Professor Marc Humbert, one of the world’s leading specialists in pulmonary arterial hypertension (PAH), has been awarded the prestigious Inserm Grand Prize in recognition of his extraordinary career dedicated to understanding and treating this life-threatening disease. Inserm is the French National Institute of Health and Medical Research.
From Orphan Disease to Hope
When Prof. Humbert began his career 30 years ago, pulmonary arterial hypertension was considered an “orphan disease”—no known causative genes, no specific treatments, and patients facing death within three years of diagnosis. The only options were vasodilators and lung transplantation. Today, thanks largely to his work, pulmonary arterial hypertension is no longer orphan, with multiple treatment options and significantly improved survival rates.
Building the Foundation for Research
After completing his specialized pulmonology studies and a transformative postdoctoral internship in London studying bronchial inflammation, Humbert returned to France determined to explore the mechanisms of pulmonary arterial hypertension in depth. He established comprehensive research infrastructure including:
- One of the world’s largest pulmonary hypertension registries with over 18,000 cases at Bicêtre Hospital (AP-HP)
- Extensive biobanks containing lung tissue explants, biopsies, blood samples, and clinical and genetic data
- A reference center for rare respiratory diseases, designated in 2004
Groundbreaking Discoveries
Humbert was among the first researchers to identify the critical role of inflammation in pulmonary hypertension—a theory initially met with skepticism at conferences where he was “often placed last on the program.” His persistence paid off with several major discoveries:
- Vascular remodeling: Demonstrated that dysfunction of the inner vessel layer (endothelium) is the starting point for disease progression, involving inflammatory cell recruitment and release of cytokines and growth factors
- Genetic basis: Showed that some pulmonary arterial hypertension patients have mutations in the BMPR2 gene, which regulates cell proliferation and survival in lung vessel lining
- Treatment pathway: Identified that BMPR2 dysfunction leads to activin overexpression, contributing to abnormal cell proliferation
Revolutionary Treatment: Sotatercept
These discoveries led to development of sotatercept, a completely new treatment approach. Working with U.S. startup Acceleron Pharma, Humbert helped design clinical trials for artificial proteins that block activin’s biological action.
The results, published in March 2025, were so impressive that an independent committee requested early trial discontinuation so control group patients could access the drug. Sotatercept, when added to standard pulmonary arterial hypertension treatment, significantly:
- Reduced risk of death and lung transplantation
- Decreased clinical worsening events requiring hospitalization
- Improved exercise capacity and functional class
- Increased hemoglobin levels (oxygen supply)
Prof. Humbert notes with relief that “the treatment was generally well tolerated in the various clinical trials,” though vigilance about long-term tolerability remains important.
Collaborative Excellence
Leading the Pulmonary Hypertension Physiopathology and Therapeutic Innovation unit with colleague Christophe Guignabert, Prof. Humbert emphasizes the power of interdisciplinary collaboration. His team brings together specialists from Inserm, Paris-Saclay University, AP-HP, and Marie-Lannelongue Hospital, including biologists, engineers, doctors, surgeons, and health AI specialists.
He is equally emphatic about the essential role of patient organizations: “We have grown together, they really support us in our research.” Some patients have become friends, providing constant motivation for his work.
Looking Forward
Now serving as researcher, clinician, and Dean of the Paris-Saclay Faculty of Medicine, Prof. Humbert continues his mission with undiminished enthusiasm. His current project, Destination 2024, focuses on early diagnosis of pulmonary hypertension caused by pulmonary embolism sequelae, using imaging, AI, biology, innovative drug therapies, and interventional angioplasty approaches.
Upon learning of the Inserm Grand Prize, his thoughts immediately went to his family and “the extraordinary chain of solidarity of patients and their carers: thanks to them, there are now new solutions for managing a disease that remains serious but is no longer orphan.”
The Alliance for Pulmonary Hypertension is deeply honoured to have Prof. Humbert serving on our Scientific Committee. His expertise, leadership, and unwavering commitment to patients continue to guide our mission to improve outcomes for pulmonary hypertension patients across Europe. His journey from a young doctor impressed by the human connections in pulmonology to a world-renowned researcher exemplifies the transformative power of dedication, collaboration, and hope in rare disease research.
The route continues. As Prof. Humbert reminds us: a cure must be found for pulmonary arterial hypertension.