The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Reata Pharmaceuticals regarding the New Drug Application (NDA) for bardoxolone for the treatment of patients with chronic kidney disease (CKD) caused by Alport syndrome.

The NDA, which was reviewed by the FDA’s Cardiovascular and Renal Drugs Advisory Committee, included data from the phase 3 CARDINAL trial (ClinicalTrials.gov Identifier: NCT03019185). The study evaluated the efficacy and safety of bardoxolone, an activator of nuclear factor erythroid-related factor 2, in 157 patients with CKD caused by Alport syndrome.

Findings showed that treatment with bardoxolone was associated with a statistically significant improvement in kidney function (based on change from baseline in eGFR) compared with placebo.  However, the panel noted that the submitted data did not demonstrate that the drug slowed the progression of CKD in these patients. Safety issues including an increased risk of heart failure and increases in albuminuria and blood pressure were also flagged as concerns.

These issues were reiterated in the CRL, which stated that the application for bardoxolone could not be approved in its current form due to a lack of data supporting claims of slowing kidney function loss and reducing kidney failure progression. The Agency requested that additional data be submitted to support the efficacy of bardoxolone, as well as its safety, with particular focus on its effect on the QT interval.

“This outcome is a significant disappointment for our company, as well as the many patients, families, and investigators who have participated in our development program for bardoxolone in Alport syndrome patients,” said Warren Huff, Reata’s Chief Executive Officer. “We will continue to work with the FDA to confirm our next steps on our Alport syndrome program.”

Alport syndrome is a rare, genetic disorder characterized by CKD caused by mutations in the genes encoding type IV collagen.

Reference

Reata Pharmaceuticals receives Complete Response Letter from the FDA for bardoxolone for the treatment of patients with chronic kidney disease caused by Alport syndrome. News release. February 25, 2022. https://www.businesswire.com/news/home/20220225005536/en/Reata-Pharmaceuticals-Receives-Complete-Response-Letter-From-The-FDA-for-Bardoxolone-for-the-Treatment-of-Patients-with-Chronic-Kidney-Disease-Caused-by-Alport-Syndrome