amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

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

CONQUEST: Platform Clinical Study for Conquering Scleroderma (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Scleroderma Research Foundation, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Development and characterization of STAR-0310: a novel OX40 antagonistic monoclonal antibody (EAACI 2024) - "STAR-0310 is being compared to telazorlimab, rocatinlimab, and amlitelimab in detailed preclinical pharmacology studies including in vitro potency of T cell proliferation inhibition, cytotoxicity effects on activated T cells and regulatory T cells. Conclusion STAR-0310, an anti-OX40 antibody, demonstrates the potential for increased half-life, high-potency T cell inhibition, and reduced toxicities with minimized effector (ADCC) functions. These promising preclinical findings support the potential use of STAR-0310 in moderate-to-severe AD and other immunologic diseases."

Atopic Dermatitis • Dermatitis • Immunology • TNFSF4

Amlitelimab (an OX40 ligand antibody) significantly reduces serum IgE and LDH, and epidermal hyperplasia in adults with moderate-to-severe atopic dermatitis (EAACI 2024) - P2 | "In Part 1, adults with moderate-to-severe AD were randomized 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD; n=77], 250 mg [n=78], 125 mg [n=77], 62.5 mg [n=79]), or placebo (n=79) every 4 weeks over 24 weeks. At Week 16, amlitelimab significantly reduced epidermal thickness (p<0.01) and cytokeratin 16 staining in the epidermis (p<0.001), while epidermal thickness and cytokeratin 16 staining were not significantly reduced in the placebo arm (p=0.71 and p=0.71, respectively). Conclusion Amlitelimab significantly reduced serum total IgE and LDH levels as well as epidermal hyperplasia in adults with moderate-to-severe AD, further supporting that OX40L blockade is a relevant target for the treatment of AD-related inflammation."

Clinical • IO biomarker • Atopic Dermatitis • Dermatitis • Immunology • KRT16 • TNFSF4

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) (EAACI 2024) - P2 | "In Part 1, adult participants were randomized 1:1:1:1:1 to subcutaneous amlitelimab Q4W (250mg with 500mg loading dose [+ LD], n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=79) or placebo Q4W (n=79). Conclusion Clinically meaningful efficacy with amlitelimab was demonstrated over 52 wks, with an acceptable safety profile. Clinical responses were maintained in most patients 28 wks after treatment discontinuation."

Clinical • IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Immunology • TNFSF4

Submit Preliminary Analysis Of Primary Data Of Subjects Above 18 Years In India: CDSCO Panel Tells Sanofi On Amlitelimab Study (Medical Dialogues) - "After considering the phase III clinical study protocol of the monoclonal antibody Amlitelimab in the treatment of moderate-to-severe Atopic Dermatitis, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug major Sanofi to submit the preliminary analysis of primary data of subjects above 18 years..."

Clinical protocol • Atopic Dermatitis • Immunology

Amlitelimab improves extent and severity of disease in adults with moderate-to-severe atopic dermatitis (AD): 24-week results from a Phase 2b trial (STREAM-AD) (EADV-Sp 2024) - P2 | "Amlitelimab improved metrics of disease extent and severity in adults with moderate-to-severe AD in the first 24 weeks of this Phase 2b trial, with greatest improvement seen in the 250 mg plus LD arm."

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

Improvements on patient-reported outcome (PRO) measures with 24 weeks of amlitelimab treatment in adults with moderate-to-severe atopic dermatitis: results from a Phase 2b trial (STREAM-AD) (EADV-Sp 2024) - P2 | "Amlitelimab improved metrics of disease severity, disease control, and QoL, with the greatest improvement seen in the 250 mg with LD arm."

Clinical • P2b data • Patient reported outcomes • Atopic Dermatitis • Dermatitis • Dermatology • Immunology