Nurandociguat shows preliminary efficacy in patients with CKD

Nurandociguat, a soluble guanylate cyclase (sGC) activator, significantly improved urinary albumin-to-creatinine ratio (UACR) after 16 weeks of treatment compared with placebo, while increasing the incidence of hypotension and syncope.

Prof. Christoph Wanner (University Hospital of Würzburg, Germany) presented data from ALPINE 1 (NCT06522997), a phase 2b, prospective, randomised, controlled trial evaluating multiple dose levels of nurandociguat compared to placebo in patients with chronic kidney disease (CKD) [1]. Participants were eligible if they had an estimated glomerular filtration rate (eGFR) between 20 and 75 mL/min/1.73 m², a UACR between 200 and 3500 mg/g, and were receiving the maximally tolerated labelled dose of standard-of-care therapy, including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) plus sodium-glucose cotransporter 2 (SGLT2) inhibitors, finerenone, or glucagon-like peptide-1 receptor (GLP-1R) agonists. Patients with a systolic blood pressure of <100 mmHg or clinically relevant hypotension were excluded. The primary endpoint was the mean change in UACR at week 16. Overall, 751 patients were included.

A statistically significant reduction in UACR was observed with every nurandociguat dose compared with placebo (P<0.05). However, the minimum dose required to achieve a 30% improvement in UACR compared with placebo could not be determined. Treatment-emergent adverse events of special interest occurred more commonly with nurandociguat, including syncope, symptomatic hypotension, and worsening kidney function, with event rates increasing at higher dose levels.

“The study met its primary efficacy endpoint, demonstrating a statistically significant dose-response relationship,” concluded Prof. Wanner. “A statistically significant reduction in UACR was observed through week 16 across all dose groups. Nurandociguat was generally well tolerated, with a dose-dependent increase in treatment-related adverse events.”

Wanner C, et al. Effect of nurandociguat on albuminuria in patients with CKD: A phase 2, randomized dose-finding clinical trial. ERA 2026, 3–6 June. Glasgow, Scotland.