Inserm Grand Prize 2025: Marc Humbert, thirty years of innovation against pulmonary hypertension
On Thursday 27 November, the Inserm Grand Prize was awarded to professor Marc Humbert for his entire career, devoted to deciphering the mechanisms of pulmonary arterial hypertension (PAH). From characterising the disease to developing innovative therapies, his work carried out within the laboratory Pulmonary Hypertension: Pathophysiology and Therapeutic Innovation (Univ. Paris-Saclay/Inserm) has paved the way to more precise and more effective treatments for thousands of patients.
Dean of the Faculty of Medicine at Université Paris-Saclay, director of the unit Pulmonary Hypertension: Pathophysiology and Therapeutic Innovation (HPPIT - Univ. Paris-Saclay/Inserm), head of the department of pulmonology and respiratory intensive care at Bicêtre Hospital (AP-HP), and a world specialist in pulmonary arterial hypertension (PAH) (see box), Marc Humbert has devoted more than thirty years to understanding and treating this long-considered orphan disease. Trained at Université Paris-Sud (now Université Paris-Saclay) and at Antoine-Béclère Hospital (AP-HP), he very early turned towards research in pulmonology. Between 1993 and 1995, he completed his postdoctoral fellowship at Imperial College London, where he acquired the cellular and molecular tools that would permanently shape his future investigations.
Upon his return to France, he set up a large database and a collection of lung tissue from patients with PAH or other forms of pulmonary hypertension, bringing together biological samples and patient-related clinical and genetic data. At the same time, within the department he heads at Bicêtre Hospital, he co-founded, together with Gérald Simonneau and Olivier Sitbon, professors of pulmonology at Université Paris-Saclay, one of the world’s largest pulmonary hypertension registries, with over 18,000 cases recorded, and allowing robust epidemiological studies and better patient follow-up.
Major therapeutic innovations
Marc Humbert was also one of the first to explore the role of inflammation in PAH. His work has demonstrated that vascular remodelling begins with endothelial dysfunction, which activates a cascade of reactions. It has also shed light on the role of BMPR2 gene mutations in the disease.
These discoveries have led to major therapeutic innovations. In collaboration with Acceleron Pharma, a US biopharmaceutical company, he contributed to the development of sotatercept, the first treatment targeting and inhibiting activin, a hormone with numerous functions in the body and in the pulmonary vessels. International clinical trials have shown a reduction in the risk of mortality, hospitalisation and clinical worsening in severe PAH. This advance represents a turning point in the management of a disease with a particularly poor prognosis.
Throughout his career, Marc Humbert has authored more than 1,000 publications and has helped shape evolving therapeutic strategies in pulmonology. The excellence of his work has been recognised by numerous distinctions, including the Grand Prize of the European Respiratory Society (2024), the André Cournand Prize (European Respiratory Society, 2006), the Descartes-Huygens Prize (Royal Netherlands Academy of Arts and Sciences, 2009) and the Eliane and Gérard Pauthier Prize for research on rare diseases (Fondation des Maladies Rares under the aegis of the Fondation de France, 2016).
With the 2025 Inserm Grand Prize, an entire visionary scientific career is being honoured, the career of a Professeur des universités-praticien hospitalier who has profoundly transformed the field of pulmonary hypertension and continues to lead the way to a clear objective: curing PAH.
Pulmonary arterial hypertension (PAH) is a rare lung disease affecting several thousand people each year in France. It is characterised by increased blood pressure in the pulmonary arteries, which become obstructed due to the contraction and progressive accumulation of cells in the vessel wall. This places a strain on the heart, which may eventually fail to function normally. Without effective treatment, patients develop progressive breathlessness on exertion and then at rest, along with dizziness and fainting.