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

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.