Doctors finally got a look at the data on Novartis’ new heart failure drug LCZ696 at the European Society of Cardiology (ESC) meeting over the weekend, and have already started talking about rewriting treatment guidelines on the strength of the study.
Expectations were already running high when Novartis release top-line data from the PARADIGM-HF trial in March, having stopped it early after the drug was found to help patients with heart failure and low ejection fraction live longer and avoid hospitalisation.
Now the full set of numbers behind the decision is available, and at ESC it was revealed that LCZ696 cut cardiovascular deaths by 20% versus standard therapy based on the ACE inhibitor enalapril, while also reducing hospitalisations by 21% and all-cause mortality by 16%.
To put the results in perspective, enalapril has demonstrated improved survival over placebo by 15%, so LCZ696 is effectively more than doubling the effect of the comparator drug.
Patients in the trial received either LCZ696 – a combination of angiotensin II receptor antagonist valsartan with a neprilysin blocker called sacubitiril that boosts its effects – or enalapril on top of current best treatment.
Safety data from the trial demonstrated the drug was also well-tolerated, with around 11% of patients on LCZ696 discontinuing study medication for any adverse event, compared to just over 12% of those on enalapril.
One of the principal investigators in the trial, Milton Packer of Texas Southwestern Medical Centre in the US, said PARADIGM-HF was specifically designed to compare LCZ696 with standard therapy and provide evidence – on its own – that would support a guideline change.
With more than 8,400 patients it is the largest trial ever conducted in heart failure and used the gold standard for heart failure therapy as a control, he told reporters at the ESC. The data have also been published in the New England Journal of Medicine.
Novartis has already said it plans to file for approval of LCZ696 this year and – assuming the FDA agrees with the overwhelmingly positive view of the data – it looks almost certain to have a major blockbuster on its hands.
An editorial accompanying the trial report in the NEJM by Mariell Jessup of the University of Pennsylvania writes that LCZ696 “may prove to be the first disruptive agent to the heart-failure treatment algorithm, which has remained essentially unchanged for a decade.”
“The beneficial results seen in PARADIGM-HF may apply to a wide spectrum of patients, even those who are currently receiving the best possible therapy,” she added.
Analysts have suggested LCZ696 could eventually bring in between $8bn and $10bn a year at peak, providing it also shows a benefit in patients with heart failure and preserved ejection fraction which is being tested in a separate study.
Novartis also looks likely to be on its own in the marketplace for some time, with no other angiotensin receptor neprilysin inhibitor currently advancing through clinical development.