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Bardoxolone tested in phase 3 trials for Alport Syndrome, other CKD-related diseases
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BOSTON — Reata Pharmaceuticals presented details and a status report from its CARDINAL trial at the CKD3 Summit here showing how bardoxolone is being tested to treat patients with Alport Syndrome. Separately, evaluation of the drug to treat four other forms of rare chronic kidney diseases, all with different underlying pathologies, is showing positive results in company trials.
“For many years, we identified the typical profile of Alport Syndrome as only including individuals (classically young males) with hearing loss, eye abnormalities, and progressive kidney disease,” Geoffrey Block, MD, Reata’s vice president for nephrology, told Healio/Nephrology. “But now with more widely available gene sequencing, … we are learning that the genetic abnormalities which define Alport Syndrome do not just affect young males; experts now recognize that there are many people previously identified as ‘carriers’ or with ‘benign familial hematuria’ or ‘thin basement membrane disease’ with the same genetic abnormalities that have CKD and are at risk for ESKD.”
The testing of bardoxolone for other CKD-related diseases has been completed in a phase 2 trial called PHOENIX which included 103 patients with autosomal dominant polycystic kidney disease, CKD associated with type 1 diabetes (T1D), IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS).
Alport Syndrome is the second most common inherited cause of kidney failure after ADPKD and affects as many as 60,000 people in the United States. It is caused by a genetic defect in type IV collagen, a component in building the glomerular basement membrane. Bardoxolone methyl affects the underlying pathologic processes associated with mitochondrial dysfunction, inflammation and oxidative stress, a company press release said.
CARDINAL is an international, multicenter, phase 2/3 study. The phase 2 portion of CARDINAL is open-label and enrolled 30 patients. The phase 3 portion of CARDINAL is double-blind, placebo-controlled, and has 157 patients enrolled randomized on a 1:1 basis to once-daily, oral bardoxolone methyl or placebo. A dose-titration scheme is being used to reach a goal dose of 20 mg or 30 mg. All patients in the study will have the same visit and assessment schedule and will be followed for 2 years.
Key eligibility criteria for the phase 3 CARDINAL trial included patients aged 12 to 70 years old with a confirmed genetic or histological diagnosis of Alport Syndrome and baseline eGFR values between 30 mL/min/1.73 m2 to 90 mL/min/1.73 m2.
While the phase 2 primary efficacy endpoint in the trial was the change from baseline in eGFR after 12 weeks of treatment, the phase 3 primary endpoint is the on-treatment eGFR change from baseline in bardoxolone methyl-treated patients compared to placebo at weeks 48 and 100. A key secondary endpoint is the change in eGFR 4 weeks post-treatment (weeks 52 and 104) in an effort to demonstrate that bardoxolone methyl has disease-modifying activity.
In addition to Reata’s ongoing bardoxolone programs in the United States, the drug is being evaluated for patients with diabetic kidney disease by Kyowa Hakko Kirin, which has development rights in Japan and other selected Asian markets. –by Mark E. Neumann
Reference:
https://reatapharma.com/our-science/pipeline/ongoing-research/iga-nephropathy-igan/