Sanofi’s Lunsekimig Meets Phase 2 Endpoints in Asthma and CRSwNP, Showing Promise as a Dual-Targeting Respiratory Therapy

Phase 2 clinical data from Sanofi highlight the potential of lunsekimig as an innovative therapy for respiratory diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The investigational drug met primary and key secondary endpoints in two studies, reinforcing its promise as a dual-target biologic designed to address complex inflammatory pathways.¹

Lunsekimig is a bispecific Nanobody® therapy engineered to simultaneously block thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13), both of which play critical roles in driving inflammation and tissue damage in respiratory conditions. By targeting these two pathways, the therapy aims to provide broader and more effective disease control compared with single-target treatments.

Lunsekimig is comprised of five linked antibody fragments, with a mechanism of action that targets the upstream initiator of type 2 airway inflammation (TSLP) and the downstream effector cytokine (IL-13). Preclinical data has indicated that blocking both TSLP and IL-13 may produce additional or synergistic effects beyond what blocking either pathway individually may be able to accomplish.

In a Phase 1b proof-of-mechanism trial, 36 adults with mild-to-moderate asthma were administered lunsekimig, with results showing that one subcutaneous dose achieved a quick and significant decrease in fractional exhaled nitric oxide and lowered blood eosinophil counts, as well as other type 2 biomarkers.²

“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 and head of Research & Development at Sanofi, in a press release.

Strong Results in Asthma: AIRCULES Trial

The Phase IIb trial (2026) showed that lunsekimig significantly reduced

annualized asthma exacerbation rates compared to placebo at week 48 in patients with moderate-to-severe asthma. The trial met its primary and key secondary endpoints, including improved lung function (pre-BD FEV1). Importantly, benefits were observed regardless of biomarker status, suggesting broader applicability across patient subgroups.

Positive Outcomes in CRSwNP: DUET Study

The Phase 2a DUET study (NCT06454240) included adults with moderate-to-severe CRSwNP, many of whom have persistent symptoms despite standard care, such as steroids. Lunsekimig met its primary endpoint by significantly reducing nasal polyp scores compared with placebo at week 24.

Key secondary endpoints also showed improvement, including reductions in nasal congestion and better imaging outcomes based on Lund-Mackay CT scores. These findings demonstrate the therapy’s potential to address both structural and symptomatic aspects of CRSwNP.

Mixed Results in Atopic Dermatitis: VELVET Study

In the Phase 2b VELVET study (NCT06790121), lunsekimig did not meet its primary endpoint of improving EASI scores in moderate-to-severe atopic dermatitis. However, secondary outcomes showed promise, with more patients achieving EASI-75 and vIGA-AD 0/1 responses, indicating clearer skin.

These results suggest potential biologic activity despite the primary endpoint miss, according to the trial investigators. Overall, findings highlight a complex efficacy profile and support further research to better understand lunsekimig’s role in treating dermatologic conditions.

Safety and Future Outlook

The results from AIRCULES and DUET underscore a growing emphasis on therapies that simultaneously target multiple inflammatory pathways. Lunsekimig’s dual mechanism of action, inhibiting both TSLP and IL-13, may offer a differentiated and potentially more comprehensive approach to treating complex respiratory diseases such as asthma and CRSwNP.

The therapy is currently being evaluated in additional clinical studies, including the Phase 2 AIRLYMPUS trial in high-risk asthma, as well as the Phase 3 PERSEPHONE and THESEUS trials. If these studies confirm its efficacy and safety, lunsekimig could represent a meaningful advancement in the management of asthma and other chronic inflammatory respiratory conditions, potentially improving outcomes and expanding treatment options for patients.

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. Deiteren A, Krupka E, Bontinck L, Imberdis K, Conickx G, Bas S, Patel N, Staudinger HW, Suratt BT. A proof-of-mechanism trial in asthma with lunsekimig, a bispecific NANOBODY molecule. Eur Respir J. 2025 Apr 24;65(4):2401461. doi: 10.1183/13993003.01461-2024. PMID: 39884759; PMCID: PMC12018761.