Early clinical trial results are suggesting a novel drug designed to inhibit the activity of a key immune signaling molecule could become a promising new treatment for atopic dermatitis, a very common inflammatory skin condition. These positive Phase 2a trial results have accelerated the research into larger, placebo-controlled clinical trials.
IL-33 is an immune signaling protein released by a number of different cell types in the body in response to conditions such as infection or stress. The molecule acts a little like an immune system alarm, summoning other immune system cells to a damaged site.
Excessive IL-33 production has been linked to a number of autoimmune conditions such as asthma, allergies and eczema. For over a decade, scientists have been working on developing a drug that can effectively inhibit the activity of IL-33. Called etokimab, the novel drug is now displaying promising early human trial results, suggesting it could be a groundbreaking new therapeutic agent to treat several autoimmune disorders linked to excessive IL-33 activity.
“We’ve been studying the role of IL-33 in human skin for nearly 10 years, with the lab work suggesting IL-33 might be a potential target for therapies,” explains Graham Ogg, lead on the new clinical trial. “So we are pleased that in this first human trial in patients with atopic dermatitis, we have confirmed that the IL-33 pathway appears to be a therapeutic target in its own right.”
This early Phase 2a trial involved 12 patients with moderate to severe atopic dermatitis. Impressively, all twelve patients displayed at least a 50 percent improvement in symptomatic severity four weeks after a single intravenous dose of etokimab. Follow-up observations around two months after the single dose revealed sustained responses, with the vast majority of subjects still displaying symptomatic improvements.
The researchers also closely examined the cohort’s skin inflammatory responses, both before and after the etokimab treatment. A few days after the drug was administered each subject was administered a skin allergen challenge to investigate whether the body’s immune response was subdued by the new drug. The treatment did notably reduce the volume of immune cells, called neutrophils, reaching the challenged skin site. This suggests the etokimab treatment does suppress inflammatory immune activity, and implies the specific anti-IL-33 treatment may be helpful for a number of autoimmune conditions related to excessive neutrophils activity.
“This exciting experimental medicine trial is an excellent example of how long-term support for fundamental science leads to new treatments for diseases that severely affect the quality of life for millions of people,” says Patrick Chinnery, clinical director at the Medical Research Council in the UK. “As this is the first study of its kind, the trial also suggests that IL-33 may have an important role in a number of immune-mediated disorders which will also lead to new avenues of research for other conditions.”
Etokimab is also currently being trialled to treat eosinophilic asthma. Phase 2a clinical trial data testing the drug on that disorder were reported earlier in the year and demonstrated similar promising results. A larger Phase 2b human trial is about to get underway verifying efficacy for that condition.
Ogg does note it is still early days for the prospective new therapy. These promising results affirm the drug’s safety profile and demonstrate initial efficacy, but there is a long road ahead to verify these results in large cohorts before the new treatment is clinically available.
“These results are only very preliminary, and we need to be cautious,” Ogg adds. “But we’re currently testing the therapy in a larger double-blind randomized trial in people with atopic dermatitis and we look forward to seeing the results. New antibody therapies, like etokimab, are exquisitely specific in what they target and they have the potential to help patients and to help us better understand disease.”
The new results were published in the journal Science Translational Medicine.