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

Secukinumab has demonstrated robust, rapid, and sustained efficacy across a progressively expanding list of indications approved by major regulatory bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). These indications include moderate-to-severe plaque psoriasis (PsO), active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), active non-radiographic axial spondyloarthritis (nr-axSpA), moderate-to-severe hidradenitis suppurativa (HS), and several pediatric conditions, including enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA).[1] An extensive body of clinical trial evidence consistently shows high rates of clinical response, as measured by standard indices such as the Psoriasis Area and Severity Index (PASI 75/90/100), American College of Rheumatology criteria (ACR20/50), and Assessment of SpondyloArthritis international Society criteria (ASAS20/40).[3] In head-to-head trials and long-term studies, its performance has been shown to be superior to placebo and competitive with, or superior to, other established biologics.[3]

Safety and Market Position

The safety profile of Secukinumab is well-characterized through extensive clinical trials and over a decade of real-world use, with more than 5.2 million prescriptions filled in the United States alone.[16] The most common adverse events are mild to moderate upper respiratory tract infections.[2] As a consequence of its mechanism of action, there is an increased risk of certain infections, particularly mucocutaneous candidiasis.[13] Important warnings include the potential for new onset or exacerbation of inflammatory bowel disease (IBD) and the need for pre-treatment screening for tuberculosis.[18] A key differentiator is that Secukinumab does not carry an FDA black box warning, in contrast to some other biologics targeting the IL-17 pathway.[13] This favorable risk-benefit profile, combined with its proven efficacy and convenient dosing, has established Secukinumab as a leading therapeutic choice and a cornerstone treatment for its approved indications.[16]

Molecular Profile, Manufacturing, and Mechanism of Action

Biochemical and Physicochemical Identity

Secukinumab is a highly specific, engineered biologic therapeutic classified as a recombinant, fully human monoclonal antibody.[1] Its structure conforms to the immunoglobulin G1 kappa (IgG1/κ) isotype, a common framework for therapeutic antibodies known for its long half-life and effector functions.[23] The molecule is a large, symmetrical protein with a molecular weight of approximately 148 to 151 kDa.[4] It is composed of four polypeptide chains: two identical heavy chains, each comprising 457 amino acids, and two identical light chains, each with 215 amino acids.[25] These chains are covalently linked by inter-chain disulfide bonds, forming the characteristic 'Y' shape of an antibody.[27] A critical feature of its structure is the presence of N-linked oligosaccharide chains attached to the heavy chains, a post-translational modification essential for proper protein folding, stability, and function.[26]

Secukinumab is known by the developmental code AIN457 and is identified by the Chemical Abstracts Service (CAS) Number 1229022-83-6 and DrugBank Accession Number DB09029.[1] For clinical use, it is formulated as a sterile, preservative-free liquid solution that is clear to slightly opalescent and colorless to slightly yellow.[20] It is supplied in various single-use formats, including pre-filled syringes, auto-injector pens (Sensoready® and UnoReady®), and a lyophilized powder for reconstitution, which is intended for use by healthcare professionals.[2] In 2023, an intravenous formulation was also approved, expanding its administration options.[2] The formulation is precisely controlled for physicochemical properties such as pH and osmolality to ensure stability and patient tolerability upon injection.[24]

Parameter	Description	Source(s)
Generic Name	Secukinumab	1
Brand Name	Cosentyx®	2
DrugBank ID	DB09029	1
CAS Number	1229022-83-6	24
Type	Biotech, Monoclonal Antibody	1
Source	Fully Human	1
Target	Interleukin-17A (IL-17A)	1
Isotype	IgG1/κ	1
Molecular Weight	Approx. 151 kDa	23
Manufacturer	Novartis	2
Table 1: Drug Identification and Physicochemical Properties

Biopharmaceutical Manufacturing Process

The production of Secukinumab is a complex, multi-stage biopharmaceutical process that underscores the sophistication of modern biotechnology. Unlike small-molecule drugs synthesized through chemical reactions, biologics like Secukinumab are produced by living cells, making the manufacturing process itself a critical determinant of the final product's quality, safety, and efficacy. The process is broadly divided into upstream processing, where the antibody is produced by cells, and downstream processing, where it is purified and formulated.[33] This complexity creates a high barrier to entry for manufacturing and is a primary driver of the cost of biologic therapies, while also explaining the slower development of biosimilars compared to generic small-molecule drugs.

Upstream Processing

The foundation of Secukinumab manufacturing lies in upstream processing, which begins with cell line development and culminates in the large-scale production of the antibody.[33]

1. Cell Line Development: Secukinumab is produced in a Chinese Hamster Ovary (CHO) cell line.[2] CHO cells are the industry standard for producing complex therapeutic proteins because they are robust and capable of performing essential post-translational modifications, such as human-like glycosylation patterns, which are crucial for the antibody's stability, function, and minimizing its potential to be recognized as foreign by the patient's immune system.[27] The process starts with recombinant DNA technology, where the genetic sequences encoding the human heavy and light chains of Secukinumab are cloned into expression vectors. These vectors are then introduced into CHO cells through transfection.[27] A rigorous selection process follows to identify and isolate the cell clones that produce the highest quantities of the antibody with the correct structural attributes.[35]
2. Cell Culture and Expansion: The selected high-producing CHO cell line is cultivated in large, sterile, stainless-steel or single-use bioreactors, with volumes that can scale up to 5,000 liters or more for commercial production.[33] The cells are grown in a precisely controlled environment where parameters like temperature, pH, dissolved oxygen, and nutrient levels are continuously monitored and adjusted to optimize cell growth and antibody secretion.[38] The culture medium is chemically defined, serum-free, and often protein-free, which maximizes productivity and greatly simplifies the subsequent purification steps by reducing the amount of contaminating proteins.[34]

Downstream Processing

Once the bioreactor culture has reached its peak antibody concentration, the downstream processing phase begins. This phase is designed to harvest, purify, and formulate the antibody to the exceptionally high standards required for a human therapeutic.[33]

1. Harvest and Clarification: The first step is to separate the Secukinumab-containing culture medium (supernatant) from the CHO cells and other cellular debris. This is typically accomplished through a combination of centrifugation and depth filtration, resulting in a clarified harvest that is ready for purification.[38]
2. Purification Cascade: The clarified supernatant undergoes a multi-step purification process designed to isolate Secukinumab from remaining impurities, such as host cell proteins (HCPs), host cell DNA, and antibody variants or aggregates. The goal is to achieve a purity level exceeding 99%.[24] A typical purification train includes:

