Reata Pharmaceuticals announced that pulmonary arterial hypertension (PAH) patients treated with bardoxolone methyl showed significant improvements in kidney function that were sustained for two years without adverse outcomes.
In PAH patients, progressive loss of kidney function is a predictor of mortality and all-cause hospitalization, with patients experiencing an annualized loss of kidney function of approximately 8 to 13 mL/min/1.73 m2.
“Loss of kidney function is common in PAH patients and associated with an increased risk of adverse outcomes and death. Treatments for PAH improve symptoms but often worsen kidney function, placing patients at greater risk,” Daniel W. Coyne, MD, nephrologist and professor of Medicine at Washington University in St. Louis, Missouri, said in a press release.
The LARIAT study enrolled PAH patients already experiencing impaired kidney function, with an average of estimated glomerular filtration rate (eGFR, a marker of kidney function) of 75.6 mL/min/1.73 m2.
In the trial, patients were randomized to a placebo group (30 patients) or to treatment with bardoxolone methyl (71 patients). The treatment lasted for 16 weeks.
Results showed that eGFR was signficantly increased in bardoxolone-treated patients compared to the placebo group – an increase of 10.6 mL/min/1.73 m2 – at the end of the treatment period.
Patients who completed the 16-week treatment were eligible to participate in an open-label extension study with bardoxolone to assess the therapy’s long-term effects.
At the time of the analysis, 55 patients had received bardoxolone for one year and 26 of these patients for at least two years. Both long-term treatments led to signficant improvements in eGFR compared to baseline – 10.7 mL/min/1.73 m2 and 11.3 mL/min/1.73 m2, respectively.
The majority of the patients (88 percent) treated with bardoxolone maintained increases in eGFR above baseline (meaning at the start of the study) after two years of treatment.
“The two-year trial data are the longest available with bardoxolone and suggest raising kidney function with bardoxolone is not harmful and is likely to be beneficial in PAH patients and other disease states,” Coyne said.
These results support earlier observations from Reata’s diabetic chronic kidney disease (CKD) trials – BEAM (NCT00811889) and BEACON (NCT01351675) – in which treatment with bardoxolone methyl led to sustained improvements (for at least one year) in kidney function and reduced by more than half the risk of kidney failure.
The improvements were maintained even after bardoxolone was withdrawn for one month, supporting the therapy’s effects in improving kidney function.
“Through these analyses of long-term clinical data, we have been able to differentiate the improvements in kidney function with bardoxolone from agents that may modestly, transiently, and adversely increase kidney function by increasing blood pressure in the kidney,” said Colin Meyer, MD, Reata’s chief medical officer.
“The longer term data in PAH patients, who are extremely sensitive to any adverse perturbations of renal or cardiac function, provides further evidence that bardoxolone may be beneficial, and not harmful, to the kidney,” Meyer added.
Reata is currently testing bardoxolone methyl as a therapy for several diseases, namely rare forms of CKD, including Alport syndrome, type 1 diabetic CKD, and connective tissue disease-associated PAH, among others.
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