Journal of the European Academy of Dermatology and Venereology : JEADV · 2026
Safety and pharmacokinetics of anumigilimab for hidradenitis suppurativa or palmoplantar pustulosis: A phase 1b study.
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Kern Johannes S, Thomsen Simon Francis, Kokolakis Georgios, Podda Maurizio, Jemec Gregor B E, Gebauer Kurt, Zachariae Claus, Frew John, Fernandez-Peñas Pablo, Bechara Falk G, Beissert Stefan, Malandkar Sourabh, Scalzo-Inguanti Karen, Nandy Partha, Sukumar Selvakumar
Аннотация
BACKGROUND: 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)].
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.