Amlitelimab (SAR445229): A Comprehensive Clinical and Strategic Analysis of a First-in-Class OX40 Ligand Inhibitor

Executive Summary

Amlitelimab (SAR445229) is an investigational, fully human, non-depleting monoclonal antibody poised to establish a new therapeutic class as a first-in-class inhibitor of the OX40 ligand (OX40L). Developed by Sanofi following its strategic acquisition of Kymab Ltd., Amlitelimab represents a significant advancement in immunomodulatory therapy, with its primary development focus on moderate-to-severe atopic dermatitis (AD). Its novel mechanism of action, which involves targeting an upstream co-stimulatory pathway critical for T-cell activation and memory, distinguishes it from existing treatments that target more downstream inflammatory mediators. By binding to OX40L on antigen-presenting cells, Amlitelimab blocks the activation of multiple T-helper cell subsets (Th2, Th1, Th17, and Th22) implicated in AD pathogenesis. Critically, this approach spares regulatory T-cells, suggesting a potential to restore immune homeostasis rather than inducing broad immunosuppression.

The clinical development program has yielded compelling evidence of Amlitelimab's efficacy and a favorable safety profile. The pivotal Phase IIb STREAM-AD study in adults with moderate-to-severe AD met its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in skin lesions and pruritus across all doses tested. The most profound finding from this trial was the unprecedented durable response observed in patients after treatment cessation; a majority of clinical responders maintained significant improvements for at least 28 weeks off-drug. This durable effect is supported by biomarker data showing sustained suppression of key inflammatory mediators long after the drug was withdrawn, lending credence to its potential for long-term disease modification.

These findings have directly informed the design of the comprehensive Phase III OCEANA program, which is evaluating a quarterly (every 12-week) maintenance dosing regimen—a potential paradigm shift that would offer a substantial convenience and adherence advantage over current bi-weekly or monthly biologics. The safety profile of Amlitelimab has been consistently well-tolerated across trials, with an adverse event profile comparable to placebo and a notable absence of specific side effects associated with other systemic AD therapies, such as conjunctivitis or the class-based risks of JAK inhibitors.

Strategically, Amlitelimab is positioned to address significant unmet needs in the AD market. Its unique combination of a novel, upstream mechanism, broad-spectrum efficacy across inflammatory pathways, potential for a quarterly dosing schedule, and a clean safety profile provides a powerful multi-faceted value proposition. It is positioned not only as a potent first-line systemic option but also as a potential therapy for patients who have had an inadequate response to existing biologics or JAK inhibitors. As the first-in-class OX40L inhibitor, Amlitelimab is a priority asset for Sanofi with blockbuster potential, capable of challenging the current standard of care and redefining long-term management for patients with atopic dermatitis and potentially a range of other immune-mediated inflammatory diseases.

Introduction to Amlitelimab: A Novel Immunomodulator

The therapeutic landscape for immune-mediated inflammatory diseases is undergoing a period of rapid innovation, driven by a deeper understanding of the complex cellular and molecular pathways that underpin chronic inflammation. Within this context, Amlitelimab has emerged as a highly anticipated investigational agent, representing a strategic shift towards targeting upstream regulatory checkpoints in the immune cascade. Its development is focused on addressing the significant unmet medical needs of patients with conditions like atopic dermatitis, where existing therapies, while effective, may be limited by dosing frequency, incomplete response, or long-term safety concerns.

Drug Profile and Classification

Amlitelimab, also identified by the development codes SAR445229 and KY1005, is a fully human immunoglobulin G4 (IgG4) monoclonal antibody.[1] It is engineered to be non-cytotoxic and non-depleting, meaning it modulates immune function without destroying target cells.[1] Its therapeutic classification is that of an immunomodulatory drug, belonging to a new class of agents known as OX40 ligand (OX40L) inhibitors.[4] As a biologic therapy, it is formulated as a solution for both subcutaneous (SC) and intravenous (IV) administration, though SC is the primary route for late-stage development in atopic dermatitis.[6] The U.S. Adopted Names (USAN) Council and the World Health Organization (WHO) have officially designated its generic name as Amlitelimab, and it is recognized as a New Molecular Entity (NME).[5]

Table 1: Amlitelimab - Key Drug Characteristics

Attribute	Description
Generic Name	Amlitelimab
Code Names	SAR445229, KY1005
Drug Class	Monoclonal antibody (fully human IgG4); Immunomodulator; OX40 ligand inhibitor
Mechanism of Action	Binds to OX40 Ligand (OX40L) on antigen-presenting cells, blocking its interaction with the OX40 receptor on T-cells
Key Attributes	Non-cytotoxic, non-T-cell depleting
Originator	Kymab Ltd.
Current Developer	Sanofi
Lead Indication (Highest Phase)	Atopic Dermatitis (Phase III)
Administration Route	Subcutaneous (SC), Intravenous (IV)

Development History and Strategic Context

Amlitelimab was originally discovered and developed by Kymab Ltd., a UK-based biopharmaceutical company, utilizing its proprietary Kymouse™ platform for creating fully human monoclonal antibodies.[4] The promise of this novel asset attracted significant industry attention, culminating in its acquisition by the global pharmaceutical company Sanofi in 2021.[9] The transaction was a major strategic investment for Sanofi, involving an upfront payment of $1.1 billion and potential future milestone payments of up to $350 million.[10]

This acquisition was not merely an opportunistic pipeline addition but a cornerstone of Sanofi's declared strategy to build and sustain leadership in the immunology sector.[3] Sanofi, the developer of the blockbuster IL-4/IL-13 inhibitor dupilumab (Dupixent), already holds a dominant position in the atopic dermatitis market.[12] The substantial investment in Amlitelimab signals a forward-looking strategy to innovate beyond its existing successes. By embracing a molecule with a fundamentally different, upstream mechanism of action, Sanofi is proactively developing a therapy that could succeed its own market leader, address patient populations with different underlying inflammatory drivers (e.g., non-Type 2 inflammation), and mitigate long-term risks associated with patent expirations. Sanofi has publicly identified Amlitelimab as one of its priority pipeline assets, projecting potential peak sales to exceed €5 billion, a figure that underscores the company's confidence in its potential to become a first- or best-in-class treatment for a range of chronic inflammatory diseases.[11]

Pharmacology and Mechanism of Action: Targeting the OX40-OX40L Axis

The therapeutic rationale for Amlitelimab is rooted in the targeted modulation of the OX40-OX40 Ligand (OX40L) signaling axis, a key co-stimulatory pathway that governs the activation, proliferation, and survival of T-cells. This pathway has been identified as a critical driver in the pathogenesis of atopic dermatitis and other chronic inflammatory disorders.

