The regulatory agency is reviewing Reata’s application of bardoxolone to treat patients with chronic kidney disease caused by Alport syndrome, a rare genetic disease.
The FDA’s Cardiovascular and Renal Drugs Advisory Committee has advised against approval of Reata Pharmaceuticals’ bardoxolone methyl for the treatment of patients with chronic kidney disease (CKD) caused by Alport syndrome. The committee indicated that the provided evidence does not demonstrate that bardoxolone is effective in slowing the progression of CKD and that its benefits outweigh its risks.
“We are disappointed with the outcome of the committee’s vote regarding bardoxolone, an investigational drug with a novel mechanism of action,” Warren Huff, Reata’s president and chief executive officer, said in a statement. “We believe the scientific evidence supports bardoxolone approval in the U.S. 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.”
Reata officials said they will continue to work closely with the agency to provide additional information and data until the upcoming Prescription Drug User-Fee Act date of Feb. 25, 2022.
The company’s application was accepted by the FDA in April 2021. The submission was based on the phase 3 CARDINAL trial that found that improvement in kidney function as measured by estimated glomerular filtration rate (eGFR) at week 100 and week 104, compared with patients treated with placebo. EGFR is an estimate of how well the kidney’s function and is considered a reliable test by doctors.
Bardoxolone was generally reported to be well tolerated in this study, and the safety profile was similar to that observed in prior trials.
In materials released ahead of the committee meeting, the FDA indicated that bardoxolone may only provide a one-time benefit shortly after initiating treatment and does not grow over time. “The 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,” regulatory officials said.
Alport syndrome is a rare, genetic form of CKD caused by mutations in the genes encoding type IV collagen, which is a major structural component of the glomerular basement membrane in the kidney. Alport syndrome affects both children and adults. The kidneys of patients with Alport syndrome progressively lose the capacity to filter waste products out of the blood, which can lead to end-stage kidney disease and the need for chronic dialysis treatment or a kidney transplant. In patients with the most severe forms of the disease, approximately 50% progress to dialysis by age 25, 90% by age 40, and nearly 100% by age 60. According to the Alport Syndrome Foundation, Alport syndrome affects about 30,000 to 60,000 people in the United States.
There are currently no therapies approved to treat CKD caused by Alport syndrome.