The FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) will meet this Thursday to discuss the NDA for Cornerstone Therapeutics’ (NASDAQ:CRTX) lixivaptan for the treatment of hyponatremia (low sodium) associated with heart failure. FDA briefing documents were released on Tuesday morning ahead of Thursday’s panel. The documents are geared to focus on the risks and criticism of the drug and its clinical trials, and while those are cited, the highly statistical significance in three phase III trials suggest that the drug will get a favorable nod from the panel for approval. One of the panel reviewers, Dr. Nancy Xu, said that of the two indications for lixivaptan – for the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and for congestive heart failure – only the first should be approved by the FDA. Xu cited an imbalance in deaths between the lixivaptan and placebo arms of the BALANCE trial (testing against heart failure). The safety concern prompted the data safety monitoring committee to issue a letter in June 2010 urging termination of the trial, however, no specific factor was found to be associated with the imbalance since. Although all three trials showed highly statistical significant results, the treatment effects on serum sodium appeared small (1.2 mmol/L in BALANCE, 2.2 mmol/L in LIBRA and 2.4 mmol/L in HARMONY).
The risks and benefits from lixivaptan will be need to be carefully weighed before a vote and approval, however, analysts are guiding for a vote of approval for hyponatremia with SIADH, if not for both indications. Shares should trade up on the news, and could top $8 if the panel makes a recommendation for approval. Lixivaptan’s PDUFA date is October 29 and will take the CRDAC’s decision into consideration for the final decision.