Phase 2 Results Show Increased Kidney Function in Alport Patients

Today, an update on the ongoing Phase 2 CARDINAL study was provided by biopharmaceutical company Reata Pharmaceuticals, Inc.

The study is evaluating bardoxolone methyl (bardoxolone) in patients with chronic kidney disease (CKD) because of Alport syndrome; the Phase 2 portion enrolled 30 patients to receive the drug orally, once-daily for 2 years.

CARDINAL is a Phase 2/3 study enrolling patients from 12 to 60 years old with an established genetic or histological diagnosis of Alport syndrome, baseline estimated glomerular filtration rate (eGFR) values between 30 to 90 mL/min/1.73 m², and on stable renin-angiotensin-aldosterone system blockade unless contraindicated.

The Phase 2 portion is open-label and enrolled 30 patients, while the Phase 3 portion is double-blind, placebo-controlled, and will randomize an estimated 150 patients on a 1:1 basis to once-daily, oral bardoxolone or placebo.

Ninety percent of patients (n=27) remain on study and will be included in the Week 52 withdrawal analysis.

Efficacy results have exhibited significant and sustained increases in kidney function as measured by eGFR maintained through Week 36. The mean improvement from baseline in eGFR at Week 36 is 11.3 mL/min/1.73 m² (n=27; p<0.000001), which is not meaningfully unlike the change observed at Week 12. Initial increases in the urinary albumin-to-creatine ratio that were the result of increases in eGFR have stabilized.

“Bardoxolone continues to be well-tolerated in Alport syndrome patients as evidenced by the encouraging safety profile and high patient retention rate in the Phase 2 cohort of CARDINAL,” said Colin Meyer, MD, Chief Medical Officer of Reata in a press release. “These data demonstrate that the clinically meaningful increases in kidney function we observed in Alport syndrome patients after 12 weeks of treatment are durable for at least 36 weeks and consistent with our observations from prior trials of bardoxolone in other forms of CKD. We appreciate the interest and commitment of the Alport syndrome patient community and CARDINAL investigators to advance our understanding of bardoxolone in these patients with unmet need.”

Adverse events (AEs) throughout the study have been generally mild to moderate in severity, and no drug-related serious AEs have been reported.

On-treatment eGFR change from baseline in bardoxolone-treated patients relative to placebo at Week 48 serves as the primary efficacy endpoint in the Phase 3 portion of CARDINAL. The key secondary endpoint is the change from baseline in retained eGFR benefit after 48 weeks on-treatment and 4 weeks off-treatment. It is designed to demonstrate that the drug has disease-modifying activity in this indication.

After withdrawal, patients will be restarted on bardoxolone with their original treatment assignments and will continue for a second year, in which eGFR change will be measured after 100 weeks, and the retained eGFR benefit will be measured after withdrawal of the drug for 4 weeks at Week 104.

Reata hopes that the year-2 retained eGFR benefit will support full approval for the drug from the U.S. Food and Drug Administration (FDA).

For more on studies pertaining to the rare disease community, follow Rare Disease Report on Facebook and Twitter.