• The objective of the VESTIGE clinical investigation is to evaluate dupilumab's propitious influence on lung function as well as structural airway alterations using functional respiratory imaging (FRI), a revolutionary technology that uses high-resolution CT (HRCT) images to construct 3D visualizations and quantify airway structure and function. 
• The VESTIGE trial represents the largest study to date that uses functional respiratory imaging (FRI) to assess the effects of dupilumab on lung function and airway volume changes in moderate-to-severe asthma.

As per Asthma – Market Insight, Epidemiology, and Market Forecast – 2034, it is estimated that approximately 56 million individuals were diagnosed in the 7MM (including the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan) in 2023. However, the trajectory of this widespread condition is poised to evolve in the coming years. By 2034, our analysts predict a notable surge in asthma cases within these regions, reflecting the urgent need for continued research, improved treatments, and enhanced public health initiatives to address this growing global health concern.

Dupilumab, a proprietary intravenous formulation for airway oscillometry, ventilation/perfusion, and mucus plugging in individuals with moderate-to-severe asthma. Dupilumab blocks the shared receptor component for interleukins-4/13, drivers of type 2 inflammation, and improves lung function in patients with moderate-to-severe asthma, potentially by reducing airway inflammation. Sanofi put forward findings regarding dupilumab at the American Thoracic Society (ATS) 2024 International Conference on May 20, 2024. The presentations featured outcomes from the Vestige trial (NCT04400318), a Phase IV imaging investigations. 

Key findings from the Vestige study reported include changes from baseline to Week 24 in air trapping at FRC, the ventilation/perfusion ratio (iV/Q) at TLC, peripheral airway resistance as heterogeneity between 5 Hz and 20 Hz (R5–20) and peripheral compliance as reactance area (AX) using AO (Thorasys Tremoflo), mucus plugging, and pre-bronchodilator FEF 25–75%. These results were consistent across all populations evaluated, suggesting enhanced potential for dupilumab to achieve efficacy in moderate-to-severe asthma at lower, more tolerable doses. 

On February 24, 2024, Sanofi, in collaboration with Regeneron, revealed topline results from the Vestige Phase IV clinical trial evaluating the effect of Dupixent (dupilumab) on airway remodeling parameters through the use of functional respiratory imaging (FRI) in adults with uncontrolled moderate-to-severe asthma with an eosinophilic phenotype or with oral corticosteroid dependent asthma in a late-breaking poster session at the 2024 American Academy of Allergy, Asthma, and Immunology (AAAAI) Annual Meeting.

Apart from asthma, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase III trials, including chronic pruritus of unknown origin, chronic obstructive pulmonary disease (COPD) with evidence of type 2 inflammation, and bullous pemphigoid. 

In conclusion, the emergence of dupilumab represents a promising advancement in the treatment of moderate-to-severe asthma. Dupilumab produced clinically relevant improvements in measures of SAD, including peripheral lung resistance and compliance, forced mid-expiratory flow, along with ameliorated ventilation/perfusion and mucus plugging. These findings suggest that dupilumab has a positive impact on mucus-related aspects of asthma and lung function.