공고 • Nov 10
Reata Pharmaceuticals, Inc. Announces Positive Results From Year 2 of the Pivotal Phase 3 CARDINAL Study of Bardoxolone Methyl in Patients with Alport Syndrome
Reata Pharmaceuticals, Inc. announced that the Phase 3 CARDINAL study of bardoxolone methyl in patients with chronic kidney disease caused by Alport syndrome met its primary and key secondary endpoints at the end of Year 2. At Week 100, in the intent-to-treat population, which included estimated glomerular filtration rate values for patients who either remained on or discontinued study drug, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR of 7.7 mL/min/1.73 m2 (p=0.0005). In the modified ITT analysis, which assessed the effect of receiving treatment by excluding values after patients discontinued treatment, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR at Week 100 of 11.3 mL/min/1.73 m2 (p<0.0001). At Week 104 (four weeks after last dose in second year of treatment), patients in the ITT population treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR of 4.3 mL/min/1.73 m2 (p=0.023). Bardoxolone treatment was generally reported to be well-tolerated. In the long-term extension study, for the 14 patients who completed three years of treatment, bardoxolone treatment resulted in a mean increase from baseline in eGFR of 11.0 mL/min/1.73 m2. Based on these positive results and following a recently completed pre-NDA meeting with the U.S. Food and Drug Administration, it plan to proceed with the submission of an NDA for full marketing approval in the United States in the first quarter of 2021. It also plan to pursue marketing approval outside of the United States and work has commenced on preparations to file for marketing approval in Europe. The Phase 3 CARDINAL study was an international, multi-center, double-blind, placebo-controlled, randomized clinical trial that enrolled 157 patients with Alport syndrome at approximately 50 study sites in the United States, Europe, Japan, and Australia. Patients were randomized 1:1 to bardoxolone or placebo. The primary endpoint for Year 2 of the study was the change from baseline in eGFR after 100 weeks of treatment (end-of-treatment). The key secondary endpoint for Year 2 of the study was the change from baseline in eGFR at Week 104 (four weeks after last dose in second year of treatment). At Week 100, in the ITT population, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR of 7.7 mL/min/1.73 m2 (p=0.0005). Patients treated with bardoxolone experienced a mean change from baseline in eGFR of -0.8 mL/min/1.73 m2, while patients treated with placebo experienced a mean change from baseline in eGFR of -8.5 mL/min/1.73 m2. In the mITT analysis, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR at Week 100 of 11.3 mL/min/1.73 m2 (p<0.0001). Patients treated with bardoxolone experienced a mean increase from baseline in eGFR of 1.7 mL/min/1.73 m2, while patients treated with placebo experienced a mean decline from baseline in eGFR of -9.6 mL/min/1.73 m2. At Week 104 (four weeks after last dose in second year of treatment), patients in the ITT population treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR of 4.3 mL/min/1.73 m2 (p=0.023). Patients treated with bardoxolone experienced a mean change from baseline in eGFR of -4.5 mL/min/1.73 m2, while patients treated with placebo experienced a mean change from baseline in eGFR of -8.8 mL/min/1.73 m2. Efficacy was observed across multiple subgroups at Week 100 and Week 104, including pediatric patients and patients with different genetic subtypes of Alport syndrome. The largest treatment effect at Week 104 was observed in the pediatric subgroup where the difference between treatment groups was 14.6 mL/min/1.73 m2 (p=0.004). The risk of kidney failure events (defined as end stage kidney disease, confirmed 30% eGFR decline, or confirmed eGFR < 15 mL/min/1.73 m2) was reduced by approximately 50% in bardoxolone-treated patients (9 patients versus 17 patients in placebo). Bardoxolone was generally reported to be well tolerated in this study, and the safety profile was similar to that observed in prior trials. Seventy-five patients (97%) receiving bardoxolone and 77 patients (96%) receiving placebo experienced an adverse event (“AE”). Ten patients (13%) receiving bardoxolone and four patients (5%) receiving placebo discontinued study drug due to an AE, and no individual AE contributed to more than two discontinuations in either group. The reported AEs were generally mild to moderate in intensity, and the most common AEs observed more frequently in patients treated with bardoxolone compared to patients treated with placebo were muscle spasms and increases in aminotransferases. Eight patients (10%) receiving bardoxolone and 15 patients (19%) receiving placebo experienced a treatment-emergent serious adverse event. No SAEs were reported in pediatric patients treated with bardoxolone. No fluid overload or major adverse cardiac events were reported in patients treated with bardoxolone. Blood pressure was not significantly different between the two groups. The urinary albumin-to-creatinine ratio was not significantly different between treatment groups at Week 100 or Week 104. Non-kidney symptoms associated with Alport syndrome, including psychiatric, hearing, vestibular, and ocular AEs, occurred less frequently in bardoxolone-treated patients.
