasting relief from disruptive symptoms.”
LEO Pharma is working to make delgocitinib cream available to patients in the U.S. as soon as possible and is committed to supporting broad, affordable access to all its treatments. More information is available at ANZUPGO.com.
