Background

Janus kinase (JAK)-mediated cytokine signaling contributes to local and systemic inflammation in hidradenitis suppurativa (HS).

Objectives

To describe safety and efficacy results from two multicenter phase 2 trials of the JAK1 inhibitor INCB054707 in patients with moderate-to-severe HS.

Methods

Patients received open-label 15 mg INCB054707 once daily (QD; Study 1) or were randomized to 30, 60, or 90 mg INCB054707 QD or placebo (3:1 within each cohort; Study 2) for 8 weeks. Eligible patients were aged 18–75 years with moderate-to-severe HS (Hurley stage II/III disease), lesions present in ≥2 anatomic locations, and a total abscess and inflammatory nodule count ≥3. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures.

Results

Ten patients were enrolled in Study 1 (15 mg INCB054707) and 35 in Study 2 (INCB054707: 30 mg, n=9; 60 mg, n=9; 90 mg, n=8; placebo: n=9). Overall, 70·0% of patients in Study 1 and 80·8% of patients receiving INCB054707 in Study 2 experienced ≥1 treatment-emergent adverse event (TEAE); 30·0% and 42·3% of patients, respectively, had ≥1 treatment-related TEAE. Among evaluable patients, 3 patients (42∙9%) in Study 1 and 17 patients (overall 65·4%: 30 mg, 55·6%; 60 mg, 55·6%; 90 mg, 87·5%) receiving INCB054707 versus 4 patients (57·1%) receiving placebo in Study 2 achieved HiSCR at Week 8.

Conclusions

INCB054707 was well tolerated, with responses observed in patients with moderate-to-severe HS. Safety and efficacy findings from these studies demonstrate proof of concept for JAK1 inhibition in HS (ClinicalTrials.gov identifiers, NCT03569371, NCT03607487).