The Pathophysiology of Atopic Dermatitis and the Role of the OX40-OX40L Pathway

Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease characterized by intense pruritus, eczematous lesions, and a chronic, relapsing course.[15] Its pathophysiology is complex, involving a dysfunctional skin barrier and a dysregulated immune response.[2] While Type 2 inflammation, driven by T-helper 2 (Th2) cells and their associated cytokines (e.g., IL-4, IL-13, IL-31), has been a primary focus of recent therapeutic development, it is now understood that non-Type 2 pathways involving Th1, Th17, and Th22 cells also contribute significantly to the disease's chronicity and clinical presentation.[2]

The OX40-OX40L axis functions as a critical "accelerator" for T-cell-mediated immune responses.[2] Following initial T-cell activation by an antigen-presenting cell (APC), such as a dendritic cell, OX40L is upregulated on the surface of the APC, while its cognate receptor, OX40 (also known as CD134), becomes expressed on the activated T-cell.[1] The engagement of OX40L with OX40 delivers a potent secondary co-stimulatory signal to the T-cell. This signal is essential for sustaining the immune response; it promotes the clonal expansion and long-term survival of effector T-cells, enhances their production of pro-inflammatory cytokines, and facilitates the generation of long-lived memory T-cells that contribute to disease flares and chronicity.[2] By amplifying the activity of multiple effector T-cell lineages (Th2, Th1, Th17, Th22), the OX40-OX40L pathway acts as a central node in perpetuating the cycle of inflammation that defines moderate-to-severe AD.[15]

Amlitelimab's Novel Mechanism: Selective Inhibition of OX40 Ligand

Amlitelimab intervenes at this critical juncture by acting as a high-affinity antagonist of OX40L.[1] As a fully human

IgG4 monoclonal antibody, it is designed to specifically bind to the OX40L protein expressed on the surface of APCs.[1] This binding physically obstructs the interaction between OX40L and the OX40 receptor on T-cells, effectively preventing the delivery of the co-stimulatory signal.[2] By blocking this "upstream" event in the T-cell activation cascade, Amlitelimab can broadly inhibit the downstream inflammatory consequences mediated by multiple T-cell subsets, addressing both Type 2 and non-Type 2 inflammation.[1]

The decision to target OX40L on APCs, rather than the OX40 receptor on T-cells, represents a sophisticated and deliberate immunological strategy. This approach is mechanistically distinct from other agents in development, such as rocatinlimab, which target the OX40 receptor and lead to the depletion of activated T-cells.[2] Amlitelimab's mechanism is non-depleting and, crucially, spares a vital subset of T-cells known as regulatory T-cells (Tregs).[17] Tregs express the OX40 receptor but are essential for maintaining immune tolerance and actively suppressing excessive inflammatory responses. By leaving the Treg population intact, Amlitelimab's mechanism is designed not simply to suppress inflammation but to help restore a natural state of immune homeostasis—a balance between pro-inflammatory effector cells and anti-inflammatory regulatory cells.[2] This preservation of the immune system's regulatory arm is believed to be the biological foundation for the durable, off-drug clinical responses observed in clinical trials, suggesting a potential for true disease modification rather than continuous pharmacological suppression. Furthermore, research indicates that Amlitelimab may also block T-cell independent pro-inflammatory activity by inhibiting "OX40L back signaling" within the APC itself, adding another layer to its immunomodulatory effects.[2]

Comprehensive Clinical Development Program

Sanofi has initiated a robust and large-scale clinical development program to rigorously evaluate the efficacy, safety, and unique therapeutic potential of Amlitelimab. The program, particularly for its lead indication of atopic dermatitis, is strategically designed to establish its profile in diverse patient populations and treatment settings, culminating in the comprehensive Phase III OCEANA program.

Overview of Clinical Strategy: The OCEANA Program

The cornerstone of Amlitelimab's late-stage development in atopic dermatitis is the OCEANA program, a series of interconnected Phase III global trials.[16] This program was designed based on the highly encouraging results from the Phase IIa and IIb studies, which not only confirmed the drug's efficacy but also revealed its potential for a durable response after treatment withdrawal.[18] A central goal of the OCEANA program is therefore to confirm these findings in a larger patient population and formally investigate the viability of an extended dosing interval, specifically an every-12-week (Q12W) subcutaneous maintenance regimen.[18] This less frequent dosing schedule, if successful, would represent a significant improvement in convenience and treatment burden for patients with a chronic disease. The program, which began enrolling patients in the fourth quarter of 2023, is expected to yield primary results in 2026.[18]

Core Phase III Efficacy and Safety Trials

The OCEANA program is composed of several pivotal trials, each designed to answer specific clinical questions:

• COAST 1 (NCT06130566) & COAST 2 (NCT06181435): These are twin, pivotal, randomized, double-blind, placebo-controlled trials designed to evaluate Amlitelimab as a monotherapy.[16] They are enrolling adolescents (aged 12 and older) and adults with moderate-to-severe AD whose disease is inadequately controlled with topical prescription therapies.[19] The primary endpoints, including the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 and a 75% improvement in the Eczema Area and Severity Index (EASI-75), will be assessed at Week 24.[18]
• SHORE (NCT06224348): This Phase III trial is designed to assess the efficacy and safety of Amlitelimab when used in combination with standard-of-care topical corticosteroids (TCS), with or without topical calcineurin inhibitors (TCIs).[16] This design reflects a common real-world clinical practice and is essential for understanding the drug's performance as part of a comprehensive treatment regimen. Its patient population and primary endpoint timing (Week 24) are similar to the COAST trials.[18]
• AQUA (NCT06241118): This trial is strategically designed to evaluate Amlitelimab in a more treatment-experienced and difficult-to-treat population.[16] It will enroll adolescents and adults who have had an inadequate response or are intolerant to prior advanced therapies, including other biologics or oral Janus kinase (JAK) inhibitors.[19] A positive outcome in the AQUA trial would be particularly impactful, as it would position Amlitelimab as an effective option for patients who have failed other systemic treatments. This study has a 36-week primary endpoint evaluation period.[18]

The inclusion of the AQUA trial directly within the pivotal program, rather than as a post-marketing study, reflects a high level of confidence in Amlitelimab's potent and broad mechanism of action. It is an aggressive strategy aimed at establishing the drug's value in the highest unmet need patient segment from the moment of potential launch, seeking to prove its ability to overcome the limitations of therapies that target more downstream inflammatory pathways.

