The Food and Drug Administration (FDA)’s Cardiovascular and Renal Drugs Advisory Committee voted 13 to 0 against the approval of bardoxolone 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 that induces molecular pathways that promote restoration of mitochondrial function, reduction of oxidative stress, and inhibition of pro-inflammatory signaling.
The New Drug Application submission included data from the double-blind, placebo-controlled, randomized, phase 3 CARDINAL trial (ClinicalTrials.gov Identifier: NCT03019185), which evaluated the efficacy and safety of bardoxolone in 157 patients with CKD caused by Alport syndrome. Findings from the trial 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. The most common adverse events reported included muscle spasms and increased aminotransferases.
In meeting documents, the FDA panel noted that based on the data submitted, bardoxolone did not appear to be effective at slowing the progression of CKD in patients with Alport syndrome. Safety issues including an increased risk of heart failure and increases in albuminuria and blood pressure were also flagged as concerns.
Although not bound by the committee’s recommendations, the Agency does take them into consideration when making decisions on approval. A Prescription Drug User Fee Act (PDUFA) target date of February 25, 2022 has been set for the application.
“We are disappointed with today’s outcome of the Committee’s vote regarding bardoxolone, an investigational drug with a novel mechanism of action,” said Warren Huff, Reata’s President and CEO. “We believe the scientific evidence supports bardoxolone approval in the US for CKD in patients with Alport syndrome, which is one of the most rapidly progressive forms of CKD. We will continue to work with the FDA to answer any questions they may have.”
The Company is also investigating bardoxolone for 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.
Reata Pharmaceuticals announces outcome of FDA Advisory Committee meeting of bardoxolone for the treatment of patients with chronic kidney disease caused by Alport syndrome. News release. Reata Pharmaceuticals, Inc. Accessed December 9, 2021. https://www.businesswire.com/news/home/20211208006101/en/Reata-Pharmaceuticals-Announces-Outcome-of-FDA-Advisory-Committee-Meeting-of-Bardoxolone-for-the-Treatment-of-Patients-with-Chronic-Kidney-Disease-Caused-by-Alport-Syndrome.