• Capture Chromatography: The primary capture step almost universally employs Protein A affinity chromatography. The Protein A ligand, immobilized on a resin, has a high affinity for the Fc region of IgG antibodies, allowing Secukinumab to bind tightly while most impurities flow through. The bound antibody is then eluted by changing the pH.[39]
• Viral Inactivation and Clearance: To ensure viral safety, one or more dedicated viral clearance steps are incorporated. This often includes a low-pH hold to inactivate enveloped viruses, followed by nanofiltration to physically remove any remaining viral particles based on size.[39]
• Polishing Steps: Following the capture step, one or more "polishing" chromatography steps are used to remove any residual impurities. These commonly include ion exchange chromatography (IEX) to separate proteins based on charge differences and hydrophobic interaction chromatography (HIC) to remove aggregates and other closely related impurities.[39]

3. Formulation and Fill-Finish: After the final purification step, the highly pure antibody solution is concentrated via ultrafiltration/diafiltration and exchanged into its final formulation buffer. This buffer contains specific excipients (e.g., buffering agents, stabilizers) designed to maintain the antibody's stability and prevent degradation during storage.[33] The final, formulated drug product is then aseptically filtered and filled into its final sterile containers (vials, syringes, or pens) in a process known as fill-finish.[38]

Quality Control

Throughout the entire manufacturing process, rigorous quality control testing is performed. A battery of analytical tests is used to monitor the product at every stage, ensuring its identity, purity, potency, and safety. Key quality attributes that are closely monitored include protein concentration, levels of aggregates and fragments, post-translational modifications like glycosylation, endotoxin levels (which must be extremely low, typically <1 EU/mg), and biological activity, which is confirmed using a cell-based assay that measures the antibody's ability to neutralize IL-17A.[24]

The "fully human" designation of Secukinumab is a critical design element with profound clinical implications. It is generated using transgenic mouse technology, where mice are engineered to express the human immunoglobulin gene repertoire instead of their own.[40] When these mice are immunized, they produce fully human antibodies. This approach bypasses the need for "humanization" of a mouse antibody, a process that can still leave some murine sequences that might be recognized as foreign by the human immune system. The direct consequence of this fully human origin is a very low potential for immunogenicity—the formation of anti-drug antibodies (ADAs). Clinical data robustly support this, showing an ADA rate of only 0.4% in large Phase III trials, with no associated loss of efficacy or safety signals.[43] This low immunogenicity is a significant clinical advantage, reducing the risk of treatment failure and hypersensitivity reactions that can plague other biologic therapies and contributing to the drug's long-term viability and reliability for patients.

The IL-17 Pathway and Pathophysiology

To understand the mechanism of Secukinumab, it is essential to first appreciate the central role of the Interleukin-17 pathway in the pathogenesis of the diseases it treats. The IL-17 family consists of six related cytokines (IL-17A through IL-17F), but IL-17A is the signature and most potent cytokine of this family, playing a master role in orchestrating chronic inflammation.[1]

IL-17A is produced predominantly by a specialized subset of CD4+ T cells known as T helper 17 (Th17) cells.[1] In healthy individuals, these cells are crucial for host defense, particularly at mucosal surfaces and in clearing fungal and extracellular bacterial infections. However, in a range of IMIDs, this pathway becomes dysregulated. Genetic predisposition and environmental triggers can lead to the over-activation of the IL-23/IL-17 axis.[4] The cytokine IL-23 promotes the expansion and maintenance of pathogenic Th17 cells, which in turn leads to the excessive production and release of IL-17A into tissues and circulation.[7]

Once released, IL-17A exerts its powerful proinflammatory effects by binding to its receptor, the IL-17 receptor (IL-17R), which is widely expressed on numerous cell types, including epithelial cells (like keratinocytes in the skin), endothelial cells, and stromal cells (like fibroblasts and synoviocytes in the joints).[1] The binding of IL-17A to its receptor initiates a cascade of intracellular signaling events, primarily through the activation of key transcription factors such as Nuclear Factor kappa B (NF-κB) and pathways like the mitogen-activated protein kinases (MAPKs).[5]

This signaling cascade results in the transcription and release of a host of other proinflammatory molecules, including:

• Cytokines: Such as Tumor Necrosis Factor-alpha (TNF-α), IL-1, and IL-6, which amplify the inflammatory response.[4]
• Chemokines: Such as CXCL1 and CXCL8, which are potent chemoattractants for neutrophils, recruiting them in large numbers to the site of inflammation.[6]
• Mediators of Tissue Damage: Including matrix metalloproteinases (MMPs) that can degrade cartilage and bone.

In the context of specific diseases, this leads to distinct pathologies. In plaque psoriasis, the action of IL-17A on keratinocytes drives their hyperproliferation, leading to the characteristic thickened, red, and scaly plaques (acanthosis and parakeratosis).[1] In

psoriatic arthritis and ankylosing spondylitis, IL-17A promotes synovial inflammation (synovitis), inflammation at the site of tendon and ligament insertions (enthesitis), and drives the processes of bone erosion and pathological new bone formation that lead to joint damage and fusion.[2]

Mechanism of Action of Secukinumab

Secukinumab exerts its therapeutic effect through a highly targeted and specific mechanism: the direct neutralization of IL-17A.[1]

As a high-affinity monoclonal antibody, Secukinumab is designed to selectively bind to circulating IL-17A with high precision.[3] This binding action physically prevents IL-17A from docking with its receptor (IL-17R) on target cells.[1] By blocking this crucial first step in the signaling pathway, Secukinumab effectively silences the entire downstream inflammatory cascade that IL-17A would otherwise trigger.[9]

A key feature of Secukinumab's design is its remarkable specificity. It potently neutralizes IL-17A but does not significantly bind to or inhibit other members of the IL-17 family, such as IL-17F.[4] While IL-17F is also proinflammatory, IL-17A is considered the dominant pathogenic driver in these diseases.[6] This deliberate therapeutic strategy of targeting only IL-17A is based on the hypothesis that this focused approach can achieve maximal clinical efficacy while potentially preserving some of the distinct physiological functions of other IL-17 cytokines, which could contribute to a more favorable long-term safety profile compared to broader-acting agents that block the common IL-17 receptor.

