|Reata Announces Initiation of Phase 2/3 Study of Bardoxolone Methyl in the Treatment of Chronic Kidney Disease Due to Alport Syndrome|
The Alport Syndrome Foundation’s Executive Director
"Based on our extensive clinical experience with bardoxolone methyl in patients with diabetic CKD, as well as in our ongoing Phase 2 and Phase 3 trials for bardoxolone in other orphan diseases, we hope to demonstrate that bardoxolone methyl can serve as a meaningful new treatment option for patients with Alport syndrome," said
Overview of Clinical Trial Program in Alport Syndrome
The Phase 2 portion of the study is open-label and will enroll up to 30 patients from 12 to 60 years old with estimated glomerular filtration rates (eGFR) between 30 to 90 mL/min/1.73 m2. Fifteen patients with microalbuminuria will receive up to 20 mg of bard once daily, and 15 patients with macroalbuminuria will receive up to 30 mg of bard once daily. The primary endpoint for the Phase 2 portion of the study is change in eGFR at week 12 compared to baseline.
The Phase 3 portion is designed to support regulatory approval of bard. This portion will be double-blind and placebo-controlled and will randomize approximately 180 patients on a 1:1 basis to once-daily, oral bard or placebo. Similar to the Phase 2 portion of the trial, the study will assess dose escalation of bard from 5 mg to a maximum daily dose of 20 mg or 30 mg based on baseline proteinuria at randomization. The primary efficacy endpoint is the on-treatment change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo after 48 weeks. The key secondary endpoints will be the change from baseline in eGFR following a 4-week withdrawal of drug after one and two years of treatment. Based on
About Alport Syndrome
Alport syndrome is a rare, genetic disease caused by mutations in the genes encoding type IV collagen, a major structural component of the glomerular basement membrane (“GBM”) in the kidney. The abnormal expression of type IV collagen causes loss of GBM integrity, abnormal leakage of proteins such as albumin through the GBM, and excessive reabsorption of protein in the proximal tubules of the kidney. Like other forms of CKD, excessive reabsorption of protein in the tubules induces oxidative stress, chronic inflammation, and renal interstitial inflammation and fibrosis.
Alport syndrome affects approximately 12,000 people in
About Bardoxolone Methyl
Bardoxolone methyl is an experimental, oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling. Bardoxolone methyl is currently being studied in CATALYST, a Phase 3 study for the treatment of connective tissue disease associated pulmonary arterial hypertension (CTD-PAH).
This press release includes certain disclosures which contain “forward-looking statements,” including, without limitation, statements regarding the success, cost and timing of our product development activities and clinical trials, our plans to research, develop and commercialize our product candidates, our ability to obtain and retain regulatory approval of our product candidates, estimates of our expenses and our needs for additional financing, and our ability to obtain additional financing for our product development activities and existing and future clinical trials and pre-clinical programs. You can identify forward-looking statements because they contain words such as “believes,” “will,” “may,” “aims,” “plans” and “expects.” Forward-looking statements are based on Reata’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in Reata’s filings with the
1 Rheault M, Gross O, Appel G, et al. Change in glomerular filtration rate and renal biomarkers in patients with chronic kidney disease due to Alport syndrome: interim results from the ATHENA study, a prospectively designed natural history study. Nephrol Dial Transplant 2016;31:i126.
2 Jais J, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 2000;11:649-57.
3 Zoja C, Corna D, Locatelli M, et al. Targeting Keap1-Nrf2 Pathway Ameliorates Renal Inflammation and Fibrosis in Mice with Protein-Overload Proteinuria.
4 Aminzadeh MA,
5 Camer D, Yu Y, Szabo A, et al. Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fed diet. Chem Biol Interact 2016;243:10-18.