FDA Approves Otsuka's Jynarque as First Treatment to Kidney Decline in Rapidy Progressing Autosomal Dominant Polycystic Kidney Disease (ADPKD)

  • ADPKD, the fourth leading cause of end-stage renal disease,1,2 is a progressively debilitating genetic disease characterized by the development of fluid-filled cysts in the kidneys
  • Data from two phase 3 clinical trials showed that Jynarque (tolvaptan) slowed kidney function decline in adults at risk of rapidly progressing ADPKD
  • Jynarque can cause serious and potentially fatal liver injury. Due to elevations of liver enzymes in the blood associated with Jynarque, this medication will be available only through a restricted distribution program and patients will need to be monitored for elevations in these enzyme levels
  • Jynarque will be sold in a 28-day treatment pack at a wholesale acquisition cost of $13,041.10.

Otsuka announced on 4/24/18 that the U.S. Food and Drug Administration (FDA) has approved Jynarque (tolvaptan) as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

The efficacy of tolvaptan was demonstrated in two pivotal trials, lasting one year and three years, respectively. In the one-year REPRISE study, the primary endpoint was the treatment difference in the change of eGFR from pretreatment baseline to post-treatment follow-up, annualized by dividing by each subject’s treatment duration. In the randomized period, the change of eGFR from pretreatment baseline to post-treatment follow-up was −2.3 mL/min/1.73 m2/year with tolvaptan as compared with −3.6 mL/min/1.73 m2/year with placebo, corresponding to a treatment effect of 1.3 mL/min/1.73 m2/year (p <0.0001). In the three-year TEMPO 3:4 study, tolvaptan reduced the rate of decline in eGFR by 1.0 mL /min /1.73m2 /year (95 % confidence interval of 0.6 to 1.4) as compared to placebo in patients with earlier stages of ADPKD. In the extension trial, eGFR differences produced by the third year of the TEMPO 3:4 trial were maintained over the next 2 years of Jynarque treatment.

ADPKD is a genetic disease with consequences that can lead to dialysis or kidney transplantation. It is a progressively debilitating and often painful disorder in which fluid-filled cysts develop in the kidneys over time. These cysts enlarge the kidneys and impair their ability to function normally, leading to kidney failure in most patients. ADPKD is diagnosed in approximately 140,000 people in the U.S.,  and impacts families across multiple generations, since a parent with ADPKD has a 50 percent chance of passing the disease on to each of their children.