Long-Term Extension and Maintenance Studies

To complement the core efficacy trials, the OCEANA program includes several long-term studies to assess durability, maintenance of response, and long-term safety:

• ESTUARY (NCT06407934): This is a 52-week, randomized, double-blind extension study for participants who successfully complete the COAST or SHORE trials.[18] Its main objective is to formally evaluate the maintenance of clinical response in initial responders, comparing continued treatment at different dosing intervals against a planned treatment withdrawal (placebo) arm.[25]
• RIVER-AD (NCT05492578, LTS17367): This is a long-term, open-label extension study that will enroll participants from various feeder studies, including AQUA and ESTUARY.[16] The primary purpose of RIVER-AD is to gather extensive long-term safety, tolerability, and efficacy data over a planned duration of up to 120-160 weeks.[27] This study will be crucial for characterizing the chronic safety profile of Amlitelimab.
• ATLANTIS (NCT05769777): This is another Phase II, open-label, long-term safety and efficacy study enrolling participants aged 12 and older for a treatment period of up to 160 weeks (approximately three years), further contributing to the comprehensive long-term safety database.[16]

Table 2: Summary of Key Clinical Trials in the OCEANA Program for Atopic Dermatitis

Trial Name (NCT ID)	Phase	Primary Objective	Patient Population	Design	Primary Endpoint(s) & Timepoint
COAST 1/2 (NCT06130566, NCT06181435)	III	Evaluate efficacy and safety of Amlitelimab monotherapy	Ages ≥12 with moderate-to-severe AD, inadequate response to topicals	Randomized, Double-Blind, Placebo-Controlled	IGA 0/1 & EASI-75 at Week 24
SHORE (NCT06224348)	III	Evaluate efficacy and safety with background topical therapies	Ages ≥12 with moderate-to-severe AD	Randomized, Double-Blind, Placebo-Controlled, with TCS/TCI	IGA 0/1 & EASI-75 at Week 24
AQUA (NCT06241118)	III	Evaluate efficacy and safety in treatment-experienced patients	Ages ≥12 with moderate-to-severe AD, inadequate response to prior biologics or JAK inhibitors	Randomized, Double-Blind, Placebo-Controlled, with TCS/TCI	IGA 0/1 & EASI-75 at Week 36
ESTUARY (NCT06407934)	III	Evaluate maintenance of response and withdrawal	Responders from COAST 1/2 and SHORE trials	Randomized, Double-Blind, Placebo-Controlled Extension	Maintenance of response at Week 52
RIVER-AD (NCT05492578)	II	Evaluate long-term safety, tolerability, and efficacy	Participants from previous Amlitelimab trials	Open-Label Extension	Long-term safety and efficacy
ATLANTIS (NCT05769777)	II	Evaluate long-term safety, tolerability, and efficacy	Ages ≥12 with moderate-to-severe AD	Open-Label, Single-Arm	Long-term safety and efficacy

Clinical Efficacy in Atopic Dermatitis: Analysis of Phase II and III Programs

The clinical efficacy of Amlitelimab in atopic dermatitis has been systematically evaluated through a phased approach, with each study building upon the last to establish a robust evidence base. The results from the Phase II program have been particularly compelling, providing the foundation for the ambitious Phase III OCEANA program.

Phase IIa (NCT03754309) Proof-of-Concept

The initial proof-of-concept for Amlitelimab in AD was established in a Phase IIa, randomized, double-blind, placebo-controlled study involving 89 adult patients with moderate-to-severe disease.[1] Participants received intravenous (IV) Amlitelimab at either a low dose (200 mg loading) or a high dose (500 mg loading), or placebo, followed by maintenance doses every four weeks for 16 weeks.[7]

The study successfully demonstrated clinically meaningful improvements in the signs and symptoms of AD.[7] The co-primary efficacy endpoint was the mean percentage change in the Eczema Area and Severity Index (EASI) score from baseline to Week 16. The low-dose Amlitelimab group achieved a mean reduction of -80.12%, which was statistically significant compared to the -49.37% reduction seen in the placebo group (

p=0.009).[7] The high-dose group showed a strong trend towards improvement with a -69.97% reduction (

p=0.072 vs. placebo).[7] The onset of action was rapid, with a numerical separation from placebo observed as early as Week 2.[32] These initial results provided the first clinical validation of targeting OX40L in AD and supported progression to a larger dose-ranging study with a subcutaneous formulation.

Phase IIb (STREAM-AD, NCT05131477) Dose-Ranging and Durability

The Phase IIb STREAM-AD study was a larger, two-part trial that enrolled 390 adults and was designed to determine the optimal subcutaneous dose and, critically, to explore the durability of the treatment effect.[17]

Part 1 (0-24 Weeks): Dose-Ranging Efficacy

In the first 24-week treatment period, participants were randomized to one of four subcutaneous Amlitelimab doses (62.5 mg, 125 mg, 250 mg, and 250 mg with a 500 mg loading dose) or placebo, administered every four weeks.[33] The study met its primary endpoint, with all four Amlitelimab arms demonstrating statistically significant improvements in the percent change in EASI score from baseline at Week 16 compared to placebo (

p<0.001).[3]

The 250 mg Q4W with 500 mg LD arm emerged as the highest-performing dose, showing a -61.5% reduction in EASI at Week 16, which continued to improve to -64.4% by Week 24. This was substantially greater than the approximate -28% to -29% reduction observed in the placebo group at the same timepoints (p<0.0001).[35] This dose was subsequently selected for the Phase III program.[20]

Significant improvements were also consistently observed across key secondary endpoints.[3] For instance, by Week 24, 45.5% of patients in the highest dose group achieved an IGA score of 0 (clear) or 1 (almost clear), demonstrating a marked improvement in overall disease severity.[35] Furthermore, the trial showed a meaningful reduction in itch, a highly burdensome symptom of AD. In one analysis, 74% of patients continuing on Amlitelimab maintained a clinically significant improvement of at least 4 points on the Peak Pruritus-Numerical Rating Scale (PP-NRS).[17]

Part 2 (24-52 Weeks): Maintenance and Unprecedented Off-Drug Durability

The second part of the STREAM-AD study yielded the program's most transformative findings. Clinical responders from Part 1 were re-randomized to either continue their assigned Amlitelimab dose or be withdrawn from treatment (switched to placebo) for an additional 28 weeks.[20] This design allowed for a direct assessment of the durability of Amlitelimab's effect after its discontinuation.

