Dapagliflozin-Zibotentan Combination Therapy Advances to Phase 3 Trial with 52.5% Reduction in CKD Biomarker

▎WuXi

Edited by Kant Content Team

AstraZeneca today announced that after 12 weeks of combination treatment with zibotentan and dapagliflozin, compared to dapagliflozin monotherapy, there was a statistically significant and clinically relevant reduction in the urine albumin-to-creatinine ratio (UACR) in patients with chronic kidney disease (CKD). UACR is a diagnostic marker of albuminuria.

In the Phase 2b ZENITH-CKD trial, patients receiving the combination therapy showed significant improvement in UACR at 12 weeks compared to those receiving dapagliflozin monotherapy.Patients receiving the higher dose of zibotentan (1.5 mg) and dapagliflozin (10 mg) combination therapy experienced a –33.7% reduction in UACR (90% CI: –42.5 to –23.5; p

, while patients receiving the lower dose (0.25mg zibotentan/ 10 mg dapagliflozin) combination therapy showed a UACR reduction of –27.0% (90% CI: –38.4 to –13.6; p=0.002). Moreover, compared with baseline, the mean percentage decrease in UACR was –52.5% (90% CI: –59.0 to –44.9) in the higher-dose combination therapy group and –47.7% (90% CI: –55.7 to –38.2) in the lower-dose therapy group.

These data were presented at the American Society of Nephrology (ASN) Kidney Week 2023 and simultaneously published in the prestigious medical journal, The Lancet.The data supports the advancement of the combination therapy to Phase 3 trials, which are planned to begin in the fourth quarter of 2023.

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Zibotentan is a selective endothelin A (ETA) receptor antagonist., exerts therapeutic effects by enhancing renal blood flow, reducing albuminuria, and alleviating vascular stiffness.Dapagliflozin, an SGLT2 inhibitor, has been shown to slow disease progression in high-risk CKD patients.This drug works by promoting the excretion of fluid from the extravascular space, which may help reduce the risk of fluid retention.