Novel VAP-1 inhibitor shows promise for diabetic kidney disease
medwireNews: The novel, orally active vascular adhesion protein (VAP)-1 inhibitor ASP8232 effectively reduces albuminuria, with few side effects, in patients with type 2 diabetes and chronic kidney disease, phase II study data show.
After 12 weeks of daily treatment with ASP8232 40 mg, 60 patients randomly assigned to receive the study drug had a mean 17.7% reduction in first morning void urinary albumin-to-creatinine ratio (UACR).
By comparison, the 60 patients randomly assigned to receive placebo for 12 weeks had a mean 2.3% rise in UACR versus baseline, giving a significant placebo-adjusted difference of 19.5% between the two groups.
All of the patients included in the ALBUM trial were also receiving treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which Kamyar Kalantar-Zadeh (University of California Irvine Medical Center, Orange, USA) and co-authors of a comment that accompanies the study in The Lancet Diabetes & Endocrinology say allows “an additive treatment effect to be confirmed.”
The effect of ASP8232 on UACR was greatest at 12 weeks, but was still apparent to a smaller degree up to 24 weeks after treatment discontinuation.
The reduction in 24-hour albuminuria from baseline to week 12 was larger, although not significantly so, in the ASP8232 group than in the placebo group (26.7 vs 8.4%), and more participants who received ASP8232 had a clinically relevant (≥30%) reduction in first morning void UACR (37 vs 22%).
However, patients receiving ASP8232 experienced a small decline in estimated glomerular filtration rate compared with placebo, which was present from weeks 2 to 12, but resolved during the additional 24-week follow-up period.
Dick de Zeeuw (University Medical Center Groningen, the Netherlands) and co-investigators found that patients in the ASP8232 group tolerated the treatment well and had a similar rate of treatment-emergent adverse events to the placebo group (61 vs 56%). There were no drug-related serious adverse events, but one severe case of dry mouth was possibly related to ASP8232.
De Zeeuw and co-authors conclude that the ALBUM study “provides the first clinical evidence that VAP-1 activity is involved in the pathophysiology of human diabetic kidney disease and that VAP-1 inhibition could improve disease status.”
They add: “Owing to its novel mechanism, ASP8232 might have the potential to provide clinical benefit to patients with type 2 diabetes and chronic kidney disease when used in conjunction with the current standard of care.”
And Kalantar-Zadeh et al agree. They write: “Although further studies are needed to assess the efficacy and safety of this innovative therapy in patients with diabetic kidney disease when added to standard interventions, the findings of this study are a cause for cautious optimism that targeting this novel pathway might provide meaningful renal and cardiac benefits that [complement] currently available therapies for chronic kidney disease.”
By Laura Cowen
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