EU Grants Bardoxolone Orphan Drug Status as Potential Alport Therapy, Phase 3 Trial Enrolling

The European Commission (EC) has granted orphan drug status to bardoxolone methyl (bardoxolone)as a possible treatment for Alport syndrome, the therapy’s developer, Reata Pharmaceuticals, announced.

Its effectiveness and safety are now being evaluated in a global clinical trial that’s enrolling patients with confirmed Alport syndrome and symptoms of kidney disease.

The EC’s decision was based on the positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). The

Orphan drug status in the EU aims to encourage therapies for rare and serious diseases, through a series of benefits, including 10 years of market exclusivity once the therapy is approved, and reduction on fees. Additionally, it provides assistance in designing protocols assistance and gives access to the centralized authorization procedures.

“Orphan designation in the European Union is an important milestone for the Company and for Alport syndrome patients.  There are currently no approved treatments for Alport syndrome, and we hope to demonstrate that bardoxolone can serve as a safe and effective treatment option for these patients,” Warren Huff, Reata’s chief executive officer, said in a press release.

Bardoxolone methyl is a small molecule drug aimed at reducing oxidative stress and inflammation, which may improve kidney function in Alport patients. The investigative therapy binds to a protein called KEAP1, preventing it from degrading the Nrf2 protein so as to promote the healthy functioning of mitochondria — a cell’s energy source or powerhouse.

The increased activation of Nrf2 stimulates the production of anti-oxidant proteins, reducing the oxidative stress and damage to proteins and improve mitochondrial energy production.

Bardoxolone is currently being studied in CARDINAL, a Phase 2/3 study for the treatment of Alport syndrome (NCT03019185). The trial — taking place at 68 sites across the United States, Europe, Canada, Australia and Japan — is currently enrolling eligible patients, ages 12 to 60.

The Phase 2 part of the trial was a dose-escalating study in 30 people. Patients were initially treated with 5 mg of oral bardoxolone once daily, followed by an escalation to 10 mg at week two and up to 20 mg at week four. Those with urine albumin-to-creatinine ratio levels above 300 mg/g received 30 mg at week six.

Interim data collected after 12 weeks of treatment showed that the investigative treatment can promote clinically meaningful improvements in kidney function in these patients.

The Phase 3 part will continue to evaluate the potential effectiveness and safety of bardoxolone methyl in a double-blind, randomized, placebo-controlled study. Reata is now recruiting participants for this part, which is expected to include up to 180 participants at the 68 sites. More information is available here.