The pharmacodynamic effects of this mechanism are profound and measurable. In patients with plaque psoriasis, treatment with Secukinumab leads to a rapid reduction in the clinical signs of the disease—erythema (redness), induration (thickness), and desquamation (scaling)—and a normalization of the skin's histology.[1] In patients with psoriatic arthritis and ankylosing spondylitis, it leads to a marked decrease in systemic inflammatory markers like C-reactive protein (CRP) and tangible improvements in joint swelling, tenderness, and enthesitis.[2] By attenuating the release of proinflammatory cytokines and chemokines, Secukinumab effectively dampens the chronic inflammatory state, providing symptomatic relief and potentially modifying the long-term course of the disease.[1] An interesting pharmacodynamic observation is that total serum IL-17A levels (which include both free IL-17A and the drug-bound complex) increase during treatment. This reflects the formation of stable secukinumab-IL-17A complexes, which have a longer half-life than free IL-17A before they are eventually cleared from the body.[1]

Clinical Pharmacology: Pharmacokinetics and Drug Interactions

Pharmacokinetics (ADME Profile)

The pharmacokinetic (PK) profile of Secukinumab is characteristic of a human IgG1 monoclonal antibody, defined by slow absorption after subcutaneous injection, limited distribution, slow clearance, and a long elimination half-life. This profile is consistent across its approved indications and provides the scientific basis for its convenient dosing schedules.[4]

Absorption

Following subcutaneous (SC) administration, Secukinumab is absorbed slowly into the systemic circulation. Peak serum concentrations (Cmax​) are typically reached approximately 5 to 6 days post-injection.[1] For a 300 mg dose in plaque psoriasis patients, the mean

Cmax​ is 27.3 ± 9.5 mcg/mL.[1] The absolute bioavailability of SC-administered Secukinumab is high, estimated to be in the range of 55% to 77%, indicating efficient uptake from the subcutaneous tissue.[1] With the standard maintenance regimen of dosing every 4 weeks, steady-state serum concentrations are achieved by week 24, ensuring consistent therapeutic exposure over the long term.[1] The drug exhibits linear pharmacokinetics, meaning that exposure increases proportionally with the dose, and there is no evidence of dose-dependent clearance.[44]

Distribution

Secukinumab exhibits a small volume of distribution, indicating that it primarily remains within the vascular and interstitial spaces rather than distributing widely into tissues. The mean volume of distribution during the terminal phase (Vz​) has been measured to be between 7.10 and 8.60 L in patients with plaque psoriasis receiving the drug intravenously.[1] This limited distribution is typical for large protein molecules like monoclonal antibodies. Despite this, clinically relevant concentrations are achieved in target tissues. Studies have shown that in psoriatic skin, concentrations of Secukinumab in the interstitial fluid can reach 27% to 40% of the levels found in the serum, allowing it to effectively neutralize IL-17A at the site of inflammation.[6] Body weight has been identified as a significant covariate affecting the drug's PK, with both clearance and volume of distribution increasing in patients with higher body weight.[6]

Metabolism

As a large protein therapeutic, Secukinumab is not metabolized by the hepatic cytochrome P450 (CYP) enzyme system, which is the primary pathway for the metabolism of small-molecule drugs.[4] Instead, it is presumed to be broken down through general protein catabolism pathways. The antibody is likely taken up by cells via endocytosis and degraded into smaller peptides and individual amino acids, which are then recycled by the body.[4] This metabolic route implies that its clearance is not significantly affected by hepatic or renal impairment, simplifying its use in patients with comorbidities affecting these organs.[4]

Excretion

The systemic clearance (CL) of Secukinumab is low, ranging from 0.14 to 0.22 L/day.[6] This slow clearance is a direct result of its IgG1 structure, which allows it to engage the neonatal Fc receptor (FcRn) pathway. This pathway effectively rescues the antibody from lysosomal degradation and recycles it back into circulation, greatly extending its lifespan in the body. Consequently, Secukinumab has a long mean elimination half-life, estimated to be between 22 and 31 days.[6] This favorable pharmacokinetic property is the cornerstone of the convenient once-monthly maintenance dosing regimen, which enhances patient adherence and quality of life—critical factors in the management of chronic diseases.

Drug Interaction Profile

The drug interaction profile of Secukinumab is favorable, with few clinically significant interactions identified, primarily due to its metabolic pathway as a large protein.

CYP450 Substrates

Secukinumab does not directly inhibit or induce cytochrome P450 enzymes. However, an indirect interaction is possible. The expression and function of certain CYP450 enzymes can be suppressed by elevated levels of proinflammatory cytokines (e.g., IL-1, IL-6, TNF-α) that are characteristic of chronic inflammatory states.[1] By effectively treating the underlying disease and reducing systemic inflammation, Secukinumab can normalize these cytokine levels, which in turn may lead to the "normalization" or increased activity of CYP450 enzymes.[1] This is not a direct drug-drug interaction but rather a drug-disease-drug interaction. This phenomenon could alter the metabolism of co-administered drugs that are CYP450 substrates, particularly those with a narrow therapeutic index such as warfarin or cyclosporine. Therefore, upon initiating or discontinuing Secukinumab in patients taking such medications, monitoring of the therapeutic effect (e.g., INR for warfarin) or drug concentration of the co-administered agent should be considered.[30]

Vaccines

• Live Vaccines: The administration of live vaccines is contraindicated during treatment with Secukinumab.[28] Because Secukinumab is an immunosuppressive agent, it can diminish the patient's ability to mount an effective immune response to a live attenuated virus or bacterium, potentially increasing the risk of a disseminated infection from the vaccine itself.[18] It is recommended that patients complete all age-appropriate immunizations according to current guidelines before commencing therapy.[21]
• Non-Live (Inactivated) Vaccines: Patients receiving Secukinumab may be given non-live or inactivated vaccines, such as the seasonal influenza or COVID-19 vaccines.[8] However, the immunosuppressive nature of the therapy may blunt the immune response to the vaccine, potentially reducing its efficacy. The clinical effectiveness of vaccination during Secukinumab treatment has not been fully established in dedicated trials.[47]

Other Biologics and Concomitant Medications

The co-administration of Secukinumab with other biologic agents has not been studied and is generally not recommended due to the potential for additive immunosuppression and a theoretically increased risk of serious infections. In clinical trials for psoriatic arthritis, Secukinumab has been shown to be effective both as monotherapy and when used in combination with methotrexate (MTX), a conventional synthetic disease-modifying antirheumatic drug (csDMARD).[1] No clinically significant pharmacokinetic interactions have been observed between Secukinumab and MTX.

