Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study

Abstract

Background: Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms.

Objective: To assess efficacy and safety of povorcitinib (selective oral Janus kinase 1 inhibitor) in HS.

Methods: This placebo-controlled phase 2 study randomized patients with HS 1:1:1:1 to receive povorcitinib 15, 45, or 75 mg or placebo for 16 weeks. Primary and key secondary end points were mean change from baseline in abscess and inflammatory nodule count and percentage of patients achieving HS Clinical Response at week 16.

Results: Of 209 patients randomized (15 mg, n = 52; 45 mg, n = 52; 75 mg, n = 53; placebo, n = 52), 83.3% completed the 16-week treatment. At week 16, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, -5.2 [0.9], P = .0277; 45 mg, -6.9 [0.9], P = .0006; 75 mg, -6.3 [0.9], P = .0021) versus placebo (-2.5 [0.9]). More povorcitinib-treated patients achieved HS Clinical Response at week 16 (15 mg, 48.1%, P = .0445; 45 mg, 44.2%, P = .0998; 75 mg, 45.3%, P = .0829) versus placebo (28.8%). A total of 60.0% and 65.4% of povorcitinib- and placebo-treated patients had adverse events.

Limitations: Baseline lesion counts were mildly imbalanced between groups.

Conclusion: Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses.

Keywords: DLQI; FACIT-F; HS; HiSCR; HiSQoL; IHS4; INCB054707; JAK1; JAK1 inhibitor; clinical trial; efficacy; hidradenitis suppurativa; itch; oral administration; patient-reported outcomes; placebo-controlled; povorcitinib; skin pain.