Plasma biomarkers for clinical response and disease severity identified from Hidradenitis Suppurativa patients in the phase II AURORA study

Background: Hidradenitis Suppurativa (HS) is a chronic debilitating skin disease that is graded into Hurley stages I, II, and III based on severity. In the double-blind Phase II AURORA study (NCT03852472), patients with moderate (II) or severe (III) HS were randomized to receive placebo, 10 mg, or 30 mg twice daily avacopan, an orally administered selective C5a receptor inhibitor. Patients with severe disease who received 30 mg avacopan had a significantly higher Hidradenitis Suppurativa Clinical Response (HiSCR) rate at 12 weeks compared to the placebo group. Plasma samples were collected from 68 patients enrolled in the study at baseline and 12 weeks post treatment, and from an independent age and gender matched healthy cohort. The levels of 31 biomarkers including plasma complement factors, chemokines, and cytokines were assessed in order to identify biomarkers for patients that demonstrated a clinical response to 30 mg avacopan and to differentiate patients with severe from moderate disease. The resulting data were analyzed using logistic regression modeling of natural log transformed biomarker values. We identified a subset of 6 factors that predicted response to 30 mg avacopan. In addition, a separate modeling showed clear differences between moderate and severe disease samples, with contributions from complement, matrix metalloproteinases, and neutrophil factors. Our results support severe HS as a distinct disease state compared to moderate HS, and provide candidate predictive biomarkers for clinical benefit from avacopan treatment.