Otsuka Presents Short- and Long-Term Data on Heart Failure Drug

Otsuka has announced trial results showing that once-daily dosing with its investigational oral medication tolvaptan, a vasopressin receptor antagonist, was associated with improvements in signs and symptoms of acutely decompensated heart failure (ADHF) in hospitalized patients receiving conventional care, without an adverse effects on their long-term survival, versus placebo.

The data is from the short- and long-term analyses of the international EVEREST trial, published in the March 28 issue of The Journal of the American Medical Association and presented at the American College of Cardiology's recent meeting in New Orleans.

The Phase III trial, involving a total of 4,133 ADHF patients, represents three studies: a long-term outcomes trial evaluating patients after their discharge for a minimum of 60 days of treatment and two identical, embedded short-term pivotal studies that examined tolvaptan compared with placebo over seven days of inpatient care or discharge, whichever came first.

Data from the two short-term studies documented that tolvaptan treatment yielded significantly greater improvements than placebo based on the primary endpoint, which was the composite score of changes in patient-assessed global clinical status and changes in body weight at day seven or discharge. Long-term tolvaptan use did not differ from placebo on either of the study's two primary endpoints: deaths from all causes or from the combined endpoint of cardiovascular deaths or subsequent hospitalization for worsening heart failure.

Tolvaptan is a novel, investigational small molecule designed to be an antagonist of the vasopressin V2 receptor, which plays a role in the kidney's regulation of fluid excretion. The majority of patients hospitalized for ADHF have edema or excess body fluid, which is treated with diuretics to excrete the fluid, according to Otsuka. In contrast to diuretics, tolvaptan is designed to promote aquaresis, the excretion of electrolyte-free water.