The investigational biologic lunsekimig improved lung function and reduced flare-ups in clinical respiratory studies.
RT’s Three Key Takeaways:
- Dual-Target Mechanism: The investigational biologic lunsekimig is designed to simultaneously block two distinct inflammatory drivers, thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13), to combat airway inflammation and tissue damage.
- Asthma Trial Outcomes: In the phase 2b AIRCULES study, lunsekimig significantly lowered asthma exacerbation rates and improved pre-bronchodilator forced expiratory volume in one second (FEV1) in adults with moderate-to-severe disease.
- Sinus Disease Efficacy: The phase 2a DUET trial demonstrated that the therapy met primary and secondary endpoints in chronic rhinosinusitis with nasal polyps, significantly reducing polyp burden and sinus congestion compared to placebo.
The investigational biologic lunsekimig met primary and key secondary endpoints in two phase 2 clinical trials evaluating chronic respiratory conditions, including moderate-to-severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), according to Sanofi.
Lunsekimig is a novel bispecific antibody fragment construct designed to simultaneously inhibit TSLP and IL-13, two key cytokines that drive persistent airway inflammation and structural tissue damage. Across both trials, the company reported that the drug was well tolerated with an acceptable safety profile compared to placebo.
“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 and development at Sanofi. “Importantly, these findings underscore lunsekimig’s potential to address multiple critical aspects of respiratory disease management through its unique mechanism.”
Lung Function Improvements in Moderate-to-Severe Asthma
In the randomized, double-blind, placebo-controlled phase 2b AIRCULES trial, investigators evaluated subcutaneous lunsekimig as an add-on therapy to standard of care in adult patients with moderate-to-severe asthma across a broad range of fractional exhaled nitric oxide (FeNO) and blood eosinophil levels, according to Sanofi.
The study achieved its primary endpoint by demonstrating a statistically significant and clinically meaningful decrease in the annualized rate of asthma exacerbations over 48 weeks. Lunsekimig also met its key secondary endpoint, producing significant improvements in pulmonary function as measured by pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1) at week 48. The clinical trial included study sites across the US, Canada, the UK, China, and several other countries.
Efficacy in Chronic Rhinosinusitis with Nasal Polyps
The phase 2a DUET proof-of-concept study assessed subcutaneous lunsekimig in adult patients with CRSwNP over 24 weeks. The trial met its primary endpoint, showing a statistically significant change in endoscopic nasal polyp scores from baseline compared to placebo at week 24, according to Sanofi.
In addition, the therapy met key secondary endpoints, demonstrating meaningful improvements in patient-reported nasal congestion and obstruction scores, as well as Lund-Mackay Computed Tomography (LMK-CT) sinus imaging scores at week 24.
Safety and Clinical Pipeline Progress
Sanofi reported that rates of serious adverse events and treatment-emergent adverse events leading to discontinuation were similar between lunsekimig and placebo groups in both respiratory studies. In the AIRCULES asthma trial, the most common treatment-emergent adverse events occurring in at least 5% of patients included nasopharyngitis, upper respiratory tract infection, headache, and dose scheduling errors. In the DUET trial, frequent adverse events included injection site reactions or erythema, viral upper respiratory tract infections, nasopharyngitis, epistaxis, ear pain, and increased creatine phosphokinase.
In a separate exploratory phase 2b trial in moderate-to-severe atopic dermatitis, dubbed VELVET, lunsekimig missed its primary endpoint of percent change in Eczema Area and Severity Index (EASI) score at week 24, though secondary endpoints measuring skin clearance showed improvement, according to the company.
Full data sets from the AIRCULES, DUET, and VELVET trials will be presented at upcoming medical congresses. Lunsekimig remains under clinical investigation in the phase 2 AIRLYMPUS study for high-risk asthma, as well as the PERSEPHONE and THESEUS phase 3 clinical programs, and its safety and efficacy have not yet been evaluated by the Food and Drug Administration (FDA) or other regulatory authorities.
