Late-Breaking Data: 40-Week Efficacy and Safety of Oral Povorcitinib for Prurigo Nodularis

Shawn Kwatra, MD, presenting at EADV 2024

Image courtesy of Kwatra

A late-breaker presentation¹ at the 33rd European Academy of Dermatology and Venereology (EADV) Congress held September 25 through 28 in Amsterdam, Netherlands, detailed the 40-week results of a phase 2 study (NCT05061693) evaluating the safety and efficacy of oral povorcitinib (Incyte), a JAK1 inhibitor, for the treatment of prurigo nodularis. Previously, povorcitinib demonstrated early itch improvement, a meaningful impact on IGA scores, and was well-tolerated in a 16-week phase 2 dose-ranging study. The 40-week study was designed to assess the longer-term safety and efficacy of response-based povorcitinib dosing in patients from the phase 2 dose-ranging study.

“Our lab has done research showing that several JAK1 cytokines are upregulated in patients with prurigo nodularis. We discovered IL-22 in the blood increased and IL-13 increased. We also found that IL-6 is a JAK1 cytokine upregulating in prurigo nodularis as compared to atopic dermatitis. So, there’s a lot of rationale for why to use povorcitinib in prurigo nodularis,” said Shawn Kwatra, MD, professor and chair of the department of dermatology at the University of Maryland School of Medicine, in a statement to Dermatology Times.

Kwatra presented the late-breaking data as a first author, global principal investigator of the oral povorcitinib clinical trials, and an itch expert.

The 40-week long-term study included adult patients aged 18 to 75 years with prurigo nodularis in a 16-week double-blind placebo-controlled treatment period, followed by a 24-week single-blind extension period. Inclusion criteria included a diagnosis of prurigo nodularis for ≥3 months, ≥20 pruriginous lesions on ≥2 body regions, an IGA score ≥3, an itch NRS score ≥5, and an inadequate response or intolerance to previous treatment. Patients were randomized 1:1:1:1 to receive povorcitinib 15mg every day (QD; n=36), povorcitinib 45mg QD (n=36), povorcitinib 75mg QD (n=37), and placebo QD (n=37) during the 16 weeks.

The primary end point was the proportion of patients achieving a ≥4-point improvement from baseline in Itch NRS (NRS4) at week 16. Key secondary end points included the proportion of patients achieving IGA treatment success (IGA-TS; an IGA score of 0 or 1 with a ≥2-grade improvement from baseline at week 16 and time to Itch NRS4.

Patients who received povorcitinib45mg QD and achieved both Itch NRS4 and IGA-TS, or a composite response, without needing rescue therapy during the placebo-controlled period were considered responders. Patients who received povorcitinib 75mg QD and did not achieve Itch NRS4 and IGA-TS were considered non-responders.

In total, most patients reported severe itch with their prurigo nodularis and the mean DLQI scores suggested the condition has a “very large effect” on their quality of life.

At week 16, significantly more patients receiving povorcitinib achieved Itch NRS4 than those receiving placebo. Patients who received 75mg of povorcitinib showed the fastest efficacy and achieved Itch NRS4 within a median of 19 days. For the 45mg and 15mgpovorcitinib groups, the median days to Itch NRS4 were 35 and 58 days, respectively. At week 16, the patients who received 75mg of povorcitinib demonstrated a greater proportion of those achieving IGA-TS compared with the lower povorcitinib doses or placebo, but to a “lesser extent than itch responses.” The majority of responders came from the 45mg and 75mg povorcitinib groups.

Other key results include:

• Among the week 16 responders, 89% of patients achieved individual Itch NRS4 and IGA-TS responses after treatment with 45mg of povorcitinib through week 40
• Among the week 16 responders, 63% of patients achieved Itch NRS4+IGA-TS composite response at week 40 after treatment with 45mg of povorcitinib through weeks 18 to 40
• Among the week 16 non-responders, povorcitinib 75mg led to increasing Itch NRS4 responses from 34% at week 16 to 70% by week 40
• 48% of non-responders who originally received placebo and who switched to povorcitinib 75mg achieved composite responses after 12 weeks of treatment in the extension period

“This study really paves the way for a phase 3 study, and it makes sense to use a JAK inhibitor in prurigo nodularis,” Kwatra told Dermatology Times.

Overall, there were minimal grade ≥3 treatment-emergent adverse events (AEs) or serious AEs, and povorcitinib was well tolerated with no new safety signals.

“Povorcitinib is a promising, novel, oral treatment for patients with prurigo nodularis, with the potential for early and long-term disease control. Future studies will investigate if longer treatment durations with povorcitinib 45mg or 75mg are beneficial for achieving Itch NRS4+IGA-TS composite responses," concluded Kwatra et al.

Reference

1. Kwatra S, Metz M, Yosipovitch G, et al. Efficacy and Safety of oral povorcitinib in patients with prurigo nodularis: 40-week results from a randomized, double-blind, placebo-controlled phase 2 study. Presented at: 33rd European Academy of Dermatology and Venereology Congress; September 25-28, 2024; Amsterdam, Netherlands.