amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

The keyhole limpet hemocyanin (KLH) challenge model to establish early clinical proof-of-mechanism of investigational drugs for auto-immune diseases. (EULAR 2025) - "Next steps include further exploration of the translation of the KLH model from HV to rheumatoid arthritis (RA) patients by investigating the KLH response in treatment naïve RA patients that are starting methotrexate (MTX) therapy in responders compared to non-responders to MTX therapy. Early phase proof-of-mechanism studies help to elucidate the pharmacological mechanism of action of novel drugs in vivo , and establish the dose-response relationship. Our studies demonstrate that KLH drives an antigen-specific immune response in man in vivo , displaying Th1, Th2 and Th17 characteristics. Our KLH model allows evaluation of systemic antigen-specific responses but also in peripheral tissue."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IFNG • IL13 • TNFSF4

Amlitelimab Reduces Th2-, Th1-, and Th17/22-Related Gene Expression and Protein Levels in Adults With Moderate-to-Severe Atopic Dermatitis: Results From an Exploratory Analysis of the Phase 2b STREAM-AD Study (EAACI 2025) - No abstract available

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Immunology

Biologics targeting OX40 and OX40L for treatment of atopic dermatitis have distinct inhibitory binding mechanisms (SID 2025) - "Our results provide initial prediction and analysis of the epitopes of OX40 and OX40L targeted biologics emerging for AD treatment. Rocatinlimab and amlitelimab appear to directly inhibit OX40-OX40L interactions via steric occlusion, with amlitelimab also possibly inhibiting OX40L trimer formation, whereas telazorlimab more specifically disrupts a critical intermolecular interaction."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Amlitelimab reduces atopic dermatitis-related gene expression elevated in lesional skin: An analysis of the phase 2b STREAM-AD study (SID 2025) - P2 | "Amlitelimab led to downregulation of Th1 (eg, CXCL9 and CXCL10; P<0.05), Th2 (eg, CCL13 and CCL18; P<0.05), and Th17/22 (eg, S100A8 and S100A9; P<0.05) pathway-associated genes in lesional skin at Wk16 compared with baseline, and a greater % recovery toward nonlesional gene expression levels than placebo. The observed normalization of AD-related genes in lesional skin after 16wks of amlitelimab treatment supports the clinical improvements seen in AD lesions in STREAM-AD."

IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL18 • CXCL10 • CXCL9 • S100A8 • S100A9

OX40/OX40L as a Therapeutic Target in Atopic Dermatitis: A Scoping Review. (PubMed, Biologics) - "Moreover, early basic and clinical research has shown encouraging results regarding the efficacy and safety of therapies targeting the OX40-OX40L axis in moderate-to-severe AD. Therefore, herein we aim to summarize the current evidence regarding the efficacy and safety of inhibiting the OX40/OX40L signaling axis in patients with moderate-to-severe AD."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Safety and Efficacy of Anti-OX40 Therapies in Atopic Dermatitis: A Systematic Review and Meta-Analysis. (PubMed, Dermatitis) - "We aimed to systematically evaluate the efficacy and safety of anti-OX40 therapies (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. In conclusion, anti-OX40 therapies demonstrate clinically meaningful efficacy and an acceptable safety profile for moderate-to-severe AD, offering a potential alternative for patients with inadequate responses to current treatments. Further research is warranted to confirm these results and to refine optimal dosing strategies."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Investigating Efficacy of Atopic Dermatitis Systemic Therapeutics After Discontinuation Part I: Biologics. (PubMed, J Clin Aesthet Dermatol) - "Five clinical trial programs met our inclusion criteria, each investigating a different biologic: dupilumab, tralokinumab, lebrikizumab, amlitelimab, and rocatinlimab. The variability in eligibility criteria, treatment durations, and withdrawal periods across trials presents a major challenge in assessing biologics for AD, complicating the comparison of their sustained responses in the absence of head-to-head studies. This heterogeneity, combined with factors such as disease duration and prior use of systemic medications before trial enrollment, hampers the identification of key pathways in AD pathogenesis and impedes efforts to better understand and characterize the disease."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Interim results of RIVER-AD: 28-week open-label safety and efficacy of amlitelimab in patients with atopic dermatitis not initially achieving clinical response at Week 24 of the STREAM-AD phase 2b trial (AAD 2025) - P2/3 | "This interim analysis evaluated safety, change in EASI, EASI-75, EASI-90, and IGA 0/1 response following 28-weeks of subcutaneous amlitelimab 250mg every-4-weeks (Q4W) in RIVER-AD in participants not achieving clinical response at Week 24 of STREAM-AD with amlitelimab or placebo. Interim RIVER-AD results demonstrated clinical improvements after 28 weeks of subcutaneous 250mg Q4W amlitelimab treatment in participants with moderate-to-severe AD not achieving clinical response at Week 24 of STREAM-AD, with a safety profile similar to that observed in STREAM-AD."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Impact of amlitelimab (an anti-OX40 Ligand antibody) on maintenance of itch response in atopic dermatitis: results from the 52-week STREAM-AD Phase 2b study (AAD 2025) - P2 | "In the STREAM-AD Phase 2b trial, many patients treated with amlitelimab who demonstrated skin improvements also experienced improvements in itch at Week 24. A majority of the clinical responders who saw itch reduction at Week 24 maintained this reduction on- or off-amlitelimab for the 28-week withdrawal period, demonstrating durable and sustained itch responses following amlitelimab treatment."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

