Investigational Drug Meets Endpoint in Study of Patients with Rare Skin Disorder

Povorcitinib, an oral JAK1 inhibitor, met the end points in a phase 2 study treating patients with prurigo nodularis, a chronic, inflammatory skin disease that causes hard and itchy nodules to form on the skin. The disease affects about 87,000 adults per year, according to the National Organization for Rare Diseases database. Prurigo nodularis has been linked to inflammatory cytokines and chemokines that signal through the JAK/STAT pathway.

The data were presented at the American Academy of Dermatology (AAD) Annual Meeting, recently held in San Diego.

The study met the endpoints following 16 weeks of treatment across all dosing groups, including the primary endpoint of a four-point improvement in the itch Numerical Rating Scale (NRS4) score. The dosages studied include 15 mg, 45 mg or 75 mg given once a day. The study enrolled 146 adults who were intolerant or had an inadequate response to a previous therapy for 16 weeks, followed by an extension of 24 weeks with the either the 45 mg or 75 mg dose. Developed by Incyte, povorcitinib is a small molecule inhibitor of JAK1.

“PN is a condition that can cause itchy bumps on the skin called nodules, which appear after excessive scratching. Despite the severity of the disease and the significant impact it can have on a patient’s day-to-day life, there remains a significant need for effective treatments,” Kurt Brown, M.D., vice president and povorcitinib global program head, Incyte, said in a press release.

Povorcitinib was generally well-tolerated. The most common treatment-emergent adverse events (TEAEs) among patients who received povorcitinib were headache, fatigue, and nasopharyngitis. Grade ≥3 TEAEs and serious TEAEs occurred in four and nine povorcitinib-treated patients, respectively, and discontinuations due to adverse events were infrequent.

Incyte officials said a phase 3 trial of povorcitinib is being planned to treat patients with prurigo nodularis. Phase 2 studies of povorcitinib in patients with prurigo nodularis, asthma and chronic spontaneous urticaria are ongoing.

Additionally, Incyte in October 2023 announced 52-week data from a phase 2b clinical trial evaluating the safety and efficacy of povorcitinib in adult patients with extensive nonsegmental vitiligo. In this trial, patients taking povorcitinib saw improvement in both mean percentage total body depigmentation and mean percentage facial depigmentation, the primary endpoints. Vitiligo is a chronic autoimmune disease characterized by depigmentation of skin that results from the loss of pigment-producing cells known as melanocytes. Overactivity of the JAK signaling pathway is believed to drive inflammation involved in the pathogenesis and progression of vitiligo.