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Isuzinaxib effective in patients with CKD and T2D

ASN 2022
Phase 2
Isuzinaxib was shown to be effective on major kidney-function markers such as urine albumin-to-creatinine ratio (UACR) and kidney injury molecule-1, particularly in patients with low kidney function. No clinically relevant safety findings were observed with isuzinaxib [1].

Isuzinaxib (APX-115) is a potent and novel small-molecule inhibitor of NADPH-oxidases, enzymes that mediate production of reactive oxygen species, causing increased oxidative metabolism leading to inflammatory responses and profibrotic factors. Reactive oxygen species trigger kidney cells to secrete cytokines, potentiating the activation of macrophages, which also contribute to diabetic kidney disease (DKD). Isuzinaxib was developed for the treatment of DKD.

In a randomised, placebo-controlled, double-blind, phase 2 trial (NCT04534439), 140 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) were randomised to isuzinaxib 400 mg orally or placebo for 12 weeks. Eligibility criteria were: age 18–80 years, clinical diagnosis of T2D and nephropathy, urinary albumin concentration 200–3,000 mg/g, estimated glomerular filtration rate (eGFR) 30–90 mL/min/1.73m2, haemoglobin A1c ≤10, stable treatment ≥3 months with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and stable antihyperglycaemic treatment ≥3 months. The primary endpoint was mean change in UACR at week 12. Secondary endpoints included safety and tolerability, eGFR change, and biomarker assessment. At week 12, mean change in UACR in patients in the isuzinaxib group was −21% versus 2.5% in the placebo group (95% CI 3.8–398.1; P=0.046). This translates into a 19% difference compared to placebo which was not significant. However, patients with eGFR <45 mL/min/1.73m2 who received isuzinaxib showed a significant UACR reduction compared with placebo which translated into a 47% difference (P=0.0197). There was no difference in mean change in eGFR at week 12 between the 2 groups. Furthermore, no clinically relevant findings were observed regarding clinical examination, biological vital signs, laboratory findings, or ECG parameters that could suggest any significant safety issues associated with isuzinaxib. Despite the relatively small number of patients in the study, the trial demonstrated the first clinical evidence of isuzinaxib effectiveness in DKD. Future clinical developments will likely focus on patients with advanced CKD and a longer treatment period.

  1. Cha DR, et al. Effect of Isuzinaxib, Pan NOX Inhibitor in Patients With Type 2 Diabetes and CKD in a Randomized, Double Blind, Placebo Controlled Phase 2 Trial. FR-OR62, ASN Kidney Week 2022,
    3–6 Nov.


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