The results were remarkable, demonstrating a sustained clinical response in a majority of patients who stopped active treatment. Analysis of the withdrawal arm showed that 63% of patients maintained a significant reduction in itch (PP-NRS improvement ≥4) for the full 28 weeks after their last active dose.[17] When assessing a composite endpoint of maintaining either EASI-75 and/or an IGA score of 0/1, between 59% and 66% of patients in the withdrawal groups maintained their response at Week 52.[36]

This durable clinical benefit was corroborated by objective biomarker evidence. Key AD-related inflammatory biomarkers, such as IL-22, Thymus and Activation-Regulated Chemokine (TARC), and eosinophil counts, which were significantly reduced during the initial treatment phase, remained suppressed throughout the 28-week off-treatment period.[20] This sustained normalization of objective inflammatory markers, even as serum concentrations of Amlitelimab became negligible, provides strong evidence that the drug's effect outlasts its physical presence in the body.[20] This phenomenon points toward a fundamental resetting of the immune system's pathological state rather than simple, transient suppression of inflammatory signals. It is this potential for true disease modification that underpins the investigation of a quarterly dosing regimen and distinguishes Amlitelimab from other biologics that typically require continuous administration to maintain efficacy.

Table 3: Key Efficacy Results from the Phase IIb STREAM-AD Trial

Endpoint	Timepoint	Amlitelimab 250mg + LD	Placebo	Key Finding
Part 1: Treatment Phase
Mean % Change in EASI from Baseline	Week 16	-61.5%	-29.4%	Met primary endpoint (p<0.0001) 35
Mean % Change in EASI from Baseline	Week 24	-64.4%	-27.6%	Continued improvement over time 35
% Achieving IGA 0/1	Week 24	45.5%	N/A	Clinically meaningful improvement in skin clearance 35
Part 2: Withdrawal Phase (Responders)
% Maintaining IGA 0/1 and/or EASI-75	Week 52	59% (Withdrawn)	N/A	High rate of sustained response 28 weeks off-drug 36
% Maintaining PP-NRS ≥4 Improvement	Week 52	63% (Withdrawn)	N/A	Durable and meaningful itch relief off-drug 17

Exploratory Indications: Clinical Evidence in Asthma and Other Immune-Mediated Disorders

Leveraging its broad, upstream mechanism of action, Sanofi is exploring the therapeutic potential of Amlitelimab beyond atopic dermatitis. The most advanced of these exploratory programs is in asthma, with several other immune-mediated diseases also under investigation in Phase II trials.

Asthma (TIDE-Asthma, NCT05421598)

The TIDE-Asthma study was a Phase II, randomized, dose-ranging trial that evaluated Amlitelimab as an add-on therapy for 437 adults with moderate-to-severe asthma who were inadequately controlled on standard-of-care medications.[14] The results of this trial were nuanced and provided critical insights into the drug's activity and the importance of patient stratification.

The study did not meet its primary endpoint of a statistically significant reduction in the annualized rate of severe asthma exacerbations at Week 48 for the highest dose tested. However, the medium dose did show a nominally significant and clinically meaningful reduction in exacerbations.[14] Despite the miss on the primary endpoint in the overall population, Sanofi highlighted what it termed "compelling efficacy" in a specific, pre-defined patient subgroup.[13]

This key finding emerged from the analysis of patients with a distinct "heterogeneous inflammatory asthma" phenotype, characterized by both high baseline blood eosinophils (≥300 cells/mL) and elevated neutrophils. In this specific population, Amlitelimab demonstrated a substantial treatment effect, reducing asthma exacerbations by over 70% at Week 60, along with clinically meaningful improvements in lung function (pre-BD FEV1​) and asthma control.[13]

These results underscore a critical lesson in modern immunology drug development: the era of a "one-size-fits-all" approach is waning. While the broad anti-inflammatory mechanism of Amlitelimab is highly effective in the general AD population, its efficacy in asthma appears to be concentrated in patients with a specific, measurable immunologic profile. This suggests that the inflammatory pathways dependent on OX40L signaling are the primary drivers of disease in this subgroup, but less so in the broader asthma population. Consequently, Sanofi is moving forward with plans for a Phase III program in asthma, which will almost certainly be designed with a precision-medicine approach, focusing on enrolling patients with the biomarker signature that predicts a strong response.[13]

Other Potential Indications

The strong scientific rationale for inhibiting the OX40-OX40L axis in T-cell-driven diseases has prompted the investigation of Amlitelimab across a spectrum of other immune-mediated and inflammatory disorders.[3] The drug is currently in active Phase II clinical development for the following conditions [5]:

• Hidradenitis Suppurativa: A chronic, inflammatory skin disease characterized by painful nodules and abscesses.
• Alopecia Areata: An autoimmune disorder that causes hair loss.
• Celiac Disease: An autoimmune condition triggered by gluten ingestion that leads to intestinal damage.
• Systemic Scleroderma (Systemic Sclerosis): A rare autoimmune disease characterized by fibrosis of the skin and internal organs.

Initial development programs for graft-versus-host disease and psoriasis appear to have been deprioritized or discontinued, as they are no longer reported in the development pipeline.[5] Success in these ongoing Phase II studies could significantly expand the potential therapeutic footprint of Amlitelimab, transforming it from a dermatology-focused asset into a broad-spectrum immunomodulatory therapy.

Safety and Tolerability Profile

A favorable safety and tolerability profile is paramount for any therapy intended for chronic use, particularly in non-life-threatening conditions like atopic dermatitis. Across its clinical development program to date, Amlitelimab has consistently demonstrated an encouraging safety profile, which is a key component of its potential best-in-class positioning.

Summary of Safety Findings Across Trials

Data aggregated from the Phase IIa and Phase IIb (STREAM-AD) trials in atopic dermatitis, as well as the Phase II TIDE-Asthma trial, have consistently characterized Amlitelimab as "well-tolerated" with an "unremarkable safety profile".[7] Importantly, no new or unexpected safety signals have emerged with longer-term exposure in studies extending up to 68 weeks.[20] This consistent safety record across different patient populations and study durations provides a strong foundation of confidence as the drug progresses through its large-scale Phase III program.

