Tolvaptan Cleared in US for ADPKD in Adults
For the first time, the FDA has approved a pharmaceutical treatment for rapidly progressing autosomal dominant polycystic kidney disease in adults.
Tolvaptan has received FDA marketing clearance as a treatment for rapidly progressing autosomal dominant polycystic kidney disease (ADPKD) in adults. It is the first FDA-approved drug for this indication.
The drug, which is being marketed as Jynarque by Otsuka Pharmaceutical Co., originally was approved by the FDA in 2009 for the treatment of hyponatremia. In 2 pivotal phase 3 clinical trials, the drug, which inhibits the vasopressin V2 receptor, slowed kidney function decline in patients with ADPKD.
In the 1-year multicenter, randomized, double-blind REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) study, the estimated glomerular filtration rate (eGFR) declined by 2.34 mL/min/1.73 m2 per year among tolvaptan-treated patients compared with a decline of 3.61 mL/min/1.73 m2 per year among placebo recipients, a significant 1.27 mL/min/1.73 m2 difference in the annual rate of decline. Assuming tolvaptan treatment would continue to slow the decrement in the eGFR by 1.27 mL/min/1.73 m2 per year, the time to CKD stage 5 would be extended from 6.2 to 9.0 years, according to a report of the study's findings in the New England Journal of Medicine (2017;6;377:1930-1942). REPRISE was a multicenter, placebo-controlled double-blind trial that enrolled 1370 ADPKD patients aged 18–55 years with an eGFR of 25–65 mL/min/1.73 m2 or aged 56–65 years with an eGFR of 25–44 mL/min/1.73 m2.
In the 3-year multicenter double-blind TEMPO 3:4 (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan decreased the rate of decline in eGFR by 1.0 mL/min/1.73 m2 per year compared with placebo recipients among patients with earlier stages of ADPKD. Investigators randomly assigned 1445 patients aged 18–50 years who had ADPKD and estimated creatinine clearance of 60 mL/min or more.