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American Society of Nephrology (ASN)’s Kidney Week 2023 | News | Updates | iPharmaCenter

November 03, 2023

AstraZeneca's Zibotentan/Dapagliflozin Combination Shows Significant Benefits in Chronic Kidney Disease Patients

AstraZeneca has announced findings from the ZENITH-CKD Phase IIb trial, revealing the effectiveness of the zibotentan/dapagliflozin combination in patients diagnosed with chronic kidney disease (CKD).

The ZENITH-CKD trial, a Phase 2 double-blind study, aimed to assess the efficacy of the zibotentan/dapagliflozin combination in comparison to dapagliflozin monotherapy. This evaluation involved two zibotentan/dapagliflozin combination doses: zibotentan 1.5 mg plus dapagliflozin and zibotentan 0.25 mg plus dapagliflozin.

After 12 weeks of treatment, the high-dose combination revealed a reduction in UACR (urinary albumin-to-creatinine ratio) of -33.7% compared to monotherapy, and the low-dose combination displayed a reduction of -27.0%. Specifically, the high-dose combination resulted in a change in baseline UACR of -52.5%, while the low-dose combination showed a change of -47.7%.

Zibotentan, an endothelin A receptor inhibitor, is associated with fluid retention and contributes to reducing albuminuria, while dapagliflozin focuses on diminishing the progression of chronic kidney disease (CKD).


November 03, 2023

Boehringer Ingelheim's Aldosterone Synthase Inhibitor Combined with Empagliflozin Shows Promising Results in Chronic Kidney Disease Patients

Boehringer Ingelheim's Phase 2 data announcement showcased promising results regarding the combination of BI 690517, a selective aldosterone synthase inhibitor, and empagliflozin, an SGLT2 inhibitor, in patients with chronic kidney disease.

The administration of BI 690517 alongside empagliflozin demonstrated a reduction in albuminuria by 39.5% compared to the placebo.

A crucial secondary endpoint, the urinary albumin-to-creatinine ratio (UACR), was significantly reduced by 70% through this combination. The trial initially involved administering patients with empagliflozin 10 mg for eight weeks, followed by the evaluation of three doses of BI 690517 (3 mg, 10 mg, and 20 mg) for 14 weeks. Comparing the placebo-corrected UACR reduction in the patient population showed the following outcomes:

  • 3 mg: -9.4%

  • 10 mg: -39.5%

  • 20 mg: -33.2%

BI 690517 works by inhibiting aldosterone synthase, a critical enzyme involved in aldosterone synthesis. Elevated levels of aldosterone are associated with conditions such as hypertension, chronic kidney disease, and heart failure.

Boehringer Ingelheim further announced its plans to launch the EASi-KIDNEY trial in 2024, aiming to recruit 11,000 patients with chronic kidney disease.


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