Treatment-Emergent Adverse Events (TEAEs)

In the largest controlled dataset from the 24-week treatment period of the STREAM-AD trial, the overall incidence of treatment-emergent adverse events was similar between patients receiving any dose of Amlitelimab and those receiving placebo. The combined Amlitelimab arms reported a TEAE rate of 67.4%, compared to 60.3% in the placebo arm.[34] The vast majority of these events were mild or moderate in severity.[39]

The most frequently reported TEAEs that occurred at a slightly higher incidence in the Amlitelimab groups compared to placebo were [34]:

• Nasopharyngitis (11.0% vs. 9.0%)
• COVID-19 (7.7% vs. 6.4%)
• Headache (6.1% vs. 2.6%)

In the TIDE-Asthma study, bronchitis and acute sinusitis were also noted as being more common than placebo.[39] Notably, the incidence of "worsening of atopic dermatitis" was substantially higher in the placebo group (38.5%) compared to the Amlitelimab group (17.1%), reflecting the therapeutic effect of the drug.[35] Serious adverse events (SAEs) were rare and occurred at similar rates between treatment and placebo groups. One SAE (infected atheroma) was deemed related to the study drug in the Phase IIa trial, which resolved without complication.[32]

Adverse Events of Special Interest (AESI)

A significant aspect of Amlitelimab's safety profile is the notable absence of certain adverse events that have been associated with other systemic therapies for atopic dermatitis. This clean profile on specific AESIs is a key potential differentiator.

• Conjunctivitis: Unlike IL-13 pathway inhibitors such as dupilumab, where conjunctivitis is a well-documented adverse event, clinical trials with Amlitelimab have reported no imbalance in the rates of conjunctivitis compared to placebo.[34]
• Systemic Inflammatory Symptoms: No adverse events such as fever, chills, or oral ulcers, which can sometimes be associated with immunomodulatory agents, were observed across the dose arms in the STREAM-AD study.[34]
• Hypersensitivity: No hypersensitivity events were reported in the Phase IIa trial.[7]

This favorable AESI profile may be linked to Amlitelimab's specific, non-depleting mechanism of action that preserves the function of regulatory T-cells.

Long-Term Safety Evaluation

While the data to date are robust, establishing the safety of Amlitelimab over many years of potential use is a critical next step. This is the primary objective of the ongoing open-label extension studies, including RIVER-AD (NCT05492578) and ATLANTIS (NCT05769777).[28] These trials will follow patients for up to three years or more, generating a comprehensive database that will be essential for regulatory submissions and for providing clinicians and patients with confidence regarding the long-term safety of the therapy.[27]

Table 4: Summary of Common Treatment-Emergent Adverse Events (TEAEs) from STREAM-AD (Part 1, 24 Weeks)

Adverse Event	Amlitelimab (All Doses, N=311) %	Placebo (N=78) %
Overall TEAEs	67.4%	60.3%
Nasopharyngitis	11.0%	9.0%
COVID-19	7.7%	6.4%
Headache	6.1%	2.6%
Worsening of Atopic Dermatitis	17.1%	38.5%
Data sourced from Sanofi press release 34

Strategic Analysis: Competitive Landscape and Future Outlook

Amlitelimab is entering a dynamic and increasingly crowded therapeutic landscape for atopic dermatitis. Its ultimate success will depend not only on its clinical profile but also on its ability to differentiate itself from a range of existing and emerging competitors. The analysis of its strategic position reveals a clear value proposition built on a unique mechanism, potential for best-in-class durability and convenience, and a favorable safety profile.

Positioning Against Current Standard of Care

The treatment paradigm for moderate-to-severe AD has evolved significantly. For patients who fail to achieve adequate control with foundational therapies like emollients and topical corticosteroids, the next line of treatment typically involves advanced systemic agents.[43] The current landscape is defined by two major classes:

• Biologics: This class is dominated by dupilumab (Dupixent), an IL-4/IL-13 inhibitor that has become the gold standard for systemic therapy in AD due to its strong efficacy and well-established safety profile.[12] Other IL-13 inhibitors like lebrikizumab and tralokinumab are also entering the market.[45] Amlitelimab will need to demonstrate compelling advantages to compete, with its potential for less frequent dosing (quarterly vs. bi-weekly for Dupixent) and efficacy in a broader patient population being key potential differentiators.[45]
• Oral Janus Kinase (JAK) Inhibitors: Agents like abrocitinib (Cibinqo) and upadacitinib (Rinvoq) offer the convenience of oral administration and rapid onset of action.[48] However, their use is tempered by U.S. FDA-mandated boxed warnings regarding risks of serious infections, malignancy, major adverse cardiovascular events (MACE), and thrombosis.[50] Amlitelimab's clean safety profile to date, lacking these class-specific warnings, presents a major competitive advantage, particularly for patients and physicians prioritizing long-term safety.

Direct Competitor Analysis: Amlitelimab (anti-OX40L) vs. Rocatinlimab (anti-OX40)

The most direct and mechanistically related competitor to Amlitelimab is rocatinlimab, an anti-OX40 monoclonal antibody being developed by Amgen and Kyowa Kirin.[10] Both drugs target the same co-stimulatory axis, but their distinct molecular targets lead to fundamentally different biological effects.

• Mechanistic Distinction and Its Implications: As previously discussed, rocatinlimab binds to the OX40 receptor on activated T-cells, leading to their selective depletion.[2] In contrast, Amlitelimab binds to the OX40L on APCs, preventing T-cell activation in a non-depleting manner while sparing Tregs.[2] This mechanistic divergence could have significant clinical consequences. While both approaches are effective at reducing inflammation, Amlitelimab's Treg-sparing, immunomodulatory approach may offer a superior long-term safety profile by avoiding T-cell depletion and may be the underlying reason for its unique durable off-drug effect.
• Comparative Efficacy and Safety: Direct head-to-head trials are not available, making cross-trial comparisons speculative. However, initial data readouts provide some context. In its Phase III ROCKET-HORIZON trial, rocatinlimab demonstrated a placebo-adjusted EASI-75 response rate of 19.1% at Week 24.[54] While Amlitelimab's Phase III data is pending, its Phase IIb results suggest a numerically potent efficacy profile. On the safety front, rocatinlimab has been associated with adverse events such as pyrexia (fever), chills, and aphthous ulcers, which have not been prominent features in Amlitelimab's clinical program to date, further suggesting a potential differentiation in tolerability.[55]

Key Differentiators and Value Proposition

Amlitelimab's potential to become a best-in-class therapy is built on a convergence of four key differentiating attributes:

