Irving-based Reata Pharmaceuticals, a privately held company aiming to translate the company’s groundbreaking research into new therapies, has enrolled the first patient in a Phase 2 dose-ranging study that will examine the safety, tolerability, and efficacy of bardoxolone methyl in patients with pulmonary arterial hypertension (PAH).
Pulmonary hypertension involves high blood pressure in the arteries of the lungs. The American Lung Association describes PAH as a form of pulmonary hypertension caused by the abnormal functioning of pulmonary arteries, which carry blood from the heart to the lungs. A life-threatening disease that affects around 15 to 20 thousand people in the United States, PAH has no cure, but there are several treatment options, all with the purpose of reducing the heart’s workload by allowing blood to flow more easily through the pulmonary arteries.
Available treatments for PAH can either relax the muscles and reduce abnormal cell growth in blood vessels, prevent blood clots in the lungs, reduce constriction in the pulmonary arteries, reduce shortness of breath, reduce the volume of blood the heart must pump, or help it pump more forcefully.
None of the current treatments, however, directly suppress inflammation or proliferation pathways and, consequently, the disease continues to progress, resulting in a 60 to 80 percent mortality rate within just five years of diagnosis for PAH patients.
Research led by both academics and Reata scientists has demonstrated that bardoxolone methyl and related compounds have highly potent antioxidant and anti-inflammatory properties, including beneficial effects on endothelial dysfunction, as well as anti-proliferative and anti-fibrotic effects.
Dr. Colin Meyer, Reata’s Chief Medical Officer, explained in a recent press release that bardoxolone methyl works as an antioxidant inflammation modulator (AIM) to restore endothelial function and suppress vasoconstrictive endothelia signaling, therefore promoting normal vasodilatory tone. Additionally, he noted, the compound complements available PAH therapies through inhibition of pro-inflammatory NF-κB signaling, directly suppressing inappropriate proliferation, which is not directly affected by currently approved therapies.
In addition, Nrf2 activation has been found to positively regulate mitochondrial function, promoting increased cellular energy production.
Reata’s new clinical trial is a multi-center, double-masked, randomized, dose-ranging, placebo-controlled study. The primary efficacy endpoint is a six minute walk test. The study will also explore changes from baseline in cardiopulmonary exercise testing, cardiac magnetic resonance imaging, parameters collected during Doppler echocardiography and other measures.