Pulmonary arterial hypertension (PAH) is a condition characterized by high blood pressure in the pulmonary arteries that carry blood from the heart to the lungs. Recent advancements in PAH treatments, demonstrating significant physiological and clinical improvements, have generated interest in achieving long-term disease control and potentially disease modification. While the term “disease modification” is used in other chronic conditions to describe therapies targeting the underlying disease, its application in PAH is debated due to the lack of clear biomarkers and trial designs. Consequently, regulatory agencies are shifting focus from disease modification and are instead prioritizing trials showing strong pathophysiological effects, like reverse pulmonary vascular remodeling, which holds promise for stronger clinical responses, remission, and potential cures. To address these challenges, researchers, including the CVC’s Dr. Jason Weatherald, published a Personal View in Lancet Respiratory Medicine, aiming to define disease modification and establish criteria for partial and full remission in PAH.
Despite ongoing interest in disease modification, stakeholders—including patients, physicians, and regulators—prioritize strong evidence of pathophysiological changes in phase 2 trials, and demonstrable, sustained benefits for patients in larger phase 3 trials. The authors underscore the significance of establishing reverse remodeling in phase 2 trials of novel PAH therapies, given the expectation of more substantial and durable hemodynamic and clinical improvements compared to current treatments.
Although current PAH treatments enhance outcomes and offer the prospect of clinical improvement beyond just slowing disease progression, they still don’t achieve remission or cure. While future research and new biomarkers could enable the observation of direct treatment effects on the disease’s course and outcomes, regulatory agencies are currently unlikely to grant special status to existing or new treatments. The authors advocate for future research into these biomarkers and trial designs, but also underscore that achieving remission should remain an important objective given its significant impact on patient survival and quality of life.
