Reata’s Bardoxolone for Alport Syndrome Granted FDA Orphan Drug Status

Bardoxolone methyl, an investigational treatment for kidney damage associated with Alport syndrome, has been granted orphan drug status by the U.S. Food and Drug Administration (FDA), Reata Pharmaceuticals announced.

Bardoxolone methyl (bardoxolone) is an oral, once-daily therapy that is being evaluated in the CARDINAL Phase 2/3 clinical trial (NCT03019185) in patients with chronic kidney disease (CKD) triggered by Alport syndrome.

The trial aims to determine whether bardoxolone improves kidney function similar to that observed in patients with other forms of CKD. The trial started in January 2017 and is still recruiting patients across the U.S.; results from the Phase 2 portion are expected by year’s end.

The FDA’s orphan drug designation is applied to therapies for the treatment, diagnosis, or prevention of diseases affecting fewer than 200,000 people in the United States. Orphan status is a crucial step in drug development and will provide Reata with incentives such as tax credits for clinical testing, seven years of market exclusivity, and exemption from a prescription drug user fee.

“This orphan designation is an important milestone for the company and for Alport syndrome patients,” Warren Huff, Reata’s president and CEO, said in a press release. “There are currently no FDA-approved treatments for Alport syndrome, and we hope to demonstrate that bardoxolone can serve as a safe and effective treatment option for these patients.”

Reata is also conducting the CATALYST Phase 3 study (NCT02657356) to evaluate bardoxolone in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease. This study, too, is recruiting patients.

Bardoxolone activates Nrf2, a transcription factor (proteins that control the conversion of DNA into RNA). Nrf2 promotes molecular pathways that normalize the function of mitochondria, the cellular organelles responsible for respiration and energy production, decrease oxidative stress, and inhibit pro-inflammatory mechanisms.

Alport syndrome is a rare genetic condition characterized by progressive kidney failure that ultimately results in chronic kidney disease (CKD). About 50 percent of male patients with Alport syndrome need dialysis or a kidney transplant by age 25.

The disorder is induced by mutations in the genes of type IV collagen, a key structural component of the glomerular basement membrane, a component of the kidney’s filtration barrier. The altered production of type IV collagen disrupts membrane integrity and causes abnormal leakage of proteins. Excessive protein reabsorption is observed in the proximal tubules of the kidney, which, as in other forms of CKD, induces oxidative stress, chronic inflammation, and fibrosis.