FDA reviewers bearish on Otsuka's tolvaptan

FDA reviewers recommended against approval of an NDA for tolvaptan from Otsuka Pharmaceutical Co. Ltd. (Tokyo, Japan) to slow kidney disease in adults with rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). Reviewers said tolvaptan slowed the loss of renal function in a Phase III trial but because of missing data the treatment effect was "unclear." The reviewers also said the trial enrolled patients with relatively preserved renal function, which makes it "difficult to project tolvaptan's likely benefit in delaying the onset of end-stage renal disease" in patients with more advanced ADPKD. Additionally, the reviewers said tolvaptan's safety profile "was not reassuring," citing a high rate of liver injury in ADPKD patients receiving the vasopressin 2 (V2) receptor antagonist. ...