Interacting Agent Class	Specific Examples	Potential Effect	Clinical Recommendation	Source(s)
CYP450 Substrates (Narrow Therapeutic Index)	Warfarin, Cyclosporine, Theophylline	Secukinumab may normalize CYP450 function by reducing inflammation, potentially altering the metabolism and concentration of the substrate drug.	Monitor therapeutic effect or concentration of the substrate drug upon initiation or discontinuation of Secukinumab.	1
Live Vaccines	MMR, Varicella (Chickenpox), Nasal Influenza Vaccine (FluMist), Yellow Fever	Increased risk of disseminated infection from the vaccine virus/bacterium due to immunosuppression.	Contraindicated during treatment. Complete all age-appropriate immunizations prior to initiating Secukinumab.	28
Non-Live (Inactivated) Vaccines	Inactivated Influenza Vaccine, Tdap, COVID-19 Vaccines	The immune response to the vaccine may be reduced, potentially leading to lower vaccine efficacy.	Non-live vaccines can be administered. The potential for a reduced immune response should be considered.	18
Table 8: Key Drug-Drug and Drug-Vaccine Interactions

Immunogenicity

Immunogenicity, the propensity of a therapeutic protein to elicit an immune response in the form of anti-drug antibodies (ADAs), is a critical consideration for all biologic therapies. High levels of ADAs, particularly neutralizing antibodies (NAbs), can lead to a loss of drug efficacy by clearing the drug from circulation or blocking its binding site, and can also be associated with hypersensitivity reactions.

Secukinumab has demonstrated a remarkably low immunogenicity profile, a significant clinical and commercial asset that is directly attributable to its fully human antibody structure.[43] In a large, pooled analysis of data from six pivotal Phase III clinical trials in patients with plaque psoriasis, involving 2,842 patients treated with Secukinumab for up to 52 weeks, the incidence of treatment-emergent ADAs (TE-ADAs) was exceptionally low. Only 11 patients (0.4%) developed TE-ADAs during the study period.[43]

Furthermore, of the patients who tested positive for ADAs, only a fraction developed antibodies with neutralizing capacity. Neutralizing antibodies were detected in just three of the nine evaluable patients with TE-ADAs.[43] Most importantly, the presence of either TE-ADAs or neutralizing antibodies was not associated with any discernible impact on the drug's clinical efficacy, its pharmacokinetic profile, or the emergence of any new safety concerns.[43] This very low rate of clinically relevant immunogenicity means that clinicians are less likely to encounter secondary loss of response due to antibody formation, making Secukinumab a more reliable and predictable long-term treatment option compared to biologics with higher rates of ADA development.

Clinical Evidence: Efficacy Across Approved Indications

The clinical development program for Secukinumab has been extensive, generating a robust body of evidence that supports its efficacy across a wide range of immune-mediated inflammatory diseases. The success of the program has not only established the drug as a standard of care but has also validated the IL-17A pathway as a central driver in these conditions. The progressive expansion of indications reflects a strategic approach, building upon foundational success in psoriasis to address related arthritides and other inflammatory disorders. A notable trend in the clinical trials is the use of high-bar efficacy endpoints, such as PASI 90/100 and complete resolution of enthesitis, signaling a shift in therapeutic goals from mere improvement to achieving disease clearance or minimal disease activity.

Plaque Psoriasis (PsO)

Secukinumab's first approval was for moderate-to-severe plaque psoriasis, and its efficacy in this indication is well-established through several large, randomized, placebo- and active-controlled Phase III trials.

• Pivotal Trials: The core evidence comes from the ERASURE (NCT01365455) and FIXTURE (NCT01358578) trials, supplemented by studies like FEATURE (NCT01555125).[3] These trials enrolled adults with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy.
• Efficacy Endpoints: The co-primary endpoints were the proportion of patients achieving at least a 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) and an Investigator's Global Assessment (IGA mod 2011) score of 0 (clear) or 1 (almost clear) at Week 12.
• Key Results: Secukinumab demonstrated rapid and profound efficacy.
• In the FIXTURE trial, which included an active comparator arm (etanercept, a TNF inhibitor), the PASI 75 response rate at Week 12 was 77.1% for Secukinumab 300 mg, compared to 67.0% for Secukinumab 150 mg, 44.0% for etanercept, and just 4.9% for placebo (all comparisons to placebo, P<0.001).[3]
• In the ERASURE trial, the PASI 75 response rate at Week 12 was 81.6% for Secukinumab 300 mg versus 4.5% for placebo (P<0.001).[3]
• The treatment effect is rapid, with a median time to achieve a 50% reduction in PASI score of approximately 3.0 weeks for the 300 mg dose, significantly faster than etanercept (7.0 weeks).[4]
• High-bar efficacy was also achieved, with PASI 90 response rates at Week 16 reaching approximately 80% in some studies, setting a new benchmark for clinical efficacy.[4]
• Long-term extension studies have confirmed that these high levels of efficacy are sustained, with durable responses maintained through five years of continuous treatment.[15]
• Pediatric PsO: Secukinumab is also approved for children aged 6 years and older. A dedicated pediatric study involving 162 children demonstrated superior efficacy over placebo, with approximately 80% of children treated with Secukinumab achieving PASI 75 at Week 12.[2]

Trial Name (Identifier)	Patient Population	Treatment Arms (Dose)	Primary Endpoint	Key Result (Drug vs. Placebo)	p-value	Source(s)
FIXTURE (NCT01358578)	Adults with moderate-to-severe PsO	Secukinumab 300 mg SC, Secukinumab 150 mg SC, Etanercept 50 mg SC, Placebo	PASI 75 at Week 12	77.1% (300 mg) vs. 4.9%	<0.001	3
ERASURE (NCT01365455)	Adults with moderate-to-severe PsO	Secukinumab 300 mg SC, Secukinumab 150 mg SC, Placebo	PASI 75 at Week 12	81.6% (300 mg) vs. 4.5%	<0.001	3
FEATURE (NCT01555125)	Adults with moderate-to-severe PsO (pre-filled syringe)	Secukinumab 300 mg SC, Secukinumab 150 mg SC, Placebo	PASI 75 at Week 12	75.9% (300 mg) vs. 0%	<0.0001	3
Table 4: Summary of Pivotal Phase III Efficacy Outcomes in Plaque Psoriasis

Psoriatic Arthritis (PsA)

Following its success in psoriasis, Secukinumab was developed for psoriatic arthritis, a condition that affects both the skin and joints.

