Novartis' Entresto Shows Mixed Results in New Study for HFpEF Patients

Compiled by Fan Dongdong

Recently, according to the latest report presented by Novartis at the European Society of Cardiology Annual Congress, Entresto has achieved success in improving symptom severity and cardiac function in patients with heart failure with preserved ejection fraction (HFpEF).

It was reported that Entresto improved serum NT-proBNP levels (a marker for assessing the severity of heart failure) in patients at week 24 of the trial; however, this outcome was also observed in patients receiving valsartan, ACE inhibitors, or placebo. Entresto did not demonstrate a statistically significant advantage over other drug groups in improving the six-minute walk distance. Regarding secondary endpoints, the drug improved quality of life after 24 weeks but failed to surpass the control group.

Entresto is a fixed-dose combination of valsartan and the neprilysin inhibitor sacubitril. Novartis hopes that Entresto will become the first drug approved for the treatment of patients with heart failure with preserved ejection fraction (HFpEF). Based on current trial results, the prospects for this drug appear to be mixed. It is understood that Entresto was approved by the U.S. FDA in July 2015 for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). In July 2017, the drug was approved for marketing in China.

In June 2019, Novartis announced the full results of the global Phase III PARAGON-HF study of Entresto. This randomized, double-blind, parallel-group, active-controlled trial enrolled a total of 4,822 patients with heart failure with preserved ejection fraction (HFpEF) and evaluated the efficacy and safety of Entresto compared with the active control, valsartan, in this patient population. The trial results showed that Entresto reduced the composite endpoint of total (first and recurrent) heart failure hospitalizations and cardiovascular (CV) death by 13%, which was not statistically significant. Although the study missed its primary endpoint, it still holds promise.

SVB Leerink analysts noted, however, that later this year, Novartis pointed out that subgroup analyses of the trial could provide a basis for future studies and potentially support more limited approvals, as the data appeared to resonate with cardiologists. In November last year, Novartis stated that heart failure patients with an ejection fraction below 57% demonstrated a stronger clinical response to Entresto than those with an ejection fraction above this threshold. Meanwhile, Entresto’s position as the leading heart failure medication among cardiologists may bode well for its future sales.

In a July physician survey, SVB Leerink analysts found that doctors generally held a positive view of the clinical efficacy of Entresto in patients with HFrEF, and widely believed that sales of the drug would grow rapidly in the coming years as more physicians tend to prescribe Entresto.

Regarding competitors, AstraZeneca’s SGLT2 inhibitor Farxiga received FDA approval in May for the treatment of patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes. Meanwhile, Eli Lilly and Boehringer Ingelheim are also working toward obtaining approval for the SGLT2 inhibitor Jardiance.

Currently, Entresto is Novartis’s latest growth driver. The drug saw a 74% increase in the fourth quarter of 2019, reaching $1.7 billion for the full year, with annual sales rising 68% year-over-year. In the first quarter of 2020, total revenue from the drug amounted to $569 million.

References:

1.Novartis PARAGON-HF trial suggests Entresto® benefit in HFpEF patients but narrowly misses primary endpoint

2.ESC: Novartis' Entresto racks up a heart failure study win—but it's a mixed one