FDA OKs Tolvaptan, First Treatment to Slow Kidney Function Decline

The US Food and Drug Administration (FDA) has approved tolvaptan (JYNARQUE) as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD), announced Otsuka Pharmaceuticals.

The approval is backed by data from the 2 phase 3 pivotal trials TEMPO 3:4 (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) and REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD).

The efficacy of JYNARQUE was demonstrated in the 2 pivotal trials that lasted 1 and 3 years, respectively. Data showed that JYNARQUE slowed kidney function decline in adults at risk of rapidly progressing ADPKD.

ADPKD is a progressively debilitating and usually painful genetic disorder that can lead to dialysis or kidney transplantation. It’s diagnosed in approximately 140,000 people in the US.

“The progression nature of ADPKD means that kidney function gets worse over time, eventually leading to end-stage renal disease. This progression happens more rapidly for some patients than others,” Michal Mrug, MD, associate professor, University of Alabama at Birmingham, investigator on REPRISE trial, said in a statement. “Today’s approval is great news for adults at risk of rapidly progressing ADPKD because by slowing the decline in kidney function, this therapy may give them more time before kidney transplant or dialysis.”

In the 1-year REPRISE study, the primary endpoint included 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. During the period, the change of eGFR from pretreatment baseline to post-treatment follow-up was 2.3 mL/min/1.73 m2/year with JYNARQUE versus −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 3-year TEMPO 3:4 study, JYNARQUE reduced the rate of decline in eGFR by 1.0 mL /min /1.73m2 /year (95 % confidence interval of 0.6 to 1.4) versus 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 2 years of treatment with JYNARQUE.

The most commonly observed adverse effects with an incidence >10% and at least twice that for placebo, were thirst, polyuria, nocturia, pollakiuria and polydipsia.

JYNARQUE can cause serious and potentially fatal liver injury, and acute liver failure requiring liver transplantation has been reported. It’s also been associated with elevations of blood alanine and aspartate aminotransferases with infrequent cases of concomitant elevations in bilirubin-total.

To ensure the safety of patients being treated with JYNARQUE, physicians should measure alanine and aspartate aminotransferases and bilirubin before treatment, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months after.

The treatment will be available in the US in the coming weeks in a 28-day treatment pack as an oral pill taken twice a day.

JYNARQUE is a selective vasopressin V2-receptor antagonist that’s indicated to slow kidney function decline in adults at risk of rapidly progressing ADPKD. The medication has been approved as treatment for adults with ADPKD in Japan, the EU, Canada, South Korea, Switzerland, Hong Kong, Australia, Turkey and Taiwan.