Late-Breaking Data: Povorcitinib Significantly Improves Itch and Lesions in Prurigo Nodularis

New late-breaking data on phase 2 safety and efficacy data of oral povorcitinib for prurigo nodularis was presented at the 2024 American Academy of Dermatology (AAD)Annual Meeting in San Diego, California.¹

In the phase 2 study of oral povorcitinib (NCT05061693), a small molecule JAK1-selective inhibitor, 126 adult patients with ≥20 pruriginous lesions, an Investigator’s Global Assessment (IGA) score of ≥3, prurigo nodularis for ≥3 months, and an average itch Numerical Rating Scale (NRS) score of ≥5 were randomized to receive once-daily povorcitinib (15, 45, or 75 mg) or placebo for 16 weeks.

The primary end point of the phase 2 study was a ≥4-point improvement in itch NRS score (NRS4) at week 16, which was achieved by significantly more patients who received povorcitinib(15mg: 36.1% [P=0.0066],45mg: 44.4% [P=0.0006], 75mg: 54.1% [P<0.0001]) vs placebo (8.1%).

Median times to NRS4 were 58.0 days for 15mg, 35.0 days for 45mg, and 17.0 days for 75mg povorcitinib vs not estimable for placebo. IGA Treatment Success (IGA score of 0 or 1 with a ≥2-grade improvement from baseline) at week 16 was achieved by 13.9%, 30.6%, and 48.6% of patients receiving povorcitinib (15, 45, and 75 mg, respectively) vs 5.4% for placebo.

The most common adverse events (AEs) among povorcitinib-treated patients were headache (11.1%) and fatigue (9.3%). Discontinuations due to AEs were infrequent (povorcitinib, n=5 [4.6%]; placebo, n=1 [2.7%]). Grade ≥3 AEs and serious AEs occurred in 4 (3.7%) and 9 (8.3%) povorcitinib-treated patients, respectively.

The study authors concluded that “povorcitinib demonstrated a clinical impact on itch and prurigo nodularis lesions, was generally well tolerated, and represents a promising novel approach to treat this debilitating condition.”

First author Shawn Kwatra, MD, associate professor of dermatology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Itch Center, in Baltimore, Maryland, spoke to Dermatology Times at AAD 2024 about the significance of this phase 2 study and its results.

"I'm very thankful and have a lot of gratitude that I had the opportunity to have my hands all over the design of this trial. It was actually based on a lot of our laboratory's data, where we performed the first immunophenotyping studies from the skin and blood of prurigo nodularis patients. And in these patients, we looked at the different compartments and found high IL-22, from CD4+ CD8+ T-cells, high IL-4 and IL-13 in subsets, IL-31, and also IL-6," said Kwatra.

Transcript

Shawn Kwatra, MD: Hi, I'm Shawn Kwatra from Baltimore, Maryland. The phase 2 data of povorcitinib in prurigo nodularis is incredibly exciting for our field and prurigo nodularis. I'm very thankful and have a lot of gratitude that I had the opportunity to have my hands all over the design of this trial. It was actually based on a lot of our laboratory's data, where we performed the first immunophenotyping studies from skin and blood of prurigo nodularis patients. And in these patients, we looked at the different compartments and found high IL-22 from CD4+ CD8+ T-cells, high IL-4 and IL-13 in subsets, IL-31, and also IL-6. So, we actually had the idea about doing JAK inhibitors in prurigo nodularis, we did the dose-ranging trial with povorcitinib, and you can see that it was remarkably effective at itch and also nodule reduction at that 16-week marker and the 75mg dose in particular had very robust and rapid reduction in itch with an acceptable safety profile as well in the study. So it's incredibly exciting that we had a very potent agent, and had positive results as well, and hopefully the program should be moving forward and we're looking forward to the pipeline expanding in prurigo nodularis.

[Transcript lightly edited for space and clarity.]

Reference

Martin M. Efficacy and safety of oral povorcitinib in patients with prurigo nodularis: results from a randomized, double-blind, placebo-controlled phase 2 study. Presented at: 2024 American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA.