Investigations of bardoxolone methyl have been conducted by
Reata Pharmaceuticals in a partnership with
Abbvie and
Kyowa Hakko Kirin. The UK based company e-Therapeutics has announced in late 2020 the possible development of Bardoxolone for anti-viral treatment of COVID-19(Coronavirus), and announced a possible phase 3 program to follow (https://www.etherapeutics.co.uk/wp-content/uploads/2021/02/RNAi-Press-Release.pdf accessed 16 Feb 2021).
Phase 1 A
Phase 1 clinical trial, sponsored by Reata, was conducted to determine the safety profile of and appropriate dosing for subsequent phase II studies, as well as to evaluate antitumor activity in patients with advanced solid tumor or lymphoid malignancy. Grade 3 reversible
liver transaminase elevations were reported. The maximum tolerated dose was 900 mg/day.
NQO1 mRNA levels, indicative of
Nrf2 pathway activation, were increased in
peripheral blood mononuclear cells (PBMCs), and tumor biopsies showed decreased levels of
NF-κB and
cyclin D1. An improvement in estimated
glomerular filtration rate (eGFR) in patients treated with bardoxolone methyl was noted, and based on this finding it was suggested by the authors that the drug might be beneficial for patients with CKD.
Phase 2 A Reata-funded,
Phase 2 multi-center
RCT (BEAM) in patients with moderate to severe CKD and type 2 diabetes reported that eGFR was increased (> 10 ml/min/1.73 m2) in patients treated with bardoxolone methyl for 24 months. An analysis of
secondary endpoints showed that approximately three-quarters of bardoxolone methyl-treated patients experienced at least a 10 percent increase in eGFR, and one-quarter of the patients had an improvement of 50%.
Adverse events in bardoxolone methyl-treated patients were generally manageable and mild to moderate in severity, with muscle spasm being reported most frequently. In 2014, Reata announced the initiation of a placebo-controlled, multicenter Phase 2 study (LARIAT), to assess the effects of bardoxolone methyl in pulmonary arterial hypertension. ==Mechanism of action==