Analysis of Predefined Safety Events Across Spesolimab Trials in Dermatological and Non-Dermatological Conditions

Abstract Introduction Spesolimab, a selective, humanised monoclonal antibody targeting the interleukin-36 receptor, is approved for the treatment of generalised pustular psoriasis (GPP). As a result of the limited patient numbers in GPP trials of spesolimab, analysing safety events across dermatological and non-dermatological diseases helps to further characterise the known safety profile of spesolimab. Here, we analyse predefined safety events from nine randomised, placebo-controlled spesolimab trials across dermatological (including GPP) and gastrointestinal conditions. Methods Predefined safety events were based on the known safety profile of spesolimab across all diseases investigated to date and potential risks of biological therapeutics, and included serious/severe/opportunistic infections, hypersensitivity, malignancies and peripheral neuropathy. Results Including placebo-controlled trials and open-label periods/trials, 589 patients received ≥ 1 dose of spesolimab (772.2 patient-years; mean exposure 1.31 patient-years). Overall, 452 patients had long-term exposure (≥ 6 months) to spesolimab, with 31 patients up to ≥ 3 years. In placebo-controlled periods, 445 patients had exposure to spesolimab (162.0 patient-years; mean exposure 0.36 patient-years). Severe/serious/opportunistic infections occurred in 0–3.2% of spesolimab-treated patients and 0–14.3% of placebo-treated patients. Malignancies occurred infrequently across trials (0–6.7% in spesolimab, 0–2.3% in placebo). Peripheral neuropathy events also occurred infrequently, with single events reported in the placebo arm of EFFISAYIL® 2, and the spesolimab and placebo arms of palmoplantar pustulosis Study 2. Potential hypersensitivity events occurred in all trials, except for Crohn’s disease, and were largely balanced between spesolimab (7.7–33.3%) and placebo (4.3–44.4%). Conclusions Across placebo-controlled periods of spesolimab trials in dermatological and non-dermatological conditions, severe/serious/opportunistic infections, malignancies and peripheral neuropathy events were low, with no evidence for an increased risk with spesolimab versus placebo. Potential hypersensitivity events were similar between spesolimab and placebo. These results support the favourable safety profile of spesolimab observed in EFFISAYIL® 2, the largest GPP trial conducted to date. Graphical Abstract