FDA reviewer gives mixed recommendation on lixivaptan

An FDA reviewer recommended approval of lixivaptan from Cornerstone Therapeutics Inc. (NASDAQ:CRTX) for one of two proposed indications that will be discussed at Thursday's meeting of the Cardiovascular and Renal Drugs Advisory Committee. In briefing documents released Tuesday, the reviewer said "an argument can be made" for approval of lixivaptan for euvolemic hyponatremia associated with syndrome of inappropriate antidiuretic hormone (SIADH), with use restricted to inpatient initiation. However, the reviewer said FDA should issue a complete response letter in symptomatic hypervolemic hyponatremia associated with congestive heart failure (CHF).

The reviewer said lixivaptan had a "modest" effect on raising serum sodium in three Phase III trials, but also led to an increase in deaths in CHF patients compared to placebo in one of the trials (17.7% vs. 14.3%). The overall difference in deaths was not significant, according to the documents. However, the reviewer said post hoc analyses showed a "nominally significant" difference in patients who died soon after randomization or first dose. In 2010, the trial's data safety monitoring committee recommended termination of the trial, citing the death imbalance. ...