Week 1, September 2024: Prurigo Nodularis & FDA Approvals

In August, the US FDA approved Galderma’s Nemluvio (nemolizumab) for adult patients living with prurigo nodularis (PN). Nemluvio is the first approved monoclonal antibody specifically inhibiting the signaling of IL-31, a neuroimmune cytokine that drives multiple disease mechanisms in (PN). Prurigo nodularis is a chronic skin condition that affects approximately 181,000 patients in the United States, and is characterized by persistent, intense itch. Initially developed by Chugai Pharmaceutical Co., Ltd. in 2016, Galderma obtained exclusive rights to the development and marketing of nemolizumab worldwide, except in Japan and Taiwan. In Japan, nemolizumab is approved for the treatment of both PN and pruritus associated with atopic dermatitis in pediatric, adolescent, and adult patients.

Meanwhile, a recent paper by Yook & Lee describes the pathogenesis and horizon of other potential therapeutics, including antibodies that target Th2 polarization. Novel drugs such as tralokinumab have demonstrated encouraging outcomes. As an anti-IL-13 monoclonal antibody, it demonstrated a significant reduction in itch severity as early as week 4 in a case series of patients with a PN-like phenotype of AD. Targeting oncostatin M beta receptor (OSMRβ) may also help, as it is the shared receptor for IL-31 and OSM. Thus, the monoclonal antibody vixarelimab (KPL-716) disrupts IL-31 signaling and is currently under assessment in AD and PN. Other potential targets include IL-5 with benralizumab and KIT with barzolvolimab.

Another article by Liao et al. puts the current perspectives succinctly: Current understanding of prurigo nodularis (PN) links the condition to immune system imbalances that lead to widespread inflammation and nerve dysregulation in the skin. Elevated immune molecules, such as interleukins (IL)-4, -13, -17, -22, and -31, contribute to systemic inflammation in PN patients, while activated inflammatory cells like mast cells and eosinophils release factors that exacerbate inflammation, itch, and neural changes. PN's neural dysregulation is characterized by a lower density of itch-sensing nerve fibers in the epidermis and a higher density in the dermis. Due to the incomplete understanding of PN's pathogenesis, current therapies have had limited success in alleviating itch and nodules.