Novartis HF drug sacubitril/valsartan fails trial

Swiss drugmaker Novartis on July 29 announced its combo sacubitril/valsartan drug Entresto “narrowly missed” its primary endpoint in the Phase III PARAGON-HF study, throwing into question the future of a blockbuster drug.

Basel-based Novartis said in a statement the totality of evidence from the trial suggests treatment with sacubitril/valsartan “may result in clinically important benefits” in patients with heart failure with preserved ejection fraction (HFpEF), but it failed to top its active comparator, valsartan, in reducing CV death and total HF hospitalizations in HFpEF patients. While sacubitril/valsartan was approved in 2015 as an effective treatment for heart failure with reduced ejection fraction (HFrEF), there are currently no federally approved therapies for HFpEF.

“The trial narrowly missed statistical significance for its composite primary endpoint,” Novartis said in its statement. “Safety and tolerability were consistent with previously reported sacubitril/valsartan data.”

Reuters reported previously that twice-a-day Entresto, used exclusively in patients with HFrEF, had the potential to generate $3 billion in sales annually. That would qualify sacubitril/valsartan as a blockbuster drug—one that ropes in at least $1 billion each year—but Novartis Pharmaceuticals CEO Paul Hudson told Reuters that number could climb to $4 billion or $5 billion if the drug was extended to HFpEF patients.

According to Physician’s Weekly, Novartis shares dropped 1.4% to 91.20 Swiss francs, or $91.90, in Zurich following the news that Entresto had failed to meet its primary endpoint in the PARAGON-HF trial. Entresto already had a slow start on the U.S. market in 2015, but its revenue rose around 90% in the first half of 2019, suggesting its use was on the up-and-up.

“The milder the disease the higher the hurdle,” analyst Michael Nawrath, of Zuercher Katonalbank, told Physician’s Weekly. Nawrath said the likelihood of a positive outcome in the PARAGON-HF trial had always been low. 

“It would have been very good for the momentum of Novartis, whose shares would have passed the 100 franc per share mark, on a positive outcome. Despite the relatively lower expectations, we are talking about a negative but not sustained price reaction.”

Novartis said it’s continuing to study sacubitril/valsartan in HFrEF patients, with new data on cardiac remodelling slated for presentation at the ESC Congress in Paris next month. More detailed results of the PARAGON-HF study will also be released at that time, and the company said additional studies investigating sacubitril/valsartan in HFpEF patients are “ongoing.”