San Diego — Data from an open-label extension study of delgocitinib cream reflects the positive phase 3 safety and efficacy results released> 1 year ago from two separate trials in patients with chronic hand eczema.
In a phase 3 extension study of patients with moderate to severe chronic hand eczema, presented as a late breaker at the annual meeting of the American Academy of Dermatology, the efficacy and the tolerability of as needed delgocitinib cream was maintained over 16 weeks of additional follow-up with no change in the earlier conclusions about its favorable safety and efficacy, according to Melissa Gooderham, MD, assistant professor at Queen’s University, Kingston, Canada, and medical director of the Skin Centre for Dermatology.
After 36 weeks of follow-up, like the earlier 16-week results, “the benefits are there for both efficacy and safety,” Gooderham said.
The pivotal DELTA 1 and DELTA 2 trials have not yet been published, but results were released at the end of 2022 and beginning of 2023, respectively. The full details of the DELTA 1 study were presented at the 2023 AAD meeting, and details of DELTA 2 were presented as a poster at the 2023 meeting of the European Academy of Dermatology and Venereology.
Phase 3 Delgocitinib Studies Were Positive
Both of the identically designed studies showed the topical pan-Janus kinase (JAK) inhibitor to be effective for the primary endpoint of an Investigator’s Global Assessment of chronic hand eczema (IGA-CHE) defined as a score of 0 or 1 (clear or almost clear). In pooled data from the two multinational trials, which together randomized 960 patients in a 2:1 ratio to a twice-daily application of 20 mg/g delgocitinib or its vehicle, the rates of clear or almost clear were 24.3% and 8.4% (P <.001 respectively.>
In the extension DELTA 3 trial, 560 patients initially treated with delgocitinib and 241 patients initially randomized to placebo were enrolled for an additional 16 weeks of therapy. Improvement in the IGE-CHE score among those who had been on vehicle was seen quickly after they were rolled over to the JAK inhibitor in the extension trial. By week 36, clear or almost clear responses were almost identical among those who started on delgocitinib or were rolled over (30.0% and 29.5%, respectively).
The safety of delgocitinib, the primary focus of DELTA 3, showed the same type of favorable safety and tolerability seen in the earlier studies. In those trials, serious adverse events were uncommon, occurring in ≤ 7% of patients in any arm, and none were considered to be treatment-related, Gooderham reported.
“In DELTA 3, most patients reported no or mild tolerability issues, and the proportion was slightly higher at week 36 compared to week 1 [90.2% vs 83.9%],” she said.
Looking at specific adverse events in DELTA 3, all occurred at rates no higher than 5%-7%, except for nasopharyngitis and COVID-19, which occurred in 25%-30% of enrolled patients, respectively. For those who were on continuous delgocitinib, back pain appeared to be slightly less common than in those initiated on placebo and switched to the JAK inhibitor (3.44% vs 5.08%).
Secondary and Primary Endpoints Were Consistent
The secondary efficacy endpoints were consistent with the IGA-CHE. On the Hand Eczema Severity Index (HECSI), about half of those randomized to delgocitinib in DELTA 1 and DELTA 2 achieved a score of 75 (HECSI-75), signaling a 75% reduction in lesions and symptoms, such as pruritus and pain. At the end of DELTA 3, this proportion remained unchanged, according to Gooderham.
For the higher bar of HECSI-90, just under a third of patients met this level of success at the end of the 16-week phase 3 studies, and the proportion had not changed at the end of the extension. The proportion of patients with a Dermatology Life Quality Index improvement of ≥ 4 points from baseline, which is considered clinically significant, was also maintained over the extended follow-up.
Given the limitations of prolonged topical steroid use, which is one of the most common therapies prescribed for chronic eczema, Gooderham indicated that this JAK inhibitor could address an important unmet need if and when it is approved. Delgocitinib cream has already been approved in Japan.
Currently, “there are no topical treatments specifically developed and approved for chronic hand eczema,” Gooderham said. She noted that there is no evidence that topical application of delgocitinib as recommended results in systemic exposure.
Need for Hand Eczema Therapy Is Strong
The need for an effective therapy for eczema of the hands is substantial, according to Raj Chovatiya, MD, PhD, assistant professor of dermatology, at Northwestern University, Chicago, Illinois, who was asked to comment on the results. Chovatiya has written frequently about atopic dermatitis in general, including a patient information article last year in the Journal of the American Medical Association, and about the role of JAK inhibitor therapy for this disease specifically.
“Chronic hand eczema is the bane of our existence in dermatology given its multifactorial etiology and lack of targeted therapies that can address the multiple pathologies of the disease,” Chovatiya told Medscape Medical News.
“The DELTA 3 study shows that the as-needed twice daily use of delgocitinib cream over the 36-week extension period, modeling the real-world topical-use patterns of our patients, led to consistent treatment success alongside a favorable safety profile,” he added.
He echoed the remarks of Gooderham, specifying that DELTA 3 results “strongly support delgocitinib as a potential topical first-in-class, pan-Janus kinase inhibitor for the treatment of chronic hand eczema.”
Gooderham spoke on March 9, 2024, in the late-breaking abstract session of the AAD meeting in San Diego, California.
Gooderham reported financial relationships with more than 35 pharmaceutical companies, including Leo Pharma, which sponsored the DELTA phase 3 studies of delgocitinib. Chovatiya reported financial relationships with about 15 pharmaceutical companies, including those that produce JAK inhibitors, but he has no financial relationship with Leo Pharma.
Ted Bosworth is a medical journalist based in New York City.
>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Medscape – https://www.medscape.com/viewarticle/chronic-hand-eczema-longer-term-data-reported-topical-2024a100071k
