ESC – Novartis heart failure pill scores big

One of the most keenly awaited data points of the year, release of pivotal heart failure data for Novartis’s LCZ696, did not disappoint. The combination pill reduced the risk of cardiovascular death or hospitalisation by 20% compared with enalapril, leading its chief investigator to argue that the new drug should replace the standard of care.

The pill also decisively hit separate secondary endpoints of prevention of cardiovascular death and hospitalisation as well as death from any cause, while not raising any safety issues such as incidence of angioedema. More data are set to emerge tomorrow (Sunday) at an ESC hotline session, and no doubt cardiologist are eager to see its safety and tolerability profile in detail and how consistent its effects are across subgroups.

Big expectations

The table was set for Novartis when the Paradigm-HF trial’s data and safety monitoring board stopped it early because of conclusive positive benefit, but the Swiss group held back data to present to European cardiologists (Novartis gets surprise heart failure win as ACC data roll in, March 31, 2014).

Because the threshold for an early termination was a 15% mortality/hospitalisation benefit over enalapril – Merck & Co’s Vasotec – LCZ696’s performance was assumed to be outstanding. Sales forecasts have skyrocketed, and now stand at $2.2bn in 2020. Analysts from Jefferies wrote earlier this month that cardiologists would view a 15% relative risk reduction against enalapril to be clinically significant.

On the primary endpoint, a composite of cardiovascular death or hospitalisation after more than two years of treatment, patients taking LCZ696 were 20% less likely to have died or been hospitalised from cardiovascular causes, 20% less likely to have died because of cardiovascular causes, 16% less likely to have died from any cause, and 21% less likely to have gone into the hospital because of heart failure.

Bernstein analyst Timothy Anderson wrote today that the results were at the high end of investor expectations.

Milton Packer, a cardiologist at University of Texas Southwestern, noted in his presentation on the Paradigm findings that the current standards of care, the ACE inhibitors and angiotensin receptor blockers, reduced the risk of death by about 18% when they were introduced, and this represents a significant improvement over that.

“The finding that LCZ696 had a 20% greater effect on cardiovascular mortality than ACE inhibitor strongly supports the conclusion that LCZ696 should replace the current use of ACE inhibitors and ARBs in chronic heart failure,” Dr Packer said.

Commenting on the Paradigm trial results, Michael Komajda, cardiology professor at the University of Pierre et Marie Curie in Paris, agreed that the results reflect well on LCZ696, but cautioned that many payers will be looking for evidence that it does not end up a significantly more expensive alternative.

“This trial is the first contemporary trial to propose a substitution rather than an add-on strategy in chronic heart failure,” said Michael Komajda, cardiology professor at the University of Pierre et Marie Curie in Paris. “The magnitude of the risk reduction as well as the number of patients needed to prevent [negative] outcomes suggest this is cost-effective. However, pricing will be key, and economic studies are therefore eagerly awaited.”

Should Novartis get its launch strategy right, the already heady sales forecasts will only go higher.

To contact the writer of this story email Jonathan Gardner in Barcelona at [email protected] or follow @JonEPVantage on Twitter

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