The FDA said that the shared NDA documents did not show ample proof that bardoxolone methyl effectively slows down kidney function loss in patients with Alport syndrome.
FDA didn’t approve Reata Pharmaceutical’s new NDA for Alport syndrome.
The U.S. Food and Drug Administration has rejected Reata Pharmaceuticals’ New Drug Application for its proposed chronic kidney disease drug, citing a lack of proof of effectiveness.
In its Complete Response Letter (CRL), the FDA said the documents submitted to support the NDA did not show ample proof that bardoxolone methyl (bardoxolone) is effective in slowing down kidney function loss in patients diagnosed with Alport syndrome. It reportedly does not clearly demonstrate the ability to reduce the risk of progression to kidney failure. Reata submitted its NDA in February 2021 for patients aged 12 years and older.
The decision is based on safety and efficacy concerns raised at the Cardiovascular and Renal Drugs Advisory Committee meeting on December 8, 2021. The regulator has asked Reata to produce additional data to carry its NDA application through to success, particularly those that show whether bardoxolone has a clinically relevant effect on the QT interval and determine if its benefits significantly outweigh the risks.
What Did FDA Say About Reata’s Alport Syndrome Drug NDA?
“FDA review team does not believe the submitted data demonstrate that bardoxolone is effective in slowing the loss of kidney function in patients with AS and reducing the risk of progression to kidney failure. In addition to the concerns with CARDINAL Phase III, there are no data in this application from an animal model of Alport syndrome or other adequate and well-controlled clinical trials in AS or CKD that show that bardoxolone slows the loss of kidney function,” the FDA said in its briefing.
In a statement, Reata acknowledged the FDA’s decision and said it will work closely with the regulator to bring the drug to more patients in the U.S. as soon as possible.
“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. We will continue to work with the FDA to confirm our next steps on our Alport syndrome program,” noted Warren Huff, the chief executive officer of Reata Pharmaceuticals.
Bardoxolone is an investigational, once-daily, orally administered Nrf2 activator. Nrf2 is a transcription factor that induces pathways to resolve inflammations by reviving cell function. It already has an Orphan Drug designation from the FDA and the European Commission for autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome.
Reata has also submitted a Marketing Authorization Application to the European Medicines Agency for CKD from Alport syndrome, which is still under review. At the same time, its Japan partner Kyowa Kirin sent an NDA to the Japanese Ministry of Health, Labor and Welfare, which is also under review.
Alport syndrome is a rare type of chronic kidney disease caused by mutations in the genes that encode type IV collagen, a key component of kidney function. The illness affects both children and adults, starting with the decreased capacity to filter waste from the blood and later leading to end-stage renal disease requiring dialysis or kidney transplant. In severe cases, around 50% of patients need to undergo dialysis by 25 years old, 90% by 40 years old and 100% by 60. There are currently no treatments for this illness.
Bardoxolone is currently being studied in the FALCON Phase III and the AYAME Phase III studies in the U.S. and Japan, respectively.