• Pivotal Trials: The comprehensive FUTURE clinical trial program, including FUTURE 1 (NCT01392326), FUTURE 2 (NCT01752634), and FUTURE 5, established its efficacy in patients with active PsA, including those who were biologic-naïve and those who had an inadequate response to TNF inhibitors (anti-TNF-IR).[3]
• Efficacy Endpoints: The primary endpoint was typically the proportion of patients achieving at least a 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 16 or Week 24.
• Key Results: Secukinumab demonstrated significant improvements across the key domains of PsA.
• In the FUTURE 2 trial, the ACR20 response rate at Week 24 was 54% for the 300 mg dose and 51% for the 150 mg dose, compared to only 15% for placebo (P<0.0001 for both).[3]
• The drug showed marked efficacy in resolving enthesitis and dactylitis ("sausage digits"), which are hallmark and often difficult-to-treat features of PsA.[13] In FUTURE 5, complete resolution of enthesitis was seen in 56% of patients on the 300 mg dose versus 35% on placebo.[13]
• For patients with coexistent psoriasis, Secukinumab provided substantial skin clearance, with PASI 90 achieved by 54% of patients on 300 mg versus 9% on placebo in the FUTURE 5 trial.[13]
• Long-term data from the FUTURE program and real-world studies like SERENA show high rates of drug survival and sustained efficacy over 3 to 5 years, with favorable safety profiles.[13]
• Pediatric PsA (JPsA): Secukinumab is approved for children aged 2 years and older with active JPsA. Evidence from a pediatric study showed that patients treated with Secukinumab had significantly fewer disease flare-ups compared to those who were switched to placebo.[10]

Trial Name (Identifier)	Patient Population	Treatment Arms (Dose)	Primary Endpoint	Key Result (Drug vs. Placebo)	p-value	Source(s)
FUTURE 2 (NCT01752634)	Adults with active PsA	Secukinumab 300 mg SC, 150 mg SC, 75 mg SC, Placebo	ACR20 at Week 24	54% (300 mg) vs. 15%	<0.0001	3
FUTURE 1 (NCT01392326)	Adults with active PsA	Secukinumab 10 mg/kg IV loading, then 150 mg or 75 mg SC, Placebo	ACR20 at Week 24	50.0% (150 mg) vs. 17.3%	<0.001	3
FUTURE 5	Adults with active PsA (biologic-naïve and anti-TNF-IR)	Secukinumab 300 mg SC, 150 mg SC, Placebo	ACR20 at Week 16	63% (300 mg) vs. 27%	<0.0001	13
Table 5: Summary of Pivotal Phase III Efficacy Outcomes in Psoriatic Arthritis

Axial Spondyloarthropathies (AS and nr-axSpA)

Secukinumab has become a cornerstone therapy for axial spondyloarthropathies, a group of inflammatory diseases primarily affecting the spine and sacroiliac joints.

• Pivotal Trials: The MEASURE program (including MEASURE 1, 2, and 4) established efficacy in active ankylosing spondylitis (also known as radiographic axSpA).[3] The PREVENT trial established efficacy in active non-radiographic axial spondyloarthritis (nr-axSpA).
• Efficacy Endpoints: The primary endpoint was typically the proportion of patients achieving at least a 20% or 40% improvement in the Assessment of SpondyloArthritis international Society criteria (ASAS20 or ASAS40) at Week 16.
• Key Results:
• In the MEASURE 2 trial for AS, the ASAS20 response rate at Week 16 was 61.1% for the 150 mg dose, compared to 28.4% for placebo (P<0.0001).[3]
• For nr-axSpA, Secukinumab demonstrated significant improvement over placebo in patients who had objective signs of inflammation (i.e., elevated C-reactive protein and/or evidence of sacroiliitis on MRI) but lacked definitive radiographic damage.[2] In the PREVENT trial, 41% of patients on Secukinumab achieved ASAS40 at Week 16 versus 29% on placebo.[52]
• Long-term data from the MEASURE program and real-world evidence confirm that the clinical responses are sustained for up to 5 years, with high drug retention rates and a consistent safety profile.[54]
• Intravenous Formulation: The development and approval of an intravenous formulation in October 2023 was a strategic move to provide an alternative administration route for patients with rheumatic diseases.[2] This allows Secukinumab to compete in infusion center settings and cater to patient or physician preference. Phase III trials like INVIGORATE-1 (NCT04156620) confirmed that the IV route (6 mg/kg loading dose followed by 3 mg/kg q4w) was effective and safe for treating active axSpA.[14]

Trial Name (Identifier)	Patient Population	Treatment Arms (Dose)	Primary Endpoint	Key Result (Drug vs. Placebo)	p-value	Source(s)
MEASURE 2 (NCT01649375)	Adults with active AS	Secukinumab 150 mg SC, 75 mg SC, Placebo	ASAS20 at Week 16	61.1% (150 mg) vs. 28.4%	<0.0001	3
MEASURE 1 (NCT01358175)	Adults with active AS	Secukinumab IV loading, then 150 mg or 75 mg SC, Placebo	ASAS20 at Week 16	60.8% (150 mg) vs. 28.7%	<0.01	3
INVIGORATE-1 (NCT04156620)	Adults with active axSpA (r-axSpA and nr-axSpA)	Secukinumab IV, Placebo IV	ASAS40 at Week 16	40.9% vs. 22.9%	<0.0001	14
Table 6: Summary of Pivotal Phase III Efficacy Outcomes in Spondyloarthropathies

Hidradenitis Suppurativa (HS)

In 2023, Secukinumab became the first new biologic therapy approved for moderate-to-severe hidradenitis suppurativa in nearly a decade, addressing a significant unmet need for this chronic, painful, and scarring skin disease.[11]

• Pivotal Trials: Approval was based on the results of two identical Phase III trials, SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).[59]
• Efficacy Endpoint: The primary endpoint was the Hidradenitis Suppurativa Clinical Response (HiSCR), defined as at least a 50% reduction in the total abscess and inflammatory nodule count with no increase in the number of abscesses or draining tunnels, at Week 16.
• Key Results: Both trials met their primary endpoint, demonstrating that a significantly higher proportion of adult patients with moderate-to-severe HS treated with Secukinumab 300 mg (administered every 2 or 4 weeks) achieved a HiSCR at Week 16 compared to those on placebo.[52] This approval validated the role of IL-17A in the pathology of HS and provided a much-needed new therapeutic option for patients.

Enthesitis-Related Arthritis (ERA)

Secukinumab is approved for active enthesitis-related arthritis in pediatric patients aged 4 years and older.[1] ERA is a category of Juvenile Idiopathic Arthritis (JIA) that is considered a pediatric precursor to adult spondyloarthropathies, sharing a common pathogenic link to the IL-17 pathway. Approval was based on a study demonstrating that children treated with Secukinumab experienced significantly fewer disease flare-ups compared to those randomized to placebo, confirming its efficacy in this younger population.[52]

Comprehensive Safety Profile

The safety profile of Secukinumab has been extensively evaluated in a large clinical development program spanning multiple indications and in post-marketing surveillance, establishing it as a generally well-tolerated long-term therapy. The pattern of adverse events is largely predictable based on the drug's mechanism of action—the targeted inhibition of IL-17A.

