Verinurad with febuxostat significantly reduces albuminuria and hyperuricaemia in patients with type 2 diabetes

The results of a phase IIa clinical trial presented today at the Annual European Congress of Rheumatology (EULAR 2019) demonstrate a rapid reduction in albuminuria and hyperuricaemia in patients with type II diabetes with combined treatment of verinurad and febuxostat.

The primary endpoint of the study was met; results reveal a 39% reduction in urinary albumin-to-creatinine ratio (UACR) after 12 weeks with combined treatment of verinurad 9mg and febuxostat 80mg versus placebo (p=0.07). The study also shows a 57% reduction in serum urate (sUA) in the treatment group versus a 7% increase in the placebo group (p<0.0001) at 12 weeks. This effect was sustained at 24 weeks with a 62% reduction versus a 5% increase (p<0.0001). The effect on sUA was likely underestimated due to sample collection scheduling. The study also measured estimated glomerular filtration rate (eGFR) but the changes were insignificant.

"Although these are early clinical findings in a limited group of patients, our results show that combined treatment with verinurad and febuxostat in patients with diabetes results in a rapid reduction in hyperuricaemia and albuminuria sustained through week 24," said Robert Terkeltaub, MD, Professor of Medicine, University of California San Diego, USA. "Further studies are planned to confirm the efficacy of urate lowering strategies combining verinurad and xanthine oxidase inhibitors in slowing progression of chronic kidney disease."

Verinurad is an inhibitor of the uric acid transporter (URAT1) and is currently under investigation for the treatment of hyperuricaemia and kidney disease. Febuxostat is a potent, selective xanthine oxidase inhibitor used to lower urate levels in patients with gout and hyperuricaemia. It is recommended in patients who do not reach target on, or are intolerant to, allopurinol. It is often used in patients with renal impairment since it is primarily metabolised in the liver.

"We welcome these positive results and look forward to the future clinical development of this novel urate-lowering treatment strategy, particularly in patients with hyperuricaemia and kidney disease," said Professor Hans Bijlsma, President, EULAR.

The trial included 60 patients with type II diabetes who had a sUA of 6.0mg/dL or above, eGFR of 30mL/min/1.73m2 or above, and UACR of 30-3500 mg/g. Patients were randomised to receive either verinurad 9mg and febuxostat 80mg (treatment group) or placebo. Patients were excluded if they had a history of gout or recent treatment with urate-lowering therapy which avoided the need to administer gout prophylaxis. Most adverse events were mild to moderate, those reported in more than one patient in the treatment group were diarrhoea, dizziness and nasopharyngitis, and only one gout flare-up was reported (in the treatment group).