A Comprehensive Monograph on Secukinumab (DB09029)

Executive Summary and Overview

Introduction

Secukinumab, marketed globally under the brand name Cosentyx®, represents a significant milestone in the management of immune-mediated inflammatory diseases (IMIDs). It is a first-in-class, fully human immunoglobulin G1 kappa (IgG1/κ) monoclonal antibody that selectively targets and neutralizes the proinflammatory cytokine Interleukin-17A (IL-17A).[1] Developed by Novartis, Secukinumab's introduction has fundamentally altered the therapeutic landscape for a spectrum of debilitating chronic conditions, offering a highly targeted mechanism of action that distinguishes it from broader immunosuppressive agents.[1] Its development and approval have validated the IL-17 pathway as a critical therapeutic target in autoimmunity.

Core Mechanism and Therapeutic Rationale

The therapeutic rationale for Secukinumab is rooted in its precise inhibition of IL-17A, a pivotal cytokine produced primarily by T helper 17 (Th17) cells.[1] In numerous IMIDs, the IL-23/IL-17 axis is dysregulated, leading to an overproduction of IL-17A, which drives a cascade of inflammatory responses.[4] By binding with high affinity and specificity to IL-17A, Secukinumab prevents the cytokine from interacting with its receptor on various cell types, including keratinocytes and synoviocytes.[1] This action effectively interrupts the downstream signaling that promotes inflammation, tissue damage, and the clinical manifestations of diseases such as psoriasis and spondyloarthropathies.[4] This targeted approach represents a significant evolution from less specific therapies, aiming to maximize efficacy while minimizing off-target effects.

Synopsis of Indications and Efficacy