Overview of Adverse Events (AEs)

The overall safety profile is consistent across its approved indications.[46] In long-term observational studies, the incidence of adverse events tends to be highest within the first six months of treatment and then decreases and remains stable over time.[55]

• Very Common AEs (>10% incidence): The most frequently reported adverse events are upper respiratory tract infections (URTIs), primarily nasopharyngitis (common cold symptoms).[2]
• Common AEs (1% to 10% incidence): Other common events include diarrhea, oral herpes (cold sores), and rhinorrhea (runny nose).[2] Mild-to-moderate injection site reactions, such as redness, itching, or swelling, are also common but rarely lead to treatment discontinuation.[2]
• Hepatotoxicity: In pre-marketing trials and post-marketing surveillance, Secukinumab has not been linked to idiosyncratic, clinically apparent liver injury.[46] However, as an immunomodulator, it carries a risk of reactivating latent hepatitis B virus (HBV) in susceptible carriers. Therefore, screening for HBV is recommended, and prophylactic antiviral therapy may be necessary for at-risk patients to prevent reactivation.[46]

Warnings and Precautions

The product label for Secukinumab includes several important warnings and precautions that clinicians and patients must be aware of.

Infections

The most significant risk associated with Secukinumab is an increased susceptibility to infections, which is a direct consequence of its mechanism of action.[17] IL-17A plays a vital role in host defense, particularly in maintaining mucosal barrier integrity and orchestrating the immune response against fungal and certain bacterial pathogens.[5]

• General Risk: Clinical trials have consistently shown a higher rate of infections in patients treated with Secukinumab compared to placebo.[13] While most of these are mild-to-moderate URTIs, serious infections have occurred, and in rare cases, have been fatal.[18] Caution is warranted when considering Secukinumab for patients with a chronic infection or a history of recurrent infections.[20]
• Mucocutaneous Candidiasis: Consistent with the role of IL-17A in antifungal immunity, there is a dose-dependent increase in the risk of mucocutaneous candidiasis (e.g., oral thrush, esophageal or vulvovaginal candidiasis).[13] These infections are typically mild to moderate and respond to standard antifungal treatment without necessitating discontinuation of Secukinumab.
• Tuberculosis (TB): Before initiating therapy, all patients must be evaluated for active or latent TB infection.[18] Secukinumab should not be administered to patients with active TB. If latent TB is detected, treatment for TB should be initiated prior to starting Secukinumab.[21] Patients should be monitored for signs and symptoms of TB during and after treatment.

Inflammatory Bowel Disease (IBD)

The role of IL-17 in the gut is complex and context-dependent; while it can be pathogenic, it can also play a protective role in maintaining gut mucosal integrity. Blocking IL-17A can disrupt this balance.

• Risk: Cases of new-onset or exacerbations of existing IBD (both Crohn's disease and ulcerative colitis) have been observed in clinical trials with Secukinumab.[2] Some of these cases were serious.
• Management: Caution should be exercised when prescribing Secukinumab to patients with a known history of IBD. All patients should be monitored for the emergence or worsening of IBD symptoms, such as abdominal pain, diarrhea, or blood in the stool, during treatment.[2]

Hypersensitivity Reactions

• Risk: As with all protein-based therapeutics, there is a risk of hypersensitivity reactions. Serious reactions, including rare cases of anaphylaxis and angioedema, have been reported with Secukinumab.[2]
• Management: If a serious allergic reaction occurs, Secukinumab must be discontinued immediately, and appropriate emergency medical treatment should be initiated.[47]

Latex Allergy

• The removable needle caps of the Cosentyx Sensoready® pen and the 150 mg/mL and 75 mg/0.5 mL prefilled syringes contain a derivative of natural rubber latex.[18] These presentations should not be handled by individuals with a latex sensitivity. The UnoReady® pen is designed with a cap that is not made with natural rubber latex, providing an alternative for these patients.[60]

Contraindications

The only absolute contraindication for Secukinumab is a history of a previous serious hypersensitivity reaction to the active substance, secukinumab, or to any of the excipients in the formulation.[13]

Use in Special Populations

• Pregnancy: There are no adequate and well-controlled studies of Secukinumab in pregnant women. Animal reproduction studies did not reveal evidence of harm to the fetus. The FDA advises that the drug should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The EMA recommends that women of childbearing potential should use effective contraception during treatment and for at least 20 weeks after the last dose.[2]
• Lactation: It is not known whether Secukinumab is excreted in human milk or absorbed systemically after ingestion by a nursing infant. Because many drugs are excreted in human milk, caution should be exercised when administering to a breastfeeding woman.[18]
• Geriatric Use: Clinical trials did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. No overall differences in safety or efficacy were observed, but the data are limited.[47]

Comparative Safety and Lack of Black Box Warning

A significant feature of Secukinumab's safety profile is the absence of an FDA-issued "black box warning".[13] The FDA reserves this type of warning for drugs with the most serious or life-threatening risks. This "non-finding" is a powerful differentiator that shapes clinical perception and prescribing behavior. It contrasts sharply with another drug in the IL-17 inhibitor class, the IL-17

receptor antagonist brodalumab (Siliq), which carries a black box warning for suicidal ideation and behavior observed in its clinical trials.[22] Although a causal relationship for brodalumab was not definitively established, the warning imposes a significant clinical and administrative burden, including a restricted access program (REMS). The absence of such a warning for Secukinumab gives it a substantial advantage, making it a more straightforward choice for clinicians, particularly when treating patients with a history of depression or other mental health conditions.

System Organ Class	Adverse Event	Frequency	Clinical Context/Comments	Source(s)
Infections and Infestations	Upper Respiratory Tract Infection (Nasopharyngitis)	Very Common (>10%)	Most frequent AE; typically mild to moderate.	2
	Mucocutaneous Candidiasis (Oral, Esophageal, Vulvovaginal)	Common (1-10%)	Dose-dependent risk. Consistent with MOA. Usually manageable with standard antifungals.	13
	Herpes Simplex (Oral)	Common (1-10%)	Reactivation of latent virus.	2
	Tuberculosis (Reactivation)	Rare (<1%)	Pre-treatment screening for latent/active TB is mandatory.	20
Gastrointestinal Disorders	Diarrhea	Common (1-10%)	Usually mild and transient.	2
	Inflammatory Bowel Disease (New Onset or Exacerbation)	Uncommon (<1%)	A key warning. Caution in patients with a history of IBD. Monitor for new/worsening symptoms.	18
Immune System Disorders	Hypersensitivity Reactions (Urticaria, Anaphylaxis)	Rare (<1%)	Anaphylaxis is a contraindication to future use. Discontinue immediately if serious reaction occurs.	18
Skin and Subcutaneous Tissue Disorders	Injection Site Reactions	Common (1-10%)	Typically mild erythema, pruritus, or swelling.	2
Hepatobiliary Disorders	Hepatitis B Reactivation	Rare (<1%)	Can occur in susceptible carriers. Screening and potential prophylaxis are recommended.	46
Table 7: Comprehensive Safety Profile and Adverse Event Frequencies

Dosage, Administration, and Practical Considerations

The dosing and administration of Secukinumab are highly specific and tailored to the indication, patient age, and in some cases, body weight. The availability of multiple formulations and dosing strategies provides flexibility for clinicians to optimize treatment for individual patients.

