Early phase data show albuminuria improvement with avenciguat

The soluble guanylyl cyclase activator avenciguat improved albuminuria and slightly increased hypotension in participants with chronic kidney disease (CKD) according to early phase pooled data from a phase 1b and phase 2 trial.

Data were pooled from a phase 1b trial with participants with diabetic CKD (NCT03165227) [1] and a phase 2 trial with non-diabetic CKD (NCT04736628). Inclusion criteria were an eGFR between ≥20 and <90 mL/min/1.73 m², a urine albumin-creatinine ratio between ≥200 and <3500 mg/g and receiving a maximally tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. 500 participants were randomised (1:3) to avenciguat (1, 2, or 3 mg 3 times daily) or a corresponding placebo. The primary endpoint of the pooled analysis was the 10-hour urine albumin-creatinine ratio at week 20 [2].

Avenciguat reduced the 10-hour urine albumin-creatinine ratio at week 20 irrespective of the regimen dose. Corrected by placebo values, avenciguat reduced the 10-hour urine-albumin-creatinine ratio by a geometric mean of -15.5% (95% CI -26.4 to -3.0; P=0.02), -13.2% (95% CI -24.6 to -0.1; P=0.0479) and -21.5% (95% CI -31.7 to -9.8; P<0.001) for the 1, 2, and 3 mg dose regimens, respectively, with no difference between participants with or without diabetes. Furthermore, 39.7%, 37.7% and 48.3% of participants receiving avenciguat 1, 2, and 3 mg achieved ≥20% reduction from baseline in urine albumin-creatinine ratio at week 20, compared with 22.9% with placebo. Hypotension was reported more commonly with avenciguat (5.6%–9.5%) versus placebo (2.5%) and discontinuations due to adverse events were more common in the avenciguat arm (4.0%–8.7% vs 3.3%). However, serious adverse events and adverse events of special interest tended to be similar between the avenciguat and placebo groups.

“Avenciguat was effective in reducing albuminuria in participants with diabetic and non-diabetic CKD with the highest effect seen with the 3 mg dose regimen”, concluded Prof. Hiddo J.L. Heerspink (University Medical Center Groningen, The Netherlands). These results support avenciguat dose selection in future trials.

 

1. Cherney DZI, et al. Diabetes Obes Metab. 2023;25(8):2218–2226.
2. Heerspink HJL, et al. Efficacy and safety of avenciguat in diabetic and non-diabetic kidney disease: Pooled analysis from two Phase II randomised controlled clinical trials. Abstract #79, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024