Work

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

Year: 2025

Type: article

Abstract: 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. 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. 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%). 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. Spesolimab is a drug used to treat generalised pustular psoriasis (GPP), a life-long skin disease. It is also being studied for the treatment of other conditions. As GPP is a rare disease, doctors can better understand the safety profile of spesolimab by looking at any health problems (adverse events, AEs) that happen during clinical studies of spesolimab across other diseases. By doing this, it is possible to learn more about the chance of developing certain AEs when spesolimab is used for GPP. This analysis looked at the risk of specific AEs of spesolimab across nine clinical trials, in participants who were randomly allocated to receive either spesolimab or a placebo (non-active medicine). AEs were studied on the basis of information about spesolimab from all diseases investigated so far. These included serious/severe/opportunistic infections, damage to nerves not located in the brain or spinal cord (peripheral neuropathies), cancerous tumours and allergic or abnormal reactions of the body’s defence system (hypersensitivity reactions). Few participants experienced serious/severe/opportunistic infections, peripheral neuropathies and cancerous tumours. These AEs were not more common in participants who received spesolimab compared with placebo. Some participants across the studies had hypersensitivity reactions, except for those with Crohn’s disease (a disease that causes inflammation in the digestive tract). This AE was equally as common in participants who received spesolimab and placebo. No deaths occurred in any trial. These data show that the safety profile of spesolimab is favourable. This aligns with results from the EFFISAYIL® 2 study, the largest study in GPP to date.

Source: Dermatology and Therapy

DOI: 10.1007/s13555-024-01325-7