Delgocitinib cream continues to perform well in chronic hand eczema (CHE), with limited systemic exposure, according to two studies presented at the 2024 Maui Dermatology conference.
Leo Pharma’s Delgocitinib is an investigational topical pan–Janus kinase inhibitor that inhibits activation of the JAK-STAT pathway.
In one study, researchers reported significant improvements in both clinician-assessed (Investigator Global Assessment or IGA-CHE treatment success, Hand Eczema Severity Index (HECSI) and patient-reported (Dermatology life Quality Index or DLQI) efficacy outcomes compared to cream vehicle. What’s more, delgocitinib cream 20 mg/g was well-tolerated over 16 weeks, and no safety concerns were identified.
For the study, adults with moderate to severe CHE received twice-daily delgocitinib cream 20 mg/g (n=314) or cream vehicle (n=159) for 16 weeks followed by a 2-week safety follow-up period or were transferred to a 36-week extension trial.
The primary endpoint was IGA-CHE treatment success at Week 16 (defined as an IGA-CHE score of 0/1 [clear/almost clear, i.e., no/barely perceptible erythema and no other signs] with ≥2-step improvement from baseline. Key secondary endpoints included HECSI-75 and HECSI-90 at week 16 and ≥4-point improvement in DLQI from baseline at week 16.
The proportion of patients who achieved the primary endpoint of IGA-CHE treatment success at week 16 was statistically significantly greater in the delgocitinib cream 20 mg/g group (29.1%) compared to the cream vehicle group (6.9%), the study showed.
Additionally, significantly more delgocitinib cream-treated patients achieved IGA-CHE treatment success at weeks 4 and 8 compared with the cream vehicle group, the study found.
At week 16, significantly greater proportions of patients in the delgocitinib cream 20 mg/g group achieved key secondary endpoints (HECSI-75/90, ≥4-point DLQI improvement from baseline) compared to the cream vehicle group.
These results are consistent with those reported from the identically designed DELTA 1 trial.
In a related study, twice daily application of delgocitinib cream 20 mg/g resulted in minimal systemic exposure in patients with moderate to severe CHE over 16 weeks.
The study included DELTA 2 trial analyses examining systemic exposure of twice-daily delgocitinib cream 20 mg/g treatment in moderate to severe CHE. This trial included samples from 313 people on active treatment.Researchers also compared systemic exposure data to corresponding Phase 1 trial data following oral administration of delgocitinib and the IC50 of delgocitinib.
The highest topical systemic exposure level (geometric mean: 0.21 ng/ml at Week 1) was ≥80-fold below the whole blood IC50 value of delgocitinib (17.2 ng/ml). Moreover, the highest topical systemic exposure level (geometric mean: 0.21 ng/ml at Week 1) was ≥30-fold lower than the lowest oral dose of delgocitinib tested (1.5 mg; 7.2 ng/ml) with no overlap in plasma exposure between oral and topical administration, the researchers reported.
Study author Melinda J. Gooderham, MD, Medical Director at the SKiN Centre for Dermatology and the Principal Investigator for the SKiN Research Centre in Peterborough, Ontario, Canada, chatted with the Dermatology Digest about the new studies and the dramatic impact that CHE has on patients’ lives.
“CHE can really impact patients and their quality of life from the time they wake up in the morning until retiring to bed at night,” she says. “We use our hands for almost everything we do throughout the day from washing and dressing to preparing food, driving, and interacting with other people — so swelling, scaling, fissuring can lead to pain, itch and impact many daily activities of living and your ability to work.”
Unmet Need
Topical steroids have been the mainstay of treatment for CHE over the years. “These medications have limitations including such side effects such as skin atrophy; can be aesthetically unpleasing (greasy, stains clothing, affect grip) and have had some bad press on social media with issues such as topical steroid withdrawal so patients may not be adherent to proper therapy and suffer from poor outcomes,” she explains.
Oral medications like alitretinoin are not available in all areas and not approved for use in the U.S so access to medications can be limiting. “Older conventional systemic agents such as methotrexate also have limitations such as end-organ toxicity,” she says.
The bottom line? “There is a great unmet need for this common and debilitating condition,” she says.
Enter JAK inhibition.
“There is great excitement because JAK inhibition has been a proven therapy that is effective and safe for a condition such as CHE and we have new options available for patients. JAK inhibitors are available orally, but given some safety concerns or contraindications, not all patients are suitable,” Dr. Gooderham says.
Topical delivery of JAK inhibitors represents a new way to treat CHE patients, and delgocitinib has been studied specifically in CHE with good efficacy and safety, without the concerns of systemic absorption.
Delgocitinib “provides CHE treatment success in 25-35% of patients within the first 16 weeks, and in the same time frame, half of patients will achieve 75% improvement in the HECSI,” she says.
CHE patients also reported significant quality of life improvement in the Maui Derm studies. “From a safety perspective, none of the safety concerns we see with oral jak inhibitors was seen – and a study looking at the systemic absorption of delgocitinib showed it was minimal and not associated with any adverse effects. “laboratory parameter changes or safety concerns with twice daily application. “
