Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: results from the phase II GALLOP trial

Background Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that can be severe, debilitating and life threatening. Uncontrolled activation of interleukin (IL)-36 proinflammatory activity may underlie the pathogenesis of GPP. Currently, GPP-specific treatment options are limited. Objectives To evaluate the efficacy and safety of the anti-IL-36 receptor antibody imsidolimab in patients with GPP. Methods In an open-label, single-arm, multiple-dose study, patients with GPP were treated with imsidolimab to assess clinical efficacy, tolerability and safety. Patients received an intravenous dose of imsidolimab 750 mg on day 1, followed by three subcutaneous doses of imsidolimab 100 mg administered on days 29, 57 and 85. The primary efficacy endpoint was the proportion of patients who achieved a clinical response at weeks 4 and 16 following treatment with imsidolimab, as measured by the Clinical Global Impression scale. Results Eight patients were enrolled and six completed the study. Responses were observed as early as day 3, most rapidly for pustulation relative to other manifestations of GPP, with continued and consistent improvement across multiple efficacy assessments at day 8, day 29 and through day 113. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. No patient discontinued the study owing to a nonserious TEAE. Two patients experienced serious adverse events (SAEs); no deaths were reported. Conclusions Imsidolimab demonstrated a rapid and sustained resolution of symptoms and pustular eruptions in patients with GPP. It was generally well tolerated, with an acceptable safety profile, and is advancing to phase III trials. These data support the targeting of IL-36 signalling with a specific antibody - imsidolimab - as a therapeutic option for this severely debilitating condition. In this phase II trial of imsidolimab, an anti-interleukin-36 receptor antibody, patients with generalized pustular psoriasis (GPP) demonstrated a rapid and sustained improvement in symptoms and pustular eruptions of GPP flare after imsidolimab treatment. Six of eight patients achieved the primary endpoint at weeks 4 and 16. Imsidolimab was generally well tolerated, with an acceptable safety profile, and is advancing to phase III trials.