1. Durable, Off-Drug Efficacy: The most compelling feature is the sustained clinical and biomarker response observed for months after treatment cessation in the STREAM-AD trial. This suggests a disease-modifying potential that could lead to long-term remission or control with intermittent therapy, a significant paradigm shift in managing a chronic disease.[17]
2. Extended Dosing Interval: The observed durability directly supports the viability of a quarterly (Q12W) maintenance dosing schedule being tested in Phase III. This would offer a profound improvement in convenience and treatment burden compared to the bi-weekly or monthly injections required for current biologics, likely leading to enhanced patient adherence and preference.[18]
3. Broad-Spectrum Efficacy: By targeting an upstream checkpoint that influences multiple T-cell lineages, Amlitelimab has the potential to effectively treat patients with varied inflammatory profiles, including those with significant non-Type 2 inflammation who may respond sub-optimally to more targeted therapies like IL-13 inhibitors.[1]
4. Favorable Safety Profile: The non-depleting, Treg-sparing mechanism appears to translate into a well-tolerated safety profile, free from the boxed warnings of JAK inhibitors and potentially avoiding some of the specific adverse events (e.g., conjunctivitis) seen with other biologics.[17]

Regulatory Status

Amlitelimab is currently an investigational new drug and has not yet been granted marketing authorization by any global regulatory agency, including the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).[3] It is classified as a New Molecular Entity (NME) but does not hold an Orphan Drug Status designation, which is consistent with its development for a prevalent condition like atopic dermatitis.[5] The available documentation does not indicate that it has received special regulatory designations such as FDA Fast Track or EMA PRIME (PRIority MEdicines).[60] The successful completion of the ongoing Phase III OCEANA program will be the prerequisite for submitting applications for regulatory approval.

Table 5: Comparative Profile of Amlitelimab vs. Key Competitors in Atopic Dermatitis

Attribute	Amlitelimab	Dupixent (dupilumab)	Rocatinlimab	Oral JAK Inhibitors (e.g., abrocitinib)
Target/MoA	Anti-OX40L (non-depleting, Treg-sparing immunomodulation)	Anti-IL-4Rα (blocks IL-4/IL-13 signaling)	Anti-OX40 (depletes activated T-cells)	JAK1/STAT pathway inhibition
Dosing Frequency	Potentially Q12W (every 12 weeks)	Q2W (every 2 weeks)	Q2W or Q4W	Once Daily (Oral)
Key Efficacy Metric	High EASI-75 response in Phase IIb	Established high efficacy (benchmark)	EASI-75 response demonstrated in Phase III	Rapid and high efficacy
Durability/Off-Drug Effect	Demonstrated strong, durable off-drug response	Relapse upon discontinuation	Durability suggested in Phase IIb	Relapse upon discontinuation
Key Safety/Tolerability Concerns	Well-tolerated; no major signals identified	Conjunctivitis, injection site reactions	Pyrexia, chills, aphthous ulcers	FDA Boxed Warning (infections, malignancy, MACE, thrombosis)

Conclusion and Forward Projections

Amlitelimab (SAR445229) has emerged from clinical development as a highly differentiated and promising therapeutic candidate for atopic dermatitis and other immune-mediated diseases. Its unique, upstream mechanism of action—selectively targeting the OX40 ligand to modulate T-cell activity while preserving essential regulatory T-cells—represents a sophisticated and potentially superior approach to restoring immune balance.

The clinical evidence to date, particularly from the Phase IIb STREAM-AD study, is exceptionally strong. Amlitelimab has demonstrated not only robust efficacy in reducing the signs and symptoms of moderate-to-severe atopic dermatitis but has also revealed an unprecedented potential for durable, off-drug disease control. This finding, supported by objective biomarker data, suggests a true disease-modifying effect that could fundamentally alter long-term treatment strategies. The translation of this durability into a potential quarterly maintenance dosing regimen would offer a transformative improvement in patient convenience and adherence, establishing a new benchmark in the field. Combined with a consistently favorable safety and tolerability profile that appears to avoid the key liabilities of other systemic therapies, Amlitelimab possesses a compelling and multifaceted value proposition.

The future of the Amlitelimab program hinges on the outcomes of the comprehensive Phase III OCEANA trials. These studies are well-designed to confirm the efficacy, safety, and unique durability profile in a large, diverse patient population, including those who have failed previous advanced therapies. Positive readouts from this program would solidify Amlitelimab's position as a potential first- and best-in-class therapy. Key catalysts will be the topline data releases from the COAST, SHORE, and AQUA trials, anticipated in 2026.

In conclusion, Amlitelimab is not merely another entrant into the immunology market; it is a potential paradigm-shifting agent. If its Phase III program confirms the promise shown in Phase II, Amlitelimab is poised to capture a significant share of the atopic dermatitis market and could become a foundational therapy for a host of other chronic inflammatory conditions, offering patients the prospect of profound and lasting disease control with an infrequent and well-tolerated treatment regimen.

