Bardoxolone methyl, Reata Pharmaceuticals’ treatment candidate for pulmonary hypertension (PH), improves exercise capacity and has a safe profile in patients with PH associated with interstitial lung disease (ILD), according to top-line results from a Phase 2 clinical trial.
ILD is a group of several lung conditions that includes idiopathic pulmonary fibrosis (IPF) and sarcoidosis. Reata decided to conduct exploratory studies in patients with ILD after similar clinically meaningful improvements in exercise capacity – assessed through the six-minute walk distance (6MWD) test – were previously observed in patients with PAH associated with connective tissue disease (CTD).
The LARIAT study (NCT02036970) is evaluating the safety and efficacy of bardoxolone methyl in improving 6MWD in about 165 adult patients, including those with PH associated with ILD. No available therapies for PAH have shown efficacy and safety in patients with PH and ILD, Reata observed.
Changes in the six-minute walking test from baseline were analyzed following a 16-week treatment period. Eight patients whose PH is associated with IPF and 25 whose disease is associated with sarcoidosis were randomly assigned to either bardoxolone methyl or placebo treatment.
Treatment with bardoxolone methyl led to a significant increase in 6MWD from baseline of 38 meters in IPF patients and of 17 meters in those with sarcoidosis. Results from both of these groups contrasted with the non-significant changes seen in placebo-treated patients (17 and 9 meters, respectively).
“An estimated one half of IPF patients develop pulmonary hypertension, and these patients have rapidly progressive disease and poor outcomes. The magnitude in six-minute walk distance increases observed in IPF patients is as large as the increases we observed in CTD-PAH patients in our Phase 2 LARIAT study,” Colin Meyer, MD, CMO at Reata, said in a press release.
“We are encouraged by these initial results, especially those in IPF patients, and they support our ongoing efforts in pulmonary hypertension. Once we complete our other ongoing Phase 2 trials, we will evaluate all available data from our mid-stage trials to determine prioritization and timing for this and our other programs,” Meyer added.
In February 2018, the company reported that treatment with bardoxolone methyl in the LARIAT trial improved PH patients’ kidney function over two years without adverse outcomes. Loss of kidney function is a predictor of mortality and all-cause hospitalization in PH patients. LARIAT is due to conclude in September.
Bardoxolone methyl is an oral, once-daily antioxidant inflammation modulator. It activates Nrf2, a protein that induces molecular pathways that protect against oxidative damage due to inflammation and injury.
The FDA granted bardoxolone methyl orphan drug status for the treatment of PAH and Alport syndrome. The compound is currently being studied in the CATALYST Phase 3 study (NCT02657356) in CTD-PAH patients, and in the CARDINAL Phase 2/3 trial (NCT03019185) in Alport syndrome.