Topline results from the Phase 2 PHOENIX trial with Reata Pharmaceuticals’ bardoxolone methyl continue to demonstrate its potential to improve the outcome of patients with rare forms of chronic kidney diseases (CKD), including Alport syndrome and type 1 diabetic CKD.
The PHOENIX study (NCT03366337) is assessing the safety and efficacy of bardoxolone methyl in rare renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), focal segmental glomerulosclerosis, IgA nephropathy, and chronic kidney disease associated with type 1 diabetes.
Still recruiting, the study is designed to evaluate the potential of orally administrated, once-daily bardoxolone methyl after 12 weeks of treatment in approximately 100 patients with these rare kidney diseases.
Results from the IgA nephropathy and type 1 diabetes CKD groups of the PHOENIX study showed that the treatment can promote significant changes from baseline in a patient’s kidney function, as determined by the estimated glomerular filtration rate (eGFR; the higher the score, the better the kidney function).
More specifically, in 26 patients with IgA nephropathy, treatment with bardoxolone led to a significant increase in eGFR of 8.0 mL/min/1.73 m2 at week 12 compared to baseline. In 28 patients with type 1 diabetes CKD, the eGFR increase reported was of 5.5 mL/min/1.73 m2 after 12 weeks of treatment.
These changes represented a recovery in average eGFR loss of about six years in the IgA nephropathy cohort and three years in the diabetes CKD cohort, according to the patients’ annual rate of kidney function decline shown at the start of the study. The first cohort had an average annual rate of eGFR loss of 1.2 mL/min/1.73 m2 prior to study entry; the second had an average of 1.9 mL/min/1.73 m2 prior to study entry.
During the PHOENIX study, no serious treatment-related adverse events were reported. Those reported were mostly mild to moderate.
“With these data, bardoxolone has improved kidney function in multiple rare forms of CKD, including Alport syndrome, autosomal dominant polycystic kidney disease, IgA nephropathy, and type 1 diabetic CKD,” Colin Meyer, MD, chief medical officer of Reata, said in a press release.
“The absence of drug-related serious adverse events and the eGFR improvements observed in the rare forms of CKD that we have studied suggest that bardoxolone has the potential to become an effective therapy for multiple rare forms of CKD,” Meyer said.
Bardoxolone methyl, formerly known as RTA 402, is being developed by Reata to trigger signaling pathways that help reduce inflammation by restoring cells’ powerhouses (mitochondria) to normal activity and to reduce oxidative stress, issues common in several diseases.
Bardoxolone has received orphan drug status from the European Commission and the U.S. Food and Drug Administration to treat patients with Alport syndrome. These designations are expected to support and expedite the therapy’s development, regulatory review, and approval.
The safety and efficacy of bardoxolone in Alport syndrome is currently being investigated in the ongoing Phase 2/3 CARDINAL trial (NCT03019185). Results from the Phase 2 part announced in July 2018 revealed that one year of treatment with the investigational drug has the potential to reverse the damaging effects of Alport syndrome, promoting the recovery of kidney function.
Reata is recruiting participants for the Phase 3 part of the study, expected to enroll up to 180 Alport patients across more than 60 sites worldwide. Participants will randomly receive either oral bardoxolone methyl or a placebo for one year.
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