FDA Advisory Panel To Review New Heart Failure Drug From Novartis

A novel acute heart failure drug from Novartis will be evaluated next month by an FDA advisory committee, perhaps countering a long string of crash-and-burn cardiology drugs. On February 13 the FDA's Cardiovascular and Renal Drugs Advisory Committee will discuss the biologics license application (BLA) for serelaxin injection from Novartis. The indication is for the improvement of the symptoms of acute heart failure through reduction of the rate of worsening of heart failure. (The meeting notice has been posted in the Federal Register but has not yet appeared on the FDA website.) Last year the drug received a "breakthrough therapy" designation from the FDA.

Serelaxin is a recombinant form of the naturally occurring human hormone relaxin-2, which has been found to help women adjust to the cardiovascular changes that occur during pregnancy. If approved it could become the first significant new treatment for acute decompensated heart failure patients in a generation.

The main source of information about serelaxin is the RELAX-AHF trial, which was published in the Lancet in 2012. Serelaxin treatment in RELAX-AHF appeared to be safe and led to a significant reduction in one measure of dyspnea relief, although the committee will undoubtedly spend time discussing the failure to show improvement in another measure of dyspnea that was a co-primary endpoint. When the trial results were presented at the American Heart Association the trial discussant, John McMurray, said that he believed serelaxin "does improve dyspnea and other symptoms and signs of congestion" but wondered about the clinical significance of the magnitude of the improvement and, also, whether the single trial would be sufficient to gain marketing approval.

Although treatment with serelaxin had no effect on hospital readmission there was a highly surprising and controversial reduction in mortality at 6 months. As I reported at the time, the trial investigators acknowledged that the findings of a six month survival benefit “for a drug given for 48 h with a moderate number of death events (107 total) raises the question of whether this benefit is due to chance and whether another, confirmatory trial should be done.” Heart failure expert Milton Packer said that “if the mortality effect is true then this trial changes the way we do things.” But, he emphasized, ”the real question is whether the mortality difference seen in this trial is true and replicable.”

One reason for caution is that the last drug approved for acute heart failure, nesiritide (Natrecor, Johnson & Johnson ) was the subject of almost a decade of controversy and ended up with a criminal fine for the company.