Amlitelimab Reduces Th2-, Th1-, and Th17/22-Related Cytokines and Chemokines in Adults With Moderate-to-Severe Atopic Dermatitis): Results From an Exploratory Analysis of the Phase 2b STREAM-AD Study (AAD 2025) - P2 | "In Part 1, adults with moderate-to-severe AD were randomized to receive subcutaneous amlitelimab (250mg with 500-mg loading dose, 250mg, 125mg, 62.5mg) or placebo every 4 weeks. Amlitelimab significantly reduced proteins associated with AD inflammation in adults with moderate-to-severe AD, further supporting that OX40L blockade is a relevant target for treating AD-related inflammation."

Clinical • IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • CCL2 • CCL20 • CCL22 • CXCL10 • CXCL9 • IL13 • IL17A • IL17C • IL6 • TNFSF4

Targeting OX40-OX40L pathway: A new era in atopic dermatitis management by T cell rebalancing. (PubMed, J Allergy Clin Immunol) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TNFSF4

Amlitelimab (anti-OX40 ligand antibody) significantly reduces serum IgE and LDH levels and epidermal hyperplasia in adults with moderate to severe atopic dermatitis (JDP 2024) - No abstract available

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Narrative Review of the OX40-OX40L Pathway as a Potential Therapeutic Target in Atopic Dermatitis: Focus on Rocatinlimab and Amlitelimab. (PubMed, Dermatol Ther (Heidelb)) - "Although initial results are promising, further research is needed to evaluate the long-term effects, durability of response, and safety of these treatments. These findings support the therapeutic potential of targeting the OX40-OX40L pathway in AD, providing new options for patients with moderate-to-severe disease, with ongoing trials necessary to confirm their sustained benefits."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Design of CONQUEST, a novel, randomized, placebo-controlled, Phase 2b platform clinical trial to investigate new treatments for patients with early active systemic sclerosis with interstitial lung disease. (PubMed, J Scleroderma Relat Disord) - P2 | "The first molecules to be studied, amlitelimab and nerandomilast, both have a strong scientific rationale to modify underlying disease processes in systemic sclerosis. Platform Clinical Study for Conquering Scleroderma (CONQUEST); NCT06195072; https://www.clinicaltrials.gov/study/NCT06195072."

Journal • P2b data • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. (PubMed, J Allergy Clin Immunol) - P2 | "Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks."

Clinical • IO biomarker • Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Sanofi gets CDSCO Panel Nod To Study Amlitelimab (Medical Dialogues) - "The drug major Sanofi has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organization (CDSCO) to conduct a phase III clinical study of Amlitelimab....However, this approval is subject to the requirement that the firm submit a separate detailed protocol and procedure to ensure standardized monitoring across all the study sites, specifically a detailed document informing investigators about screening for cutaneous/extracutaneous lymphoma steps of diagnosis and reporting to CDSCO."

New P3 trial • Cutaneous T-cell Lymphoma • Oncology

STRATEGIES FOR INCREASING RACIAL AND ETHNIC DIVERSITY IN AN ASTHMA CLINICAL TRIAL: TIDE STUDY (ACAAI 2024) - P2 | " TIDE (NCT05421598) is a randomized, double-blind, placebo-controlled study, evaluating the efficacy and safety of subcutaneously administered amlitelimab (an investigational anti-OX40L monoclonal antibody) in adults with moderate-to-severe asthma... The implemented strategies achieved D&I goals, ensuring fair representation of different patient populations in the TIDE study. Consequently, the study data will be relevant across patient groups, limiting bias towards any single population. Figure 1."

