FDA approved Jynarque (tolvaptan) for Autosomal Dominant Polycystic Kidney DiseaseFDA approved Jynarque to Slow Kidney Decline in Adults with a Genetic Kidney Disease

Jynarque is a selective vasopressin V2-receptor antagonist.

Jynarque is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

The initial dosage is 60 mg orally per day as 45 mg taken on waking and 15 mg taken 8 hours later. Titrate to 60 mg plus 30 mg, then to 90 mg plus 30 mg per day if tolerated, with at least weekly intervals between titrations. Patients may down-titrate based on tolerability. Encourage patients to drink enough water to avoid thirst or dehydration. If a dose is missed, take the next dose at its scheduled time. For patients taking moderate CYP3A inhibitors, reduce the dose per Table 1: standard 90 mg and 30 mg becomes 45 mg and 15 mg; standard 60 mg and 30 mg becomes 30 mg and 15 mg; standard 45 mg and 15 mg becomes 15 mg and 15 mg. Interrupt Jynarque temporarily for short-term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available. Concomitant use of strong CYP3A inhibitors is contraindicated.

Jynarque was shown to slow the rate of decline in renal function in adult patients at risk of rapidly progressing ADPKD in two trials: TEMPO 3:4 in patients at earlier stages of disease and REPRISE in patients at later stages. The findings from these trials, when taken together, suggest that Jynarque slows the loss of renal function progressively through the course of the disease.

TEMPO 3:4 was a Phase 3, double-blind, placebo-controlled, randomized trial in early, rapidly-progressing ADPKD. It enrolled 1445 adult patients (age >18 years) with early (estimated creatinine clearance [eCrCl] ≥60 mL/min), rapidly-progressing (total kidney volume [TKV] ≥750 mL and age <51 years) ADPKD (diagnosed by modified Ravine criteria), randomized 2:1 to tolvaptan or placebo. Patients were treated for up to 3 years. The primary endpoint was the intergroup difference for rate of change of TKV normalized as a percentage. The key secondary composite endpoint (ADPKD progression) was time to multiple clinical progression events: worsening kidney function, medically significant kidney pain, worsening hypertension, or worsening albuminuria. At baseline, average estimated glomerular filtration rate (eGFR) was 82 mL/min/1.73 m2 and mean TKV was 1692 mL. The trial met its prespecified primary endpoint of 3-year change in TKV (p<0.0001).

REPRISE trial data are not available in the label.

To mitigate the risk of significant or irreversible liver injury, perform blood testing for ALT, AST and bilirubin prior to initiation of Jynarque, at 2 and 4 weeks after initiation, monthly for 18 months and every 3 months thereafter. Monitor for concurrent symptoms that may indicate liver injury. Concomitant use of strong CYP3A inhibitors is contraindicated. Dose adjustment is recommended for patients taking moderate CYP3A inhibitors.

Jynarque is indicated to slow kidney function decline in adults at risk of rapidly progressing ADPKD. The label states that the findings from TEMPO 3:4 and REPRISE, when taken together, suggest that Jynarque slows the loss of renal function progressively through the course of the disease.