GSK-1070806 (Aletekitug): A Comprehensive Clinical Development Review

1. Executive Summary

This report provides a comprehensive analysis of the clinical development program for GSK-1070806, also known by the proposed International Nonproprietary Name (INN) Aletekitug, a humanized monoclonal antibody developed by GlaxoSmithKline (GSK).[1] GSK-1070806 targets and neutralizes the pro-inflammatory cytokine Interleukin-18 (IL-18), a member of the IL-1 family implicated in various immune-mediated conditions.[1] By inhibiting IL-18, the therapy aims to reduce downstream inflammatory cascades, notably the production of interferon-gamma (IFN-γ).[6]

The clinical development of GSK-1070806 has spanned multiple indications, including Atopic Dermatitis (AD), Crohn's Disease (CD), Delayed Graft Function (DGF) following renal transplantation, and Type 2 Diabetes Mellitus (T2DM).[2] Currently, the primary focus is on Phase 2 development for moderate-to-severe AD, administered via subcutaneous injection.[1] Early Phase 1b results in AD showed promising clinical improvements and significant benefits in patient-reported outcomes, including itch and quality of life, compared to placebo.[14] A Phase 2b dose-finding study (NCT05999799) and a subsequent long-term extension study (NCT06447506) are ongoing to further evaluate efficacy and safety in this indication.[15] Development in CD reached Phase 2, but recent reports conflict regarding its current status.[3]

Conversely, development was discontinued for DGF and T2DM due to lack of efficacy demonstrated in Phase 2a trials.[3] Despite evidence of target engagement in both studies, GSK-1070806 failed to meet primary endpoints related to preventing DGF or improving glycemic control.[5] These outcomes highlight the challenge of translating IL-18 inhibition into clinical benefit across diverse conditions.