Reata Pharmaceuticals, a biopharmaceutical company based in Irving, Texas, recently released a report on the initial findings of the LARIAT clinical trial assessing bardoxolone methyl — an oral, once daily antioxidant inflammation modulator (AIM) — as a treatment for pulmonary arterial hypertension (PAH). The data were presented by Professor of Medicine Dr. Ronald Oudiz from the David Geffen School of Medicine at UCLA during the 2015 American College of Chest Physicians (CHEST 2015) in Montreal, Canada, with the title, “Initial Data Report from ‘LARIAT’: a Phase 2 Study of Bardoxolone Methyl in PAH Patients on Stable Background Therapy.”
Slides for the presentation are available for viewing and download here.
Patients enrolled in the LARIAT trial maintained stable background PAH treatment at baseline and for the duration of the study. Efficacy analyses demonstrated the drug’s therapeutic effect, as assessed by improved 6-minute walk distance (6MWD), with treatments of 2.5 to 10 mg at 16 weeks. Treatment with bardoxolone methyl was also found to improve metabolic parameters, in particular to induce a weight loss of up to 3 kg compared to placebo, and a decrease in creatine kinase — a known indicator of muscle inflammation. Researchers also noted the drug’s efficacy in patients with connective tissue disease associated PAH (CTD-PAH), as evidenced by an average increase in 6MWD of 30 meters from baseline.
Reata researchers also determined bardoxolone methyl’s safety profile to be favorable, with LARIAT participants reporting mild, transient adverse effects and, unlike previous cohorts with advanced kidney disease, did not experience any fluid retention.
“The initial data from LARIAT are very encouraging and indicate that bardoxolone methyl’s novel mechanism of action may provide a new approach to PAH therapy. Clinically, these effects may acutely translate to increased muscular function, and as we have observed in preclinical models, may reduce pathological cardiovascular remodeling in the long-term,” said Colin Meyer, M.D., Reata’s Chief Medical Officer, in a press release. “This pharmacology is particularly meaningful to PAH patients with connective tissue disease. These patients have autoimmune disease that causes their PAH, and their inflammatory disease processes often involve more remodeling than other subtypes. This explains why these patients often do not respond well to approved vasodilator therapy relative to idiopathic PAH patients and represent a subset of the PAH population with significant unmet need. On the basis of these data and recent interactions with the FDA, we are excited to announce that we are planning to initiate a phase 3 study of bardoxolone methyl in patients with CTD-PAH in 2016.”