Volume 19: Issue 2

Editor's Memo

Deborah Jo Levine, MD

Professor of Medicine, Pulmonary and Critical Care, Medical Director Lung Transplantation, Director of Pulmonary Hypertension, University of Texas Health Science Center San Antonio, San Antonio, TX

It is a great pleasure to introduce this issue's Guest Editors of Advances in Pulmonary Hypertension. Drs Mark Nicolls and Marc Humbert lead an elite group of experts in a timely compilation on drug development and clinical trials in pulmonary hypertension (PH).

The opening article by Drs Martin Wilkins and Marlene Rabinovitch eloquently illustrates novel exciting targets for drug development. These targets are based on the

The current treatments for pulmonary arterial hypertension (PAH) relieve symptoms and may slow the course of the condition but are challenged by the underlying vascular pathology. New treatments are required to arrest and reverse PAH. Here we review a number of exciting candidates based on our understanding of the mechanisms driving the condition.

Despite advances in our understanding of the disease, significant therapeutic gaps remain for pulmonary arterial hypertension (PAH). Indeed, no cure exists yet for this devastating disease, and very few innovative therapies beyond the traditional pathways of endothelial dysfunction have reached late clinical trial phases in PAH. While there are inherent limitations to the currently available animal models of PAH, the delayed translation of innovative therapies to the clinic may also relate to flawed preclinical research methodologies. The present article discusses the limitations and flaws in the design of preclinical PH trials and discusses opportunities to create preclinical studies with improved predictive value in identifying key mechanisms involved in PAH development and progression and guiding early phase drug development in PAH patients. The implementation of rigorous study design will need support not only from researchers, peer reviewers, and editors, but also from academic institutions, funding agencies, and animal ethics authorities.

This May, Guest Editors Marc Humbert, MD, PhD, Director of the French Pulmonary Hypertension Reference Center, and Professor of Medicine at Paris-Saclay University, Le Kremlin-Bicêtre, France, and Mark Nicolls, MD, Professor of Medicine, Pulmonary, Allergy, and Critical Care Medicine at Stanford University School of Medicine in Stanford, California, held a discussion with Norman Stockbridge, MD, PhD, Director of the Division of Cardiology and Nephrology in the Office of Cardiology, Hematology, Endocrinology, and Nephrology at the Center for Drug Evaluation and Research, US Food and Drug Administration in Silver Spring, Maryland, and Roham Zamanian, MD, Associate Professor of Medicine and Director,

Pulmonary arterial hypertension (PAH) is a rare, progressive disease. There are 11 drugs available in the United States to treat adult PAH patients; however, all drugs primarily act through vasodilation and have modest effects on clinical endpoints. None of these drugs can claim survival benefit in their product labels. New drugs are needed that target other mechanisms in the disease to have durable benefits for patients. To demonstrate clinical benefit, new drugs are now tested in large, randomized, placebo-controlled trials evaluating their effect to delay clinical worsening, a composite endpoint of morbidity events and death. Efficient clinical trial designs, such as the use of enrichment strategies, that reduce the number of patients and trial duration would be valuable for this disease. It would also be desirable to have new clinical endpoints that measure improvement in quality of life and allow the use of extrapolation strategies to the pediatric population. Academic, industry, and regulatory partnerships are key to advancing therapies for this disease.

Full Issue PDF

Memos

Editor's Memo

Novel and Relevant Mechanistic Pathways

Limitations and Flaws of Preclinical Pulmonary Hypertension Studies

Pulmonary Hypertension Roundtable: Drug Development and Negative Clinical Trial Results

Patient Perspective: Going Through a Clinical Trial

Ask the Expert: A Regulatory Perspective on Clinical Trials for Pulmonary Arterial Hypertension

Conference Abstracts

Guest Editor’s Memo

A Roundtable Discussion Addressing Patient-Centered Care and Quality of Life in Patients With Pulmonary Arterial Hypertension

Editor’s Memo

Pulmonary Hypertension Associated With Parenchymal Lung Disease