Safety and pharmacokinetics of anumigilimab for hidradenitis suppurativa or palmoplantar pustulosis: A phase 1b study.
Source: PubMed, NCBI / U.S. National Library of Medicine
We report the first study of anumigilimab, a novel anti-G-CSFR antibody, in patients with neutrophil-driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)]. This phase 1b, open-label, repeat-dose study (NCT03972280) comprised 15-week treatment and 9-week follow-up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21-day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment-emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response. Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab-related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment-related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal-finding exploratory analyses, 57.9% of patients with HS (n = 11/19 with data
Abstract
We report the first study of anumigilimab, a novel anti-G-CSFR antibody, in patients with neutrophil-driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)]. This phase 1b, open-label, repeat-dose study (NCT03972280) comprised 15-week treatment and 9-week follow-up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21-day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment-emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response. Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab-related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment-related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal-finding exploratory analyses, 57.9% of patients with HS (n = 11/19 with data at Week 15) achieved ≥50% HS Clinical Response, IHS4 score decreased by 40.3%, and patients with PPP experienced a 40.4% reduction in ppPASI score. These clinical responses were not dose dependent, possibly due to imbalanced baseline characteristics and small sample size. Anumigilimab was generally well tolerated in patients with HS or PPP, with no serious treatment-related safety concerns, and demonstrated dose-dependent pharmacology. While clinical responses in HS and PPP were observed, it should be noted that these observations were exploratory and signal-finding in nature. Importantly, the study was not powered to statistically confirm efficacy and lacked a placebo control, underscoring the need for future randomized, placebo-controlled trials to validate these preliminary signal-finding observations.