Reata Pharmaceuticals has reported positive interim results from the extension Phase 2 LARIAT clinical trial assessing bardoxolone methyl for the treatment of pulmonary arterial hypertension (PAH). The LARIAT trial is assessing the efficacy, safety, and tolerability of bardoxolone methyl compared to a placebo in patients with PAH.
The study aims to determine the recommended dose range, assessing the change from baseline in a six-minute walking distance (6MWD, a test for exercise capacity), and to determine the effect of the drug in PAH associated with connective tissue disease, interstitial lung disease, and from unknown causes. The unknown causes includes subsets of patients with WHO Group 3 or WHO Group 5 pulmonary hypertension following 16 weeks of treatment.
All patients taking part in the trial were on stable doses of background PAH therapies at baseline and during the study period.
The new interim results demonstrated that following 32 weeks of treatment with bardoxolone methyl, the previously reported increase in 6MWD at 16 weeks was sustained. Through week 32, the data showed that patients with connective tissue disease (CTD)-associated PAH treated with bardoxolone methyl also had similar sustained increases in 6MWD.
Treatment with bardoxolone methyl was found to be well-tolerated, and patients had fewer adverse events during the extension study than during the first 16 weeks of treatment.
The U.S. FDA has granted orphan drug designation to bardoxolone methyl for the treatment of PAH. It is an oral, once-daily antioxidant inflammation modulator.
“We are pleased that the interim data demonstrate that the clinically meaningful improvements in 6MWD noted through 16 weeks of treatment are sustained through 32 weeks of treatment,” said Colin Meyer, M.D., Reata’s chief medical officer, 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.”
PAH is a life-threatening disease involving endothelial dysfunction, vasoconstriction in small pulmonary arteries, aberrant proliferation of certain vascular cells, and dysregulated inflammatory signaling leading to vascular remodeling, pulmonary fibrosis, and right ventricular enlargement.
PAH has been estimated to affect 15,000 to 20,000 people in the U.S., mostly middle-aged women. Available treatments for PAH can provide improvements in symptoms, primarily by relieving vasoconstriction — inhibiting signaling in the endothelin-1 pathway — but they do not directly suppress inflammation or proliferation pathways, and the disease continues to progress.