Advancements in Pulmonary Hypertension and Interstitial Lung Disease: Emerging Therapies and Clinical Trial Designs

Pathogenesis and Phenotypes:
Research has identified distinct phenotypes in ILD-PH, characterized by specific presentations, clinical courses, and treatment responses. Genetic anomalies, such as mutations in the BMPR2 gene, have been linked to the development of ILD-PH.

Clinical Trials:
Clinical trials in PAH have led to the approval of several effective treatments that improve symptoms, exercise capacity, and clinical outcomes. Future trials face challenges related to sample size requirements, efficiency, and demonstrating incremental benefit on traditional endpoints in patients receiving background therapy with multiple drugs.

Emerging Therapies:
Innovative clinical trial endpoints, novel trial designs, and emerging technologies such as artificial intelligence are being explored to overcome challenges in PAH clinical trials. These include the use of multicomponent clinical improvement (MCI) endpoints and the validation of surrogate endpoints.

ILD Trials:
The PF-ILD trial, a phase III clinical trial, evaluates the efficacy and safety of nintedanib in patients with progressive fibrosing interstitial lung disease. The trial design includes a double-blind, randomized, placebo-controlled study with a primary endpoint of the annual rate of decline in forced vital capacity over 52 weeks.

Guideline Updates:
Recent guidelines have updated the criteria for diagnosing idiopathic pulmonary fibrosis (IPF) and defined progressive pulmonary fibrosis (PPF). Conditional recommendations have been made for the use of nintedanib in PPF and for further research into pirfenidone.

Industry Developments:
Novartis has ended a mid-stage IPF trial but will continue testing the drug in PAH, indicating ongoing efforts to find effective treatments for these conditions.