Works cited

1. Safety of Amlitelimab in a Phase 2a Clinical Trial of Patients With Moderate-to-Severe Atopic Dermatitis - Sanofi Congress, accessed August 13, 2025, https://congress.sanofimedical.com/s3fs-public/2023-02/GE141-21%20AAD23%20Amlitelimab%20Ph2a%20Safety%20ePoster%20VP10_UPLOAD.pdf?VersionId=gv0PMAKxscdMy22XkMLMUoRq4mDKcHpX
2. OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis - Encyclopedia.pub, accessed August 13, 2025, https://encyclopedia.pub/entry/41305
3. Press Release: Positive topline Phase 2b data in atopic dermatitis support amlitelimab as a potential first and best-in-class novel investigational anti-OX40-ligand monoclonal antibody - Sanofi, accessed August 13, 2025, https://www.sanofi.com/en/media-room/press-releases/2023/2023-06-27-05-30-00-2694938
4. What is Amlitelimab used for? - Patsnap Synapse, accessed August 13, 2025, https://synapse.patsnap.com/article/what-is-amlitelimab-used-for
5. Amlitelimab - Kymab/Sanofi - AdisInsight - Springer, accessed August 13, 2025, https://adisinsight.springer.com/drugs/800050071
6. Amlitelimab by Sanofi for Atopic Dermatitis (Atopic Eczema): Likelihood of Approval, accessed August 13, 2025, https://www.pharmaceutical-technology.com/data-insights/amlitelimab-sanofi-atopic-dermatitis-atopic-eczema-likelihood-of-approval/
7. Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial - PubMed, accessed August 13, 2025, https://pubmed.ncbi.nlm.nih.gov/37463508/
8. UNII - YZ6BH6TN8P, accessed August 13, 2025, https://precision.fda.gov/uniisearch/srs/unii/YZ6BH6TN8P
9. Amlitelimab - Drug Targets, Indications, Patents - Patsnap Synapse, accessed August 13, 2025, https://synapse.patsnap.com/drug/6c6ba9a7ce66499a8f763a78a752605b
10. Sanofi chalks up another win for its immune system research | BioPharma Dive, accessed August 13, 2025, https://www.biopharmadive.com/news/sanofi-amlitelimab-eczema-study-results-immunology-kymab/654027/
11. Sanofi's $1.1B eczema drug hits goal, spurring talk of phase 3 - Fierce Biotech, accessed August 13, 2025, https://www.fiercebiotech.com/biotech/sanofis-11b-eczema-drug-hits-midphase-goal-spurring-talk-phase-3-and-new-indications
12. Sanofi to increase competition in atopic dermatitis market after Dupixent success, accessed August 13, 2025, https://www.clinicaltrialsarena.com/analyst-comment/sanofi-atopic-dermatitis-market-dupixent/
13. Sanofi's $1.4B Kymab Bet Falters as Asthma Drug Stumbles in Phase II - BioSpace, accessed August 13, 2025, https://www.biospace.com/drug-development/sanofis-1-4b-kymab-bet-falters-as-asthma-drug-stumbles-in-phase-ii
14. Sanofi's high hopes for $1.1B Kymab anti-inflammatory drug dented after phase 2 asthma failure - Fierce Biotech, accessed August 13, 2025, https://www.fiercebiotech.com/biotech/sanofis-high-hopes-11b-kymab-anti-inflammatory-drug-dented-after-phase-2-asthma-failure
15. Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial - Oxford Academic, accessed August 13, 2025, https://academic.oup.com/bjd/article/189/5/531/7226167
16. OCEANA Clinical Program Investigating amlitelimab in Atopic Dermatitis - Sanofi, accessed August 13, 2025, https://www.sanofi.com/en/our-science/clinical-trials-and-results/oceana-clinical-program-investigating-amlitelimab-in-atopic-dermatitis
17. Amlitelimab Demonstrates Durable Response in Atopic Dermatitis - Dermatology Times, accessed August 13, 2025, https://www.dermatologytimes.com/view/amlitelimab-demonstrates-durable-response-in-atopic-dermatitis
18. Amlitelimab (an anti-OX40 Ligand Antibody) vs Placebo in Patients With Moderate-to-severe Atopic Dermatitis: Study Design of Phase 3 OCEANA Clinical Trials COAST 1/2, SHORE, AQUA, and ESTUARY - Congresso Nazionale ADOI, accessed August 13, 2025, https://congressonazionaleadoi.it/documento/a-12-week-safety-assessment-of-rilzabrutinib-in-patients-with-chronic-spontaneous-urticaria-from-the-rilecsu-phase-2-dose-ranging-study/
19. Abstract N°: 3372 Amlitelimab (an anti-OX40 Ligand antibody) vs placebo in patients with moderate-to-severe atopic dermatitis: - Amazon S3, accessed August 13, 2025, https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.eadv/abstracts_congress_2024/44846.pdf
20. Press Release: New Phase 2b results for amlitelimab support potential for best-in-class maintenance of response in atopic dermatitis - Sanofi, accessed August 13, 2025, https://www.sanofi.com/en/media-room/press-releases/2024/2024-03-11-06-00-00-2843456
21. Study Details | A Study to Evaluate the Efficacy and Safety of ..., accessed August 13, 2025, https://clinicaltrials.gov/study/NCT06130566?intr=Amlitelimab&rank=6
22. Study Details | A Study to Evaluate the Efficacy and Safety of ..., accessed August 13, 2025, https://clinicaltrials.gov/study/NCT06224348
23. Clinical Trials in the European Union - EMA, accessed August 13, 2025, https://euclinicaltrials.eu/ctis-public/view/2023-508099-12-00
24. A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab on Background Topical Corticosteroids Therapy in Participants Aged 12 Years and Older With Moderate-to-severe AD Who Have Had an Inadequate Response to Prior Biologic Therapy or an Oral JAK Inhibitor (AQUA) - ClinicalTrials.Veeva, accessed August 13, 2025, https://ctv.veeva.com/study/a-study-to-evaluate-the-efficacy-and-safety-of-subcutaneous-amlitelimab-on-background-topical-cortic
25. A Study to Evaluate the Treatment Response and ... - ClinicalTrials.gov, accessed August 13, 2025, https://clinicaltrials.gov/study/NCT06407934
26. Amlitelimab for Eczema · Recruiting Participants for Phase Phase 3 Clinical Trial 2025, accessed August 13, 2025, https://www.withpower.com/trial/phase-3-dermatitis-atopic-4-2024-5673c
27. RIVER - AD - NHS Health Research Authority, accessed August 13, 2025, https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/river-ad/
28. Open Label, Long-term Study Evaluating Safety and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis | Clinical Research Trial Listing - CenterWatch, accessed August 13, 2025, https://www.centerwatch.com/clinical-trials/listings/NCT05769777/open-label-long-term-study-evaluating-safety-and-efficacy-of-subcutaneous-amlitelimab-in-participants-aged-12-years-and-older-with-moderate-to-severe-atopic-dermatitis
29. Study Details | Open Label, Long-term Study Evaluating Safety and ..., accessed August 13, 2025, https://clinicaltrials.gov/study/NCT05769777
30. Open Label, Long-term Study Evaluating Safety and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis | ClinicalTrials.gov, accessed August 13, 2025, https://clinicaltrials.gov/study/NCT05769777?cond=Atopic%20dermatitis&intr=Amlitelimab&rank=1
