Dados do Trabalho

Título

SERALUTINIB IMPROVES PULMONARY ARTERIAL BLOOD VESSEL VOLUME DISTRIBUTION IN PULMONARY ARTERIAL HYPERTENSION (PAH): RESULTS OF THE TORREY PHASE 2 IMAGING SUBSTUDY

Introdução

Seralutinib is a novel, inhaled PDGFRα/ß, CSF1R, and c-KIT kinase inhibitor with anti-inflammatory, antiproliferative, and anti-fibrotic effects, that met the primary endpoint of reduction in pulmonary vascular resistance in the phase 2 TORREY trial in PAH (NCT04456998) and has the potential to treat pulmonary vascular remodeling. This abnormal remodeling includes distal pruning and proximal pulmonary arterial dilation. Quantitative analysis of these features is possible with computed tomography (CT) imaging.

Objetivo

This TORREY substudy evaluated the effects of seralutinib on the pulmonary vasculature after 24 weeks of treatment using quantitative CT imaging.

Método

The TORREY CT substudy used thin-section, volumetric non-contrast chest CTs followed by automated pulmonary vascular segmentation to evaluate the reverse remodeling potential of seralutinib. Baseline and Week 24 blood vessel volumes (BVVs) were determined at distinct levels defined by vessel cross-sectional area (CSA) in 19 subjects on a background of 2-3 approved PAH therapies. BVVs of pulmonary arteries with a CSA <5 mm2 (BV5A) and >10 mm2 (BV10A) were calculated. The BV5A to BV10A ratio (BV510ARATIO) was used to express the relative redistribution of pulmonary arterial BVV. Linear regression was used to model the treatment effect.

Resultados

The BV510ARATIO increased from baseline to Week 24 in the seralutinib group (n=7) vs placebo (n=12; p=0.028), and BV510ARATIO changes correlated with changes in stroke volume (R=0.65, p=0.0033) and pulmonary artery compliance (R=0.56, p=0.016).

Conclusão

In heavily treated patients with PAH, adding seralutinib for 24 weeks led to a significant redistribution of pulmonary arterial BVV to smaller vessels. These data visualize and quantify seralutinib’s treatment effect on the pulmonary arterial vasculature in PAH.

*on behalf of the Seralutinib Steering Committee