Abrocitinib is currently being developed by Pfizer for the treatment of atopic dermatitis (eczema). It is an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor.
The JAK/STAT pathway is an important factor in inflammation and itch in atopic dermatitis. There are multiple receptors and signaling cascades involved in eczema related inflammation and itch, one of these is the JAK/STAT pathway.
Cytokine signaling is responsible for sustaining the inflammatory response in both the acute and chronic phases of eczema. The following cytokines are part of the JAK/STAT pathway and by inhibiting them, improved eczema may be seen if the studies work.
- IL-4, IL-13, IL-31, TSLP and IL-22 are key cytokines responsible for maintaining inflammation and itch in atopic dermatitis.
- IL-31 and TSLP are key itch cytokines in atopic dermatitis, while IL-4 and IL-13 also contribute to pruritis.
- IL-4, IL-13, and IL-31 can bind to receptors on sensory neurons in the skin leading to chronic pruritis through a non-histamine-dependent pathway.
In previous blog posts we have discussed the importance of some of these cytokine signaling pathways used for eczema.
Cytokine binding and subsequent signaling occurs via the JAK/STAT pathway.
- The JAK family has 4 members: JAK1, JAK2, JAK3, and TYK2
- After a cytokine binds to its receptor on the surface of a target cell, cytokine receptors dimerize, bringing JAK pairs into close proximity.
- The JAKs then phosphorylate members of the STAT family, which translocate to the nucleus and affect gene transcription to perpetuate inflammation and itch.
The burden and impact of atopic dermatitis is immense. It is estimated to 7.2% of adults and 10.7% of children in the U.S have it. 46% of patients report limited disease control or uncontrolled atopic dermatitis. Up to 87% of adults wake up at night due to itching. Up to 60% of children experience sleep disruptions caused by their disease. Lack of sleep can cause poor performance in school. There is a large psychological impact with sleep disorders, anxiety and depression related to atopic dermatitis.
There are a lot of different treatments available for atopic dermatitis, Abrocitinib would be for the more severe eczema who have failed conventional therapy.
Recently Pfizer announced positive data from one of its trials. Positive top-line results from the Phase 3 JADE TEEN study of abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, in patients 12 to <18 years of age with moderate to severe atopic dermatitis (AD) who were also on background topical therapy. Both doses of abrocitinib met the co-primary endpoints and were generally well tolerated.
Other trials as well have showed good results. Phase 3 results show abrocitinib safe, effective for atopic dermatitis
Abrocitinib currently doesn’t have a brand name or a price yet. Further studies will need to be done on Abrocitinib before its approved. The most common adverse effects seen are upper respiratory tract infection, headache, nausea, and diarrhea.
The Lancet recently published a phase 3 randomized placebo controlled trial (JADEMONO-1) to assess the efficacy of abrocitinib. Improvements in pruritis and disease burden were observed at week 2 of treatment and continued throughout the rest of the 12 week study. Notably it was well tolerated. This supports abrocitinb as a potential treatment for atopic dermatitis, although further studies with longer duration of treatment are required.
Stay tuned for more information on studies of Abrocitinib.