Reata Pharmaceuticals Inc. is seeking FDA approval for its drug bardoxolone methyl after results from phase 3 trials of the CARDINAL study showed patients with chronic kidney disease caused by Alport syndrome had a statistically significant improvement compared to placebo in mean retained eGFR.
“Based on these positive results, and subject to discussions with regulatory authorities, the company plans to proceed with the submission of regulatory filings for marketing approval in the United States and internationally,” the company said in a press release.
Reata said Bardoxolone treatment was generally reported to be well-tolerated and showed a similar safety profile to the phase 2 portion of the CARDINAL study.
“The first-year results from the CARDINAL study are very promising,” Lisa Bonebrake, executive director of the Alport Syndrome Foundation, said in the release. “This provides hope to the entire Alport syndrome community that we could finally have the first therapy to treat this rare, genetic kidney disease.”
The phase 3 portion of CARDINAL enrolled 157 patients with Alport syndrome at approximately 50 study sites in the United States, Europe, Japan and Australia, Reata reported. Patients were randomized 1:1 to either bardoxolone or placebo.
In the trials, patients treated with bardoxolone had a statistically significant improvement after 48 weeks of treatment compared to placebo in mean eGFR of 9.50 mL/min/1.73 m2. Patients treated with bardoxolone experienced a statistically significant increase from baseline in mean eGFR of 4.72 mL/min/1.73 m2, while patients treated with placebo experienced a statistically significant decline from baseline in mean eGFR of -4.78 mL/min/1.73 m2.
Patients’ retained eGFR was also assessed at week 52, after 48 weeks of treatment and 4 weeks of drug withdrawal. At week 52, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean retained eGFR of 5.14 mL/min/1.73 m2. Patients treated with bardoxolone experienced a non-significant decline from baseline in mean retained eGFR of -0.96 mL/min/1.73 m2, while patients treated with placebo experienced a statistically significant decline from baseline in mean retained eGFR of -6.11 mL/min/1.73 m2.
Similar efficacy at week 48 and week 52 of the trial was observed across multiple subgroups, including among pediatric patients, the company said.
After 52 weeks, patients who completed the first 48 weeks of treatment were restarted on the study drug with their original treatment assignments and will continue on the drug for a second year. The second year on-treatment eGFR will be measured after 100 weeks of treatment and the retained eGFR will be measured at week 104 after withdrawal of drug for 4 weeks, the company said.
The FDA “has provided the company with written guidance that, in patients with CKD caused by Alport syndrome, an analysis of retained eGFR demonstrating an improvement vs. placebo after 1 year of bardoxolone treatment may support accelerated approval and an improvement vs. placebo after 2 years of treatment may support full approval,” according to the release.
The drug is also being studied in five other forms of CKD, all with different underlying pathologies.