A positive recommendation from an FDA Advisory Committee has set Novartis’ Entresto (sacubitril/valsartan) on track to become the first drug to be approved for the treatment of heart failure with preserved ejection fraction (HFpEF). The potential label expansion could prove to be extremely lucrative for Novartis, providing the company with a first-mover advantage in this largely untapped market, says GlobalData, a leading data and analytics company.

The committee voted 12 to one that data presented from the PARAGON-HF trial support usage of Entresto, an angiotensin receptor neprilysin inhibitor (ARNI), in reducing worsening heart failure in HFpEF patients.

Fiona Chisholm, Pharma Analyst at GlobalData, comments: “The strong majority vote demonstrates a solid endorsement of the label expansion, despite a narrow miss for the composite primary endpoint (reduction in cardiovascular death and total heart failure hospitalizations) in the PARAGON-HF trial. This is indicative of the challenging HFpEF drug development landscape and the high level of unmet need that remains in the area.”

GlobalData estimates that there are 2.8 million patients diagnosed with HFpEF in the US in 2020 and this is projected to increase to 3.3 million by 2028, owing to global trends such as aging populations. According to GlobalData’s Pharma Intelligence Center’s clinical trial database, 29 HFpEF clinical trials have been initiated in the US since January 2010, although, until now, there have been no drug approvals resulting from these trials.

Chisholm continues: “The drug is already approved for heart failure with reduced ejection fraction (HFrEF) in over 100 countries worldwide. With so few options available for HFpEF disease management, there is essentially a low bar for new drug approvals in this area. Even therapies that demonstrate modest clinical benefits could gain marketing authorization and achieve significant uptake.”

The PARAGON-HF trial investigated the efficacy and safety of Entresto versus valsartan monotherapy in 4,822 patients with HFpEF. Although it may technically be regarded as a trial failure, Entresto treatment was associated with a relative reduction of 13% in the primary composite endpoint of cardiovascular death and total heart failure hospitalizations, relative to valsartan (p=0.059).

Chisholm adds: “Novartis maintains that Entresto confers a treatment benefit in HFpEF, emphasising the narrow miss for statistical significance, a factor that is likely to have been pivotal to the committee’s positive recommendation. Entresto could be approved for HFