Bardoxolone methyl, an investigational therapy developed by Reata Pharmaceuticals, was shown to significantly improve the exercise capacity of patients with pulmonary hypertension (PH) associated with sarcoidosis in a Phase 2 clinical trial.
Bardoxolone is an experimental, oral molecule that promotes the resolution of inflammation by targeting an important mediator of cell responses called Nrf2. Nrf2 is responsible for regulating biological processes such as oxidative damage, inflammation, and fibrosis.
Sarcoidosis affects multiple organs, mostly the lymph nodes and lungs. Due to the inflammatory nature of sarcoidosis, bardoxolone methyl represents a promising treatment option.
In the Phase 2 clinical trial called LARIAT (NCT02036970), bardoxolone is being tested as a treatment for several lung diseases associated with PH, including sarcoidosis, idiopathic pulmonary fibrosis (IPF), connective tissue disorder, idiopathic interstitial pneumonia, and others.
The LARIAT trial evaluated the therapy’s effect on the exercise capacity of 25 sarcoidosis patients, assessed by the six-minute walk distance (6MWD) test. These patients were treated with bardoxolone or a placebo for a period of 16 weeks.
After the treatment period, sarcoidosis patients taking bardoxolone demonstrated a significant increase in the 6MWD test of 17 meters, compared to baseline. In contrast, the placebo-treated patients showed an insignificant increase of 9 meters in the 6MWD test.
Bardoxolone-treated IPF patients also improved their results on the 6MWD test by walking 38 meters more than before treatment, whereas placebo-treated patients had an insignificant reduction of 13 meters.
The trial also initially resulted in a positive safety and tolerability profile for bardoxolone, with no new safety issues reported.
“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 trial, we will evaluate all available data from our mid-stage trials to determine prioritization and timing for this and our other programs” Colin Meyer, Reata’s chief medical officer, said in a press release.
Bardoxolone is also being studied as a potential therapy for Alport syndrome in the Phase 3 CARDINAL (NCT03019185) study, and as a treatment for connective tissue disease associated with pulmonary arterial hypertension (CTD-PAH) in the Phase 3 CATALYST (NCT02657356) trial.
The U.S. Food and Drug Administration has granted orphan drug designation to bardoxolone as a treatment for PAH and Alport syndrome.