Dosing Regimens by Indication

Secukinumab regimens typically consist of an initial weekly "loading" phase to rapidly achieve therapeutic concentrations, followed by a less frequent "maintenance" phase.

• Plaque Psoriasis (Adults): The recommended subcutaneous (SC) dose is 300 mg administered at Weeks 0, 1, 2, 3, and 4, followed by a maintenance dose of 300 mg every 4 weeks. Each 300 mg dose can be given as a single 300 mg injection (UnoReady® pen) or as two separate 150 mg injections. For some patients, a 150 mg dose may be considered acceptable.[20]
• Plaque Psoriasis (Pediatric, ≥6 years): Dosing is based on body weight. For patients weighing less than 50 kg, the recommended dose is 75 mg SC. For patients weighing 50 kg or more, the dose is 150 mg SC. The administration schedule is the same as for adults: Weeks 0, 1, 2, 3, 4, and then every 4 weeks.[49]
• Psoriatic Arthritis (Adults):
• Subcutaneous (SC) Route: For patients with coexistent moderate-to-severe plaque psoriasis, the 300 mg psoriasis regimen is recommended. For other PsA patients, treatment can be initiated with or without a loading dose. The loading regimen is 150 mg SC at Weeks 0, 1, 2, 3, and 4, followed by 150 mg every 4 weeks. The non-loading regimen is 150 mg SC every 4 weeks. If a patient has a persistent active disease, the dose can be increased to 300 mg every 4 weeks.[20]
• Intravenous (IV) Route: An alternative for adults, administered by a healthcare professional. The loading dose is 6 mg/kg infused at Week 0, followed by a maintenance dose of 1.75 mg/kg infused every 4 weeks. A non-loading regimen of 1.75 mg/kg every 4 weeks is also an option.[63]
• Ankylosing Spondylitis & Non-Radiographic Axial Spondyloarthritis (Adults):
• Subcutaneous (SC) Route: The dosing is the same as for PsA (without coexistent psoriasis). It can be given with a loading dose (150 mg weekly for 5 weeks, then 150 mg every 4 weeks) or without (150 mg every 4 weeks). The dose may be increased to 300 mg every 4 weeks for AS patients with an inadequate response.[20]
• Intravenous (IV) Route: The dosing regimen is identical to that for PsA.[63]
• Hidradenitis Suppurativa (Adults): The recommended SC dose is 300 mg at Weeks 0, 1, 2, 3, and 4, followed by 300 mg every 4 weeks. For patients with an inadequate response, the maintenance dosing frequency can be increased to every 2 weeks.[49]
• Juvenile Psoriatic Arthritis (JPsA, ≥2 years) & Enthesitis-Related Arthritis (ERA, ≥4 years): Dosing is subcutaneous and weight-based. For patients weighing 15 kg to less than 50 kg, the dose is 75 mg. For those weighing 50 kg or more, the dose is 150 mg. The schedule is Weeks 0, 1, 2, 3, 4, followed by every 4 weeks.[49]

Indication (Population)	Route	Loading Dose	Maintenance Dose	Key Notes
Plaque Psoriasis (Adult)	SC	300 mg at Weeks 0, 1, 2, 3, 4	300 mg every 4 weeks	150 mg dose may be acceptable for some.
Plaque Psoriasis (Pediatric, ≥6 yrs)	SC	Weeks 0, 1, 2, 3, 4	Every 4 weeks	Weight-based: <50 kg: 75 mg; ≥50 kg: 150 mg.
Psoriatic Arthritis (Adult)	SC	Optional: 150 mg at Weeks 0, 1, 2, 3, 4	150 mg every 4 weeks	Can increase to 300 mg. Use 300 mg regimen for coexistent mod-sev PsO.
	IV	Optional: 6 mg/kg at Week 0	1.75 mg/kg every 4 weeks	Administered over 30 min by HCP.
Ankylosing Spondylitis (Adult)	SC	Optional: 150 mg at Weeks 0, 1, 2, 3, 4	150 mg every 4 weeks	Can increase to 300 mg if response is inadequate.
	IV	Optional: 6 mg/kg at Week 0	1.75 mg/kg every 4 weeks	Administered over 30 min by HCP.
nr-axSpA (Adult)	SC	Optional: 150 mg at Weeks 0, 1, 2, 3, 4	150 mg every 4 weeks	-
	IV	Optional: 6 mg/kg at Week 0	1.75 mg/kg every 4 weeks	Administered over 30 min by HCP.
Hidradenitis Suppurativa (Adult)	SC	300 mg at Weeks 0, 1, 2, 3, 4	300 mg every 4 weeks	Can increase frequency to every 2 weeks if needed.
JPsA (≥2 yrs) & ERA (≥4 yrs)	SC	Weeks 0, 1, 2, 3, 4	Every 4 weeks	Weight-based: 15-<50 kg: 75 mg; ≥50 kg: 150 mg.
Table 3: Dosing and Administration Regimens by Indication

Administration Instructions

Proper administration technique is crucial for ensuring efficacy and minimizing local reactions.

• Patient Training: Secukinumab is intended for use under the guidance of a physician. For SC administration, patients or their caregivers may self-inject using the pre-filled syringe or auto-injector pen after receiving proper training on the correct injection technique.[20]
• Preparation: The injection device should be removed from the refrigerator and allowed to warm to room temperature for 15-30 minutes (for 150 mg devices) or 30-45 minutes (for 300 mg devices) before use. This helps reduce discomfort during injection. The device should not be shaken.[20]
• Injection Sites: The recommended SC injection sites are the front of the thighs, the abdomen (avoiding the 2-inch area around the navel), and the outer upper arms (if given by a caregiver). Injection sites must be rotated with each administration. Injections should never be given into skin that is tender, bruised, red, hard, scarred, or affected by psoriasis.[19]
• Healthcare Professional Administration: The lyophilized powder for reconstitution and the intravenous formulation are for administration by healthcare professionals only. The IV infusion is typically administered over a period of 30 minutes.[20]

Practical Considerations

• Storage: Secukinumab must be stored in a refrigerator at a temperature between 2°C and 8°C (36°F to 46°F). It should be kept in its original carton to protect it from light. It must not be frozen.[19]
• Pre-treatment Assessment: Before initiating therapy, clinicians must evaluate patients for tuberculosis infection.[20] For pediatric patients, it is important to ensure that all age-appropriate vaccinations are up-to-date before starting treatment.[18]
• Monitoring: While routine laboratory monitoring is not required by the label [13], clinicians should remain vigilant for signs and symptoms of infection (especially URTIs and candidiasis), new or worsening IBD, and hypersensitivity reactions. For patients on concomitant narrow therapeutic index drugs (e.g., warfarin), monitoring the effects of that drug may be warranted upon initiation or cessation of Secukinumab.[30]

Regulatory and Commercial Landscape

Manufacturer and Development

Secukinumab was discovered, developed, and is manufactured by the global pharmaceutical company Novartis.[2] During its development phase, it was identified by the research code AIN457.[3] It is marketed worldwide under the proprietary brand name Cosentyx®.[1]

Regulatory Approval History

The regulatory journey of Secukinumab showcases a highly successful and strategic clinical development program, marked by a steady expansion of approved indications following its initial launch. This phased approach allowed Novartis to build a massive evidence base, gain clinician familiarity, and systematically broaden the drug's market.

