Research highlights
Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.
Dr. Andrew J. Sweatt
Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.
“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference
“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.
Dr. Anna R. Hemnes
Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”
Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.
The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.
In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”
Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.