The Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for bardoxolone (Reata Pharmaceuticals) for the treatment of patients with chronic kidney disease (CKD) caused by Alport syndrome.
Alport syndrome is a rare, genetic disorder characterized by CKD caused by mutations in the genes encoding type IV collagen. Bardoxolone is an activator of nuclear factor erythroid-related factor 2 (Nrf2) that induces molecular pathways that promote restoration of mitochondrial function, reduction of oxidative stress, and inhibition of pro-inflammatory signaling.
The NDA submission includes data from the double-blind, placebo-controlled, randomized, phase 3 CARDINAL trial (ClinicalTrials.gov: NCT03019185) that evaluated the efficacy and safety of bardoxolone in 157 patients with CKD caused by Alport syndrome. Patients were randomly assigned 1:1 to receive bardoxolone or placebo orally once daily. The primary endpoint was the change from baseline in eGFR after 100 weeks of treatment.
Results showed that in the intent-to-treat (ITT) population (eGFR values for patients who either remained on or discontinued the study drug), treatment with bardoxolone was associated with a statistically significant improvement in kidney function vs placebo (mean change from baseline in eGFR at week 100: 7.7mL/min/1.73m2 [P =.0005]). In the modified ITT analysis (excluding eGFR values for patients who discontinued treatment), patients treated with bardoxolone had a mean change from baseline in eGFR of 11.3mL/min/1.73m2 vs placebo (P <.0001). Treatment with bardoxolone also demonstrated a statistically significant improvement in eGFR at week 104 (4 weeks after the last dose). The most common adverse events reported with treatment included muscle spasms and increased aminotransferases.
“We are pleased with the FDA’s decision to accept for filing our NDA for bardoxolone and look forward to continuing to work with the Division during the review process,” said Warren Huff, Reata’s President and CEO. “If approved, bardoxolone may be the first therapy to slow the progression of kidney disease in patients with this serious and debilitating disease.”
A Prescription Drug User Fee Act target date of February 25, 2022 has been set for the application.
The Company is also investigating bardoxolone for the treatment of patients with autosomal dominant polycystic kidney disease, IgA nephropathy, type 1 diabetic CKD, focal segmental glomerulosclerosis, and CKD at meaningful risk of progression to end-stage kidney disease in phase 2 and 3 clinical trials.
- Reata announces FDA accepted for filing the NDA for bardoxolone for the treatment of patients with chronic kidney disease caused by Alport syndrome. [press release]. Plano, TX: Reata Pharmaceuticals, Inc.; April 26, 2021.
- Reata Announces Positive Results From Year 2 of the Pivotal Phase 3 CARDINAL Study of Bardoxolone Methyl in Patients with Alport Syndrome. [press release]. Plano, TX: Reata Pharmaceuticals, Inc.; November 9, 2020.