Chronic HF Trial of Novartis Agent Halted Early for Benefit

April 02, 2014

BASEL, SWITZERLAND — A large trial sponsored by Novartis has closed shop early because patients with chronic heart failure taking its drug LCZ696 instead of the ACE inhibitorenalapril were already living longer with fewer HF hospitalizations, the company has announced[1].

"This follows two previous interim analyses that showed the safety profile of LCZ696 was acceptable," according to Novartis in a press release, aimed at the investment community, on the phase 3 PARADIGM-HF trial's early termination.

If its early findings are borne out by fuller analysis and probably by other studies, the new drug class, dubbed angiotensin-receptor neprilysin inhibitors (ARNIs), could potentially supplant ACE inhibitors as a mainstay of HF treatment. ARNIs are inhibitors of the renin-angiotensin system and also boost endogenous natriuretic-peptide levels.

LCZ696 has already shown promise as a hypertension treatment; patients who received it rather than the angiotensin-receptor blocker (ARB) valsartan in a large 2010 trial had steeper blood-pressure reductions, as reported by heartwire .

The prospects for LCZ696, should it become available, are especially striking, given that ACE inhibitors and ARBs are already considered success stories in heart failure and hypertension.

The drug also tantalized in patients with HF with preserved ejection fraction, a group for which no solid drug therapies are now available, in a small study that also compared it with valsartan.

PARADIGM-HF randomized 8436 patients in NYHA class 2 to 4 heart failure with LV ejection fractions no higher than 35%, plus elevated natriuretic peptides, to receive LCZ696 at 200 mg twice daily or enalapril at 10 mg twice daily.

The trial, conducted at >1000 sites in more than 50 countries in the Americas, Europe, and Asia, followed patients for the primary end point of time to first CV death or HF hospitalization. Novartis didn't say how long the follow-up had averaged when it stopped the trial.

The exuberant PARADIGM-HF announcement lets Novartis rebound somewhat from the hit it took at last week's meeting of an FDA advisory panel, which unanimously declined to recommend approval of its application for serelaxin in patients with acute heart failure.

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