Sanofi reported Phase 2 results for lunsekimig showing significant improvements in asthma and CRSwNP, while the atopic dermatitis study missed its primary endpoint despite secondary benefits and a favorable safety profile.
Written By: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Sanofi reported that multiple Phase 2 studies evaluating lunsekimig, an investigational bispecific Nanobody targeting thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13), met primary and key secondary endpoints in chronic respiratory diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The therapy was generally well tolerated across studies.
Dual-Target Mechanism Designed to Address Airway Inflammation
Lunsekimig is a pentavalent bispecific Nanobody composed of five linked antibody fragments designed to simultaneously block TSLP, an upstream initiator of inflammation, and IL-13, a downstream cytokine associated with tissue damage in respiratory diseases. This dual-target approach aims to address multiple drivers of airway inflammation and improve disease control in conditions such as asthma.
Houman Ashrafian, Executive Vice President and Head of Research and Development at Sanofi, stated that the data support the dual-targeting mechanism of lunsekimig and highlight its potential as a treatment option for respiratory diseases, including asthma, by addressing multiple aspects of disease management.
AIRCULES Phase 2b Study in Moderate-to-Severe Asthma
In the Phase 2b AIRCULES trial (NCT06102005), lunsekimig achieved its primary and key secondary endpoints. The study demonstrated a statistically significant reduction in asthma exacerbations and improvements in lung function measured by pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1).
The randomized, double-blind, placebo-controlled study evaluated subcutaneous lunsekimig added to standard of care in adults with moderate-to-severe asthma. The primary endpoint assessed annualized exacerbation rate over 48 weeks, while the key secondary endpoint evaluated lung function improvement at Week 48.
DUET Phase 2a Study in CRSwNP
The Phase 2a DUET proof-of-concept study (NCT06454240) met its primary endpoint, demonstrating improvement in nasal polyp score compared with placebo at Week 24. The trial also met key secondary endpoints, including improvements in patient-reported nasal congestion/obstruction scores and Lund-Mackay CT scores.
This randomized, double-blind, placebo-controlled study evaluated subcutaneous lunsekimig in adults with chronic rhinosinusitis with nasal polyps over 24 weeks.
VELVET Phase 2b Study in Atopic Dermatitis
The exploratory Phase 2b VELVET study (NCT06790121) in moderate-to-severe atopic dermatitis did not meet its primary endpoint of percent change from baseline in eczema area and severity index (EASI) score at Week 24. However, improvements were observed in key secondary endpoints, including EASI-75 and validated investigator global assessment for atopic dermatitis (vIGA-AD 0/1), indicating improved skin clearance in some patients.
Safety Profile
Across studies, lunsekimig was generally well tolerated. In the AIRCULES trial, the most common treatment-emergent adverse events (≥5%) included nasopharyngitis, upper respiratory tract infection, headache, and dose scheduling errors.
In the DUET study, common adverse events included injection-site reactions, viral upper respiratory tract infection, nasopharyngitis, epistaxis, ear pain, and increased creatine phosphokinase. Rates of serious adverse events and treatment discontinuations were similar between lunsekimig and placebo groups. The safety profile in VELVET was consistent with other studies.
Ongoing Clinical Development
Lunsekimig continues in clinical development, including the Phase 2 AIRLYMPUS study in high-risk asthma (NCT06676319) and two Phase 3 trials, PERSEPHONE (NCT07190209) and THESEUS (NCT07190222). The therapy has not yet been evaluated by regulatory authorities.
Disease Background
Asthma affects an estimated 262 million people globally, and more than half of patients remain inadequately controlled despite available therapies. Chronic rhinosinusitis with nasal polyps is a persistent inflammatory disease characterized by nasal polyps and symptoms such as congestion, facial pressure, and reduced sense of smell, often occurring with comorbid asthma.
References
Press Release: Sanofi’s lunsekimig met primary and key secondary endpoints in phase 2 respiratory studies in asthma and CRSwNP, 07 April 2026, Press Release: Sanofi’s lunsekimig met primary and key secondary endpoints in phase 2 respiratory studies in asthma and CRSwNP
Dose Ranging Study of Lunsekimig Compared with Placebo-control in Adult Participants with Moderate-to-severe Asthma (AIRCULES), ClinicalTrials.gov ID NCT06102005, https://clinicaltrials.gov/study/NCT06102005
A Proof-of-concept Study of Lunsekimig Compared with Placebo in Adults with Chronic Rhinosinusitis with Nasal Polyps, ClinicalTrials.gov ID NCT06454240, https://clinicaltrials.gov/study/NCT06454240
A Study to Investigate the Efficacy and Safety of Subcutaneous Lunsekimig (SAR443765) Compared with Placebo in Adult Participants with Moderate-to-severe Atopic Dermatitis, ClinicalTrials.gov ID NCT06790121, https://clinicaltrials.gov/study/NCT06790121
About the Writer
Dr. Anuja Badgujar, BDS, is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.