Difelikefalin is currently being studied as a new treatment for eczema (atopic dermatitis). Itching or pruritis is the most burdensome symptom of eczema. It has a negative impact on quality of life. Inflammation is driven primarily by TH2 cytokines (IL-4 and IL-13). There are also other mediators that play a role as well (IL-31, TSLP, CCL2.
Dysregulation of the opioid system may contribute to itching as well. In the periphery, K-Opioid receptors (KORs) are located in the skin. KOR agonists can inhibit itching. Oral Difelikefalin is a KOR agonist.
A phase 2 clinical trial investigated the safety of oral difelikefalin in subjects with moderate to severe atopic dermatitis related pruritis. All difelikefalin patients had reduced itch versus placebo, subjects had itch dominant atopic dermatitis (mild to moderate skin inflammation and moderate to severe itch). Treatment in subjects reduced the expression of biomarkers related to pruritis and inflammation, including the TH2 pathway.
Currently, topical agents are the only approved therapies with patients to mild to moderate eczema, but they are associated with poor adherence and low treatment satisfaction. There remains an unmet need for oral medications in eczema, as many patients use oral antihistamines in the management of their disease.
Difelikefalin may be a therapeutic option because it can target nonhistaminergic pruritis. Currently treatment for that is lacking. Intravenous difelikfalin was approved in 2021 for the treatment of moderate to severe itching in adults undergoing hemodialysis.
In a recent study titled “Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis”, it showed a potential neuromodulatory role for reducing itch in atopic dermatitis. The key points were that it reduced atopic dermatitis itch independent of skin inflammation. Difelikefalin acts as a neuromodulator to reduce itching.
Most new medications for eczema are either topical creams, or injectable medications. There is an unmet need for oral medications for eczema that could benefit patients who symptoms are mainly itching.