Novartis is banking on a broader label to expand the reach of its blockbuster heart med Entresto, but in patients who've suffered prior heart attacks, the drug just hit a setback.
In the phase 3 Paradise-MI trial, Entresto missed its primary endpoint to reduce the risk of cardiovascular death and heart failure after an acute myocardial infarction, Novartis quietly revealed in its first-quarter earnings statement. In the study, "numerical trends consistently favored" the drug against standard of care ramipril, but Entresto fell short of its goal. Novartis says it'll “continue to evaluate the data.”
“In light of the results, we are conducting additional analyses to understand the data fully in the context of Entresto’s clinical profile,” a Novartis spokesperson said via email. The company plans to roll out topline results at the American College of Cardiology 70th Annual Scientific Session on May 15.
Novartis kicked off the Paradise-MI study in 2016 to see whether Entresto could top the widely used ACE inhibitor ramipril at reducing cardiovascular death and heart failure after patients have had a heart attack. The company aims to position Entresto as an option for the 800,000 patients in the U.S.—and the roughly 7 million patients worldwide—who suffer from these heart attacks each year. Around one in four out of those 7 million subsequently develop heart failure.
The 5,669-subject study pitted 200 mg Entresto against a 5 mg dose of ramipril. Both drugs were given twice a day in addition to standard post-heart attack treatment.
Meanwhile, on the sales front, the medicine turned in an impressive performance during the first quarter. Sales for the drug jumped 39% to $789 million, helping Novartis offset troubles in its generics business.
Entresto's trial setback comes shortly after a major win for Entresto in its bread-and-butter heart failure indication. The FDA in February cleared the drug in heart failure with preserved ejection fraction (HFpEF) for patients whose left ventricular ejection fraction (LVEF) is below normal.
On top of Entresto’s existing nod in patients with chronic heart failure and reduced ejection fraction, that approval positioned the drug as the first and only medicine cleared in both conditions. The new label also paved the way for Novartis to target roughly 5 million of the 6 million Americans diagnosed with chronic heart failure, the company said.
Some 2 million patients with LVEF below normal "did not previously have an approved treatment beyond symptom relief and management of comorbidities," a Novartis spokesperson told Fierce Pharma in February. The company said it would move fast to raise the drug’s profile, with plans to “immediately” deploy field representative for doctor discussions.
That indication could boost Entresto’s peak sales estimate to the tune of $1 billion, Jefferies analyst Peter Welford wrote to clients last year when an independent FDA panel backed the drug in HFpEF. As for the failed trial, Welford noted that post-heart attack patients only made up $525 million of the $5.1 billion global peak sales Jefferies had estimated for Entresto.
With $2.5 billion in 2020 sales, Entresto became Novartis’ third-largest revenue generator last year.