Novartis said its phase-3 Paragon-HF trial on heart failure treatment Entresto (ingredient: sacubitril/valsartan) failed to meet the objectives. The drug had been expected as one of the key growth engines for the Swiss drugmaker.
The company announced on Monday that the Paragon-HF trial “narrowly missed statistical significance for its composite primary endpoint of reducing cardiovascular death and total heart failure hospitalizations.”
Entresto is an authorized treatment for patients with heart failure with reduced ejection fraction (HFrEF) who have left ventricular systolic dysfunction. Novartis has been conducting the Paragon-HF study since 2014 to expand Entresto’s target patients to heart failure patients with preserved ejection fraction (HFpEF).
About half of all heart failure patients, some 13 million people worldwide, are estimated to suffer from HFpEF, according to Novartis. There is no approved treatment for HFpEF patients.
Novartis has been pushing to expand Entresto’s indication for HFpEF patients and declared the treatment as the company’s primary growth item.
First approved in 2015, Entresto has shown slow growth in sales. However, recent changes in the prescriptions for chronic heart failure led to a steep sales growth of the drug.
In the first half-year, Entresto’s global revenue reached $778 million, up 80 percent from a year earlier.
Novartis anticipated that Entresto would raise $3 billion annual sales globally with the existing indication for HFrEF alone. An expanded indication for HFpEF patients would boost the annual revenue up to $5 billion per year, the company had predicted.
However, the latest failure of the Paragon-HF trial is likely to take a toll on the company’s estimated revenue growth.
The Paragon-HF trial compared Entresto’s efficacy and safety with those of valsartan in 4,822 patients with HFpEF. The study evaluated the composite primary endpoint of total heart failure hospitalizations and cardiovascular death.
“Even though Entresto narrowly missed statistical significance for its composite primary endpoint, we reconfirmed its overall safety profile,” said John Tsai, M.D., Global Drug Development and Chief Medical Officer, Novartis. “The totality of evidence from the trial suggests that treatment with Entresto may result in clinically important benefits in HFpEF.”
He went on to say that the company would discuss potential next steps with clinical experts and regulators, adding that Novartis was preparing to present the study’s full results at the European Society of Cardiology (ESC) Congress in September.