Clinical • Late-breaking abstract • Asthma • Immunology • Inflammation • Respiratory Diseases • TNFSF4

Prediction of the efficacy of extended dosing of amlitelimab (an anti-OX40 Ligand antibody) in patients with moderate-to-severe atopic dermatitis using a modeling approach (EADV 2024) - "The PopPK/PD-EASI model simulations support the Q12W extended dose regimen for Phase 3 studies, demonstrating 250mg Q12W +LD predicts similar exposures and efficacy in the range of Q4W dosing regimens evaluated in the STREAM-AD Phase 2b trial."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Impact of amlitelimab (an anti-OX40 Ligand antibody) on atopic dermatitis of the head and neck: post hoc results from the STREAM-AD phase 2b study of moderate-to-severe atopic dermatitis (EADV 2024) - P2 | "In Part 1, adult participants with moderate-to-severe AD were randomised 1:1:1:1:1 to subcutaneous amlitelimab every 4 weeks (250 mg with 500 mg loading dose (250 mg +LD), n=77; 250 mg, n=78; 125 mg, n=77; 62.5 mg, n=79) or placebo every 4 weeks (n=79) . Amlitelimab improved EASI head and neck subscores vs placebo at Week 24, and was effective across all signs (erythema, oedema/papulation, excoriation, and lichenification) of head and neck AD. Amlitelimab may be an effective future treatment option for patients with moderate-to-severe AD with hard-to-treat lesions on the head and neck."

P2b data • Retrospective data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TNFSF4

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 (EADV 2024) - "Results should provide further evidence demonstrating the efficacy and safety of** amlitelimab in treating moderate-to-severe AD using two different dosing regimens, including an extended dosing regimen, in patients with various treatment histories."

Clinical • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

In vitro evidence demonstrating the nondepleting mechanism of action of amlitelimab, an OX40 Ligand monoclonal antibody (EADV 2024) - "Activated T cells and Tregs remained intact upon amlitelimab treatment, whereas OX40-expressing activated CD4 T cells and Tregs were found to be depleted via ADCC upon treatment with anti-OX40 antibodies. These antibodies also led to a reduction in the percentage of live Tregs. Furthermore, no ADCC activity was observed against hOX40L-transfected HEK cells with amlitelimab, suggesting a nondepleting mechanism of action for amlitelimab."

IO biomarker • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CD4 • FOXP3 • IL2RA • IL7R • TNFSF4

Amlitelimab (an anti-OX40 Ligand antibody) normalises the atopic dermatitis gene signature in the skin of patients with moderate-to-severe atopic dermatitis (EADV 2024) - P2 | "In Part 1, adults with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab (250 mg with 500 mg loading dose (LD; n=77), 250 mg (n=78), 125 mg (n=77), or 62.5 mg (n=79)) , or placebo (n=79) every 4 weeks over 24 weeks. Following 16 weeks of treatment with amlitelimab, a normalisation in the AD gene signature was observed in lesional skin compared to baseline, supporting the clinical improvements seen in AD lesions ."

Clinical • Gene Signature • IO biomarker • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

68-week safety results of amlitelimab (an anti-OX40 Ligand antibody) in patients with moderate-to-severe atopic dermatitis from STREAM-AD Phase 2b dose-ranging and withdrawal study (EADV 2024) - P2 | "Part 1 involved a 24-week treatment period (last dose at Week 20) with 388 participants treated with subcutaneous amlitelimab or placebo every 4 weeks (Q4W; 250mg with 500mg loading dose (250mg +LD), n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=78; placebo, n=78) . In the STREAM-AD Phase 2b trial, amlitelimab was well tolerated and demonstrated an acceptable safety profile in the Part 2 (responder) population up to 68 weeks."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TNFSF4

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis. (PubMed, J Clin Med) - "There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions."

Journal • P3 data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Sanofi (SNY.US)’s Class 1 new drug amlitelimab has been approved for clinical use in China to treat severe alopecia areata [Google translation] (Sina Corp) - "On July 29, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that Sanofi's (SNY.US) Class 1 new drug amlitelimab injection was approved for clinical use for the treatment of severe alopecia areata...The approval of the clinical trial for severe alopecia areata means that Sanofi will soon conduct clinical research on alopecia areata patients in China."

New trial • Alopecia • Dermatology • Immunology