Bardoxolone methyl is an investigational, oral, once-daily antioxidant inflammation modulator (AIM). The drug candidate is designed to target the Nrf2 pathway, which is thought to control the transcription of genes that increase cellular antioxidant content and anti-inflammatory mediators. Unlike certain therapies that work as vasodilators, the available preclinical data suggests that bardoxolone methyl might directly target inflammation and mitochondrial dysfunction in PAH.
The LARIAT clinical trial is “A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension,” in which patients were randomized in a 1:3 ratio to be given once-daily doses of either a placebo or bardoxolone methyl over 16 weeks, in the study’s first part. At the end of 16 weeks, those who completed the treatment were eligible to continue to the second part, the open-label, long-term extension phase of the trial.
The study evaluated whether bardoxolone methyl could complement other approved PAH therapies. Researchers assessed the effect of the drug in patients’ exercise capacity by measuring their six-minute walk distance (6MWD) scores. The 6MWD was collected at baseline, and then every four weeks.
Researchers found that the 6MWD scores increased during the 16 weeks of treatment, and were sustained throughout the extension phase until 32 weeks of treatment, without significant differences at 16 and 32 weeks within the same set of patients. Patients with connective tissue disease-associated PAH receiving treatment with bardoxolone methyl had similar sustained increases in 6MWD through week 32.
The drug candidate was found to be well-tolerated, and fewer adverse reactions were reported during the extension study than during the first 16 weeks of treatment.
“We are pleased that the interim data demonstrates that the clinically meaningful improvements in 6MWD noted through 16 weeks of treatment are sustained through 32 weeks of treatment,” said Reata Pharmaceuticals Chief Medical Officer Colin Meyer, M.D., in a press release. “We are planning to submit the data to a scientific meeting and believe the available efficacy and safety data support the continued development of bardoxolone methyl in pulmonary hypertension.”
Bardoxolone methyl is thought to potentially impact several aspects of PAH pathology not addressed by current therapies. The drug was granted orphan drug designation by the U.S. FDA for the treatment of PAH in April 2015.