Lunsekimig Demonstrates Reductions in Asthma Exacerbations in Phase 2 Trials

In an advancement for the treatment of chronic respiratory conditions, Sanofi announced that its novel biologic lunsekimig successfully met primary and key secondary end points in 2 major phase 2 clinical trials. The AIRCULES (NCT06102005) phase 2b study demonstrated a statistically significant and clinically meaningful reduction in asthma exacerbations and improved lung function in adults with moderate-to-severe asthma, notably achieving these results regardless of a patient's baseline biomarker status.¹

Simultaneously, the DUET (NCT06454240) phase 2a proof-of-concept study in chronic rhinosinusitis with nasal polyps (CRSwNP) reached its primary end point by significantly improving nasal polyp scores compared to placebo at week 24.

“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,” Houman Ashrafian, executive vice president and head of research and development at Sanofi, said in a news release.

For pharmacists, the clinical relevance of lunsekimig lies in its innovative structure as a bispecific Nanobody VHH molecule. Unlike traditional monoclonal antibodies (mAbs), Nanobody molecules are approximately 10 times smaller and are derived from heavy-chain-only antibody fragments found in camelids.^1-3

Lunsekimig is a pentavalent construct consisting of 5 linked antibody fragments including 2 targeting thymic stromal lymphopoietin (TSLP), 2 targeting interleukin-13 (IL-13), and 1 designed to bind to human serum albumin to extend the drug’s half-life. By simultaneously blocking TSLP, an upstream initiator of inflammation, and IL-13, a downstream cytokine that causes tissue damage and mucus secretion, the drug aims to provide additive or synergistic benefits that may surpass the efficacy of current single-target biologics.^1,2

Pharmacokinetic data from earlier first-in-human studies support a favorable profile for clinical use, showing a dose-proportional increase in exposure and linear elimination. In healthy volunteers, lunsekimig exhibited a terminal half-life of approximately 10 to 11 days across both intravenous and subcutaneous routes, with an absolute bioavailability of 54% following a single subcutaneous dose. This linear pharmacokinetic profile remained consistent in participants with mild-to-moderate asthma, where the drug was observed to reach maximum plasma concentration about 5 days after administration. Pharmacists should also note that because Nanobody molecules lack the Fc portion found in conventional mAbs, lunsekimig does not trigger Fc-mediated effector functions such as complement activation or phagocytic clearance, potentially reducing certain off-target risks.^2,3

The safety and tolerability of lunsekimig have remained acceptable across the developmental spectrum, from phase 1 trials through the most recent phase 2 respiratory studies. In the AIRCULES asthma trial, the most common treatment-emergent adverse events were nasopharyngitis, upper respiratory tract infections, and headache. In the DUET CRSwNP study, injection site reactions and erythema were more frequent, though generally mild and self-limiting.^1,2

Although an exploratory phase 2b trial in atopic dermatitis, known as VELVET (NCT06790121), failed to meet its primary endpoint regarding percent change in eczema area severity index (EASI) score, researchers observed improvements in secondary measures of skin clearance, and the drug’s safety profile remained consistent with the respiratory studies.¹

From a pharmacodynamic perspective, lunsekimig has shown a rapid and robust impact on type 2 inflammatory biomarkers. Earlier proof-of-mechanism studies in patients with asthma demonstrated that a single dose could significantly reduce the fraction of exhaled nitric oxide, a key marker of airway inflammation, as early as day 8. Furthermore, the drug has been shown to reduce blood eosinophil counts, IL-5, and IgE levels, as well as improve small airway dysfunction in patients with impaired lung function at baseline.³

As lunsekimig moves into phase 3 studies, it represents a promising new tool for pharmacists and clinicians seeking to manage patients who remain uncontrolled on standard-of-care inhaled corticosteroids.¹

“Importantly, these findings underscore lunsekimig’s potential to address multiple critical aspects of respiratory disease management through its unique mechanism,” Ashrafian said in the news release.

READ MORE: Asthma Resource Center

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REFERENCES

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

2. Deiteren A, Bontinck L, Conickx G, et al. A first-in-human, single and multiple dose study of lunsekimig, a novel anti-TSLP/anti-IL-13 NANOBODY compound, in healthy volunteers. Clin Transl Sci. 2024;17(6):e13864. doi:10.1111/cts.13864

3. Deiteren A, Krupka E, Bontinck L, et al. A proof-of-mechanism trial in asthma with lunsekimig, a bispecific NANOBODY molecule. Eur Respir J. 2025;65(4):2401461. Published 2025 Apr 24. doi:10.1183/13993003.01461-2024