31. Safety and efficacy of amlitelimab, a fully human, non-depleting, non-cytotoxic anti-OX40Ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomised placebo-controlled trial - ResearchGate, accessed August 13, 2025, https://www.researchgate.net/publication/372445768_Safety_and_efficacy_of_amlitelimab_a_fully_human_non-depleting_non-cytotoxic_anti-OX40Ligand_monoclonal_antibody_in_atopic_dermatitis_results_of_a_phase_IIa_randomised_placebo-controlled_trial
32. Press Release: New, late-breaking data at EADV highlights emerging clinical profile of amlitelimab (formerly KY1005) in adults with inadequately controlled moderate-to-severe atopic dermatitis - Sanofi, accessed August 13, 2025, https://www.sanofi.com/en/media-room/press-releases/2021/2021-09-30-12-30-00-2306183
33. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis - PubMed, accessed August 13, 2025, https://pubmed.ncbi.nlm.nih.gov/39522654/
34. Late-breaking amlitelimab Phase 2b data presented at EADV show potential best-in-class profile in atopic dermatitis - SEC.gov, accessed August 13, 2025, https://www.sec.gov/Archives/edgar/data/1121404/000119312523259842/d568063dex991.htm
35. Press Release: Late-breaking amlitelimab Phase 2b data presented at EADV show potential best-in-class profile in atopic dermatitis - Sanofi, accessed August 13, 2025, https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-13-14-00-00-2760021
36. 661 - Efficacy and safety of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis (AD): a phase 2b trial (STREAM-AD) | British Journal of Dermatology | Oxford Academic, accessed August 13, 2025, https://academic.oup.com/bjd/article-abstract/191/Supplement_2/ljae266.039/7728690
37. 345 Treatment with amlitelimab—a novel non-depleting, non-cytotoxic anti-OX40Ligand monoclonal antibody—reduces IL-22 serum levels in a phase 2a randomized, placebo-controlled trial in patients with moderate-to-severe atopic dermatitis | Quanterix, accessed August 13, 2025, https://www.quanterix.com/posters/345-treatment-with-amlitelimab-a-novel-non-depleting-non-cytotoxic-anti-ox40ligand-monoclonal-antibody-reduces-il-22-serum-levels-in-a-phase-2a-randomized-placebo-controlled-trial-in/
38. Sanofi's amlitelimab shows best-in-class response in atopic ..., accessed August 13, 2025, https://www.clinicaltrialsarena.com/news/sanofis-amlitelimab-shows-best-in-class-response-in-atopic-dermatitis/
39. Press Release: Sanofi's respiratory pipeline advances with new data ..., accessed August 13, 2025, https://www.sanofi.com/en/media-room/press-releases/2025/2025-04-15-05-00-00-3061368
40. Amlitelimab: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed August 13, 2025, https://go.drugbank.com/drugs/DB18835
41. Phase 2b Data Shows Amlitelimab's 68-Week Safety for Atopic Dermatitis - HCPLive, accessed August 13, 2025, https://www.hcplive.com/view/phase-2b-data-shows-amlitelimab-s-68-week-safety-for-atopic-dermatitis
42. Study Details | Long-Term Safety and Efficacy Evaluation of Amlitelimab in Participants of Previous Amlitelimab Moderate to Severe Atopic Dermatitis Clinical Trials | ClinicalTrials.gov, accessed August 13, 2025, https://clinicaltrials.gov/study/NCT05492578?cond=Atopic%20dermatitis&intr=Amlitelimab&rank=8
43. Atopic Dermatitis: Update on Skin-Directed Management: Clinical Report - AAP Publications, accessed August 13, 2025, https://publications.aap.org/pediatrics/article/155/6/e2025071812/201952/Atopic-Dermatitis-Update-on-Skin-Directed
44. Atopic Dermatitis: Diagnosis and Treatment - AAFP, accessed August 13, 2025, https://www.aafp.org/pubs/afp/issues/2020/0515/p590.html
45. AAD Daily: Atopic dermatitis agents move towards less-frequent dosing, oral JAK inhibitor shows rapid action in PN…and more - FirstWord Pharma, accessed August 13, 2025, https://firstwordpharma.com/story/5835512
46. Lebrikizumab Medication, accessed August 13, 2025, https://en.wikipedia.org/wiki/Lebrikizumab
47. Adbry® (tralokinumab-ldrm) for moderate-to-severe Eczema, accessed August 13, 2025, https://www.adbry.com/
48. en.wikipedia.org, accessed August 13, 2025, https://en.wikipedia.org/wiki/Abrocitinib
49. FAQ – Rinvoq (Upadacitinib) | National Eczema Association, accessed August 13, 2025, https://nationaleczema.org/faq-upadacitinib/
50. Why Do JAK Inhibitors for Eczema Have a Black Box Warning? - Healthline, accessed August 13, 2025, https://www.healthline.com/health/eczema/black-box-jak-inhibitors-eczema
51. Oral JAK inhibitors unlikely to be totally shut out in eczema by black box warning, accessed August 13, 2025, https://www.clinicaltrialsarena.com/features/jak-inhibitors-atopic-dermatitis/
52. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions, accessed August 13, 2025, https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
53. JAK Inhibitors for Atopic Dermatitis - WebMD, accessed August 13, 2025, https://www.webmd.com/skin-problems-and-treatments/eczema/jak-inhibitors-atopic-dermatitis
54. Amgen secures Phase 3 successes in atopic dermatitis and myasthenia gravis, accessed August 13, 2025, https://synapse.patsnap.com/article/amgen-secures-phase-3-successes-in-atopic-dermatitis-and-myasthenia-gravis
55. Is OX40 Inhibition the Next Game Changer for Atopic Dermatitis? - Dermatology Times, accessed August 13, 2025, https://www.dermatologytimes.com/view/is-ox40-inhibition-the-next-game-changer-for-atopic-dermatitis-
56. Kyowa Kirin Announces Top-line Data from Rocatinlimab Phase 3 ROCKET HORIZON Trial for Adults with Moderate to Severe Atopic Dermatitis, accessed August 13, 2025, https://www.kyowakirin.com/media_center/news_releases/2024/pdf/e20240925_01.pdf
57. Amgen, Kyowa Kirin's Rocatinlimab Picks Up Steam With Late-Stage Atopic Dermatitis Win, accessed August 13, 2025, https://www.biospace.com/drug-development/amgens-rocatinlimab-picks-up-steam-with-late-stage-atopic-dermatitis-win
58. AMGEN AND KYOWA KIRIN PROVIDE TOP-LINE RESULTS FROM ROCATINLIMAB PHASE 3 IGNITE STUDY IN ADULTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS, accessed August 13, 2025, https://www.amgen.com/newsroom/press-releases/2025/03/amgen-and-kyowa-kirin-provide-top-line-results-from-rocatinlimab-phase-3-ignite-study-in-adults-with-moderate-to-severe-atopic-dermatitis
59. Press Release: Positive topline Phase 2b data in atopic dermatitis support amlitelimab as a potential first and best-in-class novel investigational anti-OX40-ligand monoclonal antibody - GlobeNewswire, accessed August 13, 2025, https://www.globenewswire.com/news-release/2023/06/27/2694938/0/en/Press-Release-Positive-topline-Phase-2b-data-in-atopic-dermatitis-support-amlitelimab-as-a-potential-first-and-best-in-class-novel-investigational-anti-OX40-ligand-monoclonal-antib.html
60. FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma, accessed August 13, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-linvoseltamab-gcpt-relapsed-or-refractory-multiple-myeloma
61. Clinical Trials in the European Union - EMA, accessed August 13, 2025, https://euclinicaltrials.eu/ctis-public/view/2023-506557-38-00