Lunsekimig Meets End Points in Asthma and CRSwNP, Misses in Atopic Dermatitis

Sanofi's lunsekimig, a novel bispecific agent designed to simultaneously block thymic stromal lymphopoietin (TSLP) and interleukin (IL)-13, met its primary and key secondary endpoints in 2 phase 2 respiratory studies — but failed to meet its primary end point in a concurrent exploratory study in moderate-to-severe atopic dermatitis, the company announced April 7.¹

“These data are promising and support our belief that the dual-targeting mechanism of lunsekimig may offer a novel treatment option for patients living with respiratory diseases, including asthma,” said Houman Ashrafian, Executive Vice President, Head of Research & Development at Sanofi.1 “Importantly, these findings underscore lunsekimig’s potential to address multiple critical aspects of respiratory disease management through its unique mechanism.”

Lunsekimig is a pentavalent Nanobody® VHH construct consisting of five linked antibody fragments. Its mechanism targets both an upstream initiator of type 2 airway inflammation (TSLP) and a downstream effector cytokine (IL-13), with preclinical data suggesting that simultaneous dual blockade may yield additive or synergistic effects beyond what either target alone can achieve.¹ A 2025 phase 1b proof-of-mechanism study in 36 adults with mild-to-moderate asthma supported this rationale, finding that a single subcutaneous dose produced rapid, significant reductions in fractional exhaled nitric oxide (FENO) — a marker of airway inflammation — alongside decreases in blood eosinophil counts and other type 2 biomarkers.²

In the phase 2b AIRCULES study (NCT06102005), lunsekimig was evaluated as add-on to standard of care in adults with moderate-to-severe asthma across the range of FENO and eosinophil values — a biomarker-unselected design intended to assess whether efficacy is maintained regardless of type 2 inflammatory status. The primary endpoint was the annualized rate of asthma exacerbation events over 48 weeks, with pre-bronchodilator forced expiratory volume in 1 second (FEV1) at week 48 as the key secondary endpoint. Lunsekimig met both, demonstrating a statistically significant and clinically meaningful reduction in exacerbations and improvement in lung function compared with placebo.¹ Full numeric data have not yet been disclosed and are expected to be presented at an upcoming medical congress.

In the phase 2a DUET study (NCT06454240), lunsekimig met its primary endpoint of change in nasal polyp score from baseline at week 24, assessed via bilateral endoscopy, in adults with chronic rhinosinusitis with nasal polyps (CRSwNP) — a condition in which the majority of patients carry comorbid asthma, particularly those with more severe disease. Key secondary endpoints — patient-reported nasal congestion/obstruction score and Lund-Mackay CT score, both at week 24 — were also met compared to placebo.¹ Detailed results from DUET are similarly forthcoming.

The separate exploratory phase 2b VELVET study (NCT06790121) evaluated lunsekimig in adults with moderate-to-severe atopic dermatitis and did not meet its primary endpoint of percent change from baseline in Eczema Area and Severity Index (EASI) score at week 24. Improvements were observed in certain key secondary endpoints, including EASI-75 response rates and vIGA-AD 0/1 scores, but the primary miss limits interpretation of those findings. Sanofi characterized VELVET as exploratory and has described respiratory indications as the primary development focus for lunsekimig.¹

Across all 3 studies, lunsekimig was generally well tolerated. In AIRCULES, treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients who received lunsekimig included nasopharyngitis, upper respiratory tract infection, headache, and dose scheduling errors. In DUET, TEAEs at that threshold included injection site reaction or erythema, viral upper respiratory tract infection, nasopharyngitis, epistaxis, ear pain, and increased creatine phosphokinase. Rates of serious AEs and TEAEs leading to discontinuation were similar between lunsekimig and placebo groups in both studies. The safety profile in VELVET was consistent with the other studies.¹

Lunsekimig's development program continues to expand: it is currently being evaluated in the AIRLYMPUS phase 2 study in high-risk asthma (NCT06676319) and in 2 phase 3 studies — PERSEPHONE and THESEUS (NCT07190209 and NCT07190222, respectively) — in chronic obstructive pulmonary disease. Its safety and efficacy have not yet been evaluated by any regulatory authority.¹

References

1. Sanofi. Sanofi's lunsekimig met primary and key secondary endpoints in phase 2 respiratory studies in asthma and CRSwNP. Press release. April 7, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-04-07-05-00-00-3268809

2. Zielen S, Ulrik CS, Bobolea I, et al. A proof-of-mechanism trial in asthma with lunsekimig, a bispecific NANOBODY molecule. Eur Respir J. 2025;65(4):2401461. doi:10.1183/13993003.2401461