Efficacy and safety of avenciguat in diabetic and non-diabetic kidney disease: Pooled analysis from two Phase II randomised controlled clinical trials

sGc is important for proper endothelial function in vascular beds. Avenciguat (BI 685509) is a novel, potent sGc activator in development for treatment of CKD. Two trials investigated the efficacy and safety of avenciguat in patients with diabetic (NCT04750577) or non-diabetic (NCT04736628) CKD.

In these two Phase II double-blind, placebo-controlled trials of identical design, adults aged ≥18 years with CKD (eGFR ≥20–<90 mL/min/1.73 m², UACR ≥200–<3500 mg/g) were randomised to receive 20 weeks of placebo or avenciguat 1, 2 or 3 mg TID (including a 4-week up-titration period) as adjunct to maximum tolerated ACE inhibitor or ARB. The primary endpoint was change from baseline in UACR in 10-hour urine at Week 20. Safety was monitored throughout both trials. At trial completion, individual patient data were pooled and analysed according to a pre-specified analysis plan.

A total of 500 patients were randomised and received placebo (n=122) or avenciguat 1 mg (n=125),2 mg (n=126) or 3 mg (n=127) TID. Avenciguat reduced UACR in 10-hour urine compared with placebo throughout the treatment period. At Week 20, the placebo-corrected geometric mean percent changes (95% CI) from baseline in UACR in 10-hour urine with avenciguat 1, 2 and 3 mg TID were −15.5% (−26.4, −3.0), −13.2% (−24.6, −0.1) and −21.5% (−31.7, −9.8), respectively. Avenciguat was well tolerated. Hypotension was reported in 33 patients (8.7%) treated with any avenciguat dose and 3 patients (2.5%) receiving placebo.

Avenciguat was effective in lowering albuminuria and was well tolerated in patients with diabetic and non-diabetic CKD.