U.S. Food and Drug Administration (FDA)

The FDA approval timeline demonstrates a logical progression from a large primary indication to related diseases and special populations:

• January 21, 2015: Initial approval was granted for the treatment of moderate-to-severe plaque psoriasis in adults, making it the first IL-17A inhibitor to enter the market.[11]
• January 15, 2016: The label was expanded to include two major rheumatic diseases: active psoriatic arthritis (PsA) and active ankylosing spondylitis (AS) in adults.[2]
• June 16, 2020: Approval was granted for active non-radiographic axial spondyloarthritis (nr-axSpA) in adults with objective signs of inflammation.[11]
• June 1, 2021: The first pediatric indication was approved for moderate-to-severe plaque psoriasis in patients aged 6 years and older.[11]
• December 22, 2021: The pediatric label was further expanded to include active enthesitis-related arthritis (ERA) in patients ≥4 years and active juvenile psoriatic arthritis (JPsA) in patients ≥2 years.[11]
• October 6, 2023: A new intravenous (IV) formulation was approved for adults with PsA, AS, and nr-axSpA, offering an alternative route of administration.[2]
• October 31, 2023: A significant new indication was approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) in adults, addressing a high unmet need.[11]

European Medicines Agency (EMA)

The EMA's approval history has largely paralleled the FDA's, establishing Secukinumab as a key therapy across Europe:

• January 15, 2015: Received its first marketing authorization valid throughout the European Union for the treatment of moderate-to-severe plaque psoriasis in adults.[2]
• Subsequent approvals for PsA, AS, and nr-axSpA followed, mirroring the US approvals.[52]
• June 1, 2023: The European Commission approved Secukinumab for the treatment of active moderate-to-severe hidradenitis suppurativa in adults, making it the first IL-17A inhibitor approved for this indication in Europe.[59]
• Pediatric indications for psoriasis and juvenile idiopathic arthritis have also been approved.[52]

Indication	Patient Population	Approving Agency	Date of First Approval for Indication
Plaque Psoriasis	Adults (moderate-to-severe)	FDA / EMA	Jan 2015
Psoriatic Arthritis	Adults (active)	FDA / EMA	Jan 2016
Ankylosing Spondylitis	Adults (active)	FDA / EMA	Jan 2016
Non-Radiographic Axial Spondyloarthritis	Adults (active, with objective signs of inflammation)	FDA / EMA	Jun 2020 (FDA)
Plaque Psoriasis (Pediatric)	≥6 years (moderate-to-severe)	FDA / EMA	Jun 2021 (FDA)
Enthesitis-Related Arthritis (Pediatric)	≥4 years (active)	FDA / EMA	Dec 2021 (FDA)
Juvenile Psoriatic Arthritis (Pediatric)	≥2 years (active)	FDA / EMA	Dec 2021 (FDA)
Hidradenitis Suppurativa	Adults (moderate-to-severe)	EMA / FDA	Jun 2023 (EMA) / Oct 2023 (FDA)
Intravenous Formulation	Adults (PsA, AS, nr-axSpA)	FDA	Oct 2023
Table 2: Summary of Key FDA and EMA Approved Indications

Market Context and Competition

As the first-in-class IL-17A inhibitor, Secukinumab enjoyed a significant first-to-market advantage, allowing it to establish a strong foothold with clinicians and patients.[2] Its commercial success has been substantial, with over 5.2 million prescriptions filled in the U.S. by late 2024, making it a blockbuster product for Novartis.[16]

The success of Secukinumab has also validated the IL-17 pathway as a highly lucrative therapeutic target, which has spurred intense competition. The market now includes several other biologics that target the same pathway, creating a highly competitive landscape. Key competitors include:

• Other IL-17 Inhibitors: Ixekizumab (Taltz) from Eli Lilly, which also targets IL-17A, and Brodalumab (Siliq) from Valeant, which targets the IL-17 receptor.
• IL-23 Inhibitors: A class of biologics that work "upstream" of IL-17 by inhibiting IL-23, a key cytokine for Th17 cell development. This class includes drugs like Guselkumab (Tremfya), Risankizumab (Skyrizi), and Tildrakizumab.

In this crowded market, differentiation is based on multiple factors, including efficacy (speed of onset, depth of response, durability), safety (particularly the IBD risk and the presence or absence of black box warnings), dosing convenience (subcutaneous vs. intravenous, dosing frequency), and the breadth of approved indications. Secukinumab's continued investment in clinical trials and indication expansion is a core strategy to maintain its competitive leadership.

Conclusion

Secukinumab (Cosentyx®) has established itself as a transformative therapy in the field of immunology. As the first-in-class selective IL-17A inhibitor, it offers a highly targeted mechanism of action that has proven to be exceptionally effective across a broad and expanding range of chronic immune-mediated inflammatory diseases. Its molecular design as a fully human monoclonal antibody translates into a clinically significant low immunogenicity profile, contributing to its reliable and durable long-term efficacy.

The extensive clinical trial program has consistently demonstrated rapid and profound improvements in the signs and symptoms of plaque psoriasis, psoriatic arthritis, axial spondyloarthropathies, and hidradenitis suppurativa, setting new benchmarks for therapeutic success in these conditions. The drug's safety profile is well-characterized and considered favorable, with the most common adverse events being a predictable consequence of its targeted immunomodulation. The absence of an FDA black box warning further strengthens its risk-benefit proposition for clinicians and patients.

Supported by a favorable pharmacokinetic profile that allows for convenient monthly maintenance dosing and a strategic expansion into pediatric populations and new formulations, Secukinumab stands as a cornerstone of modern therapy for IL-17A-driven diseases. Its journey from a novel molecular target to a multi-indication blockbuster therapeutic exemplifies the success of rational drug design and targeted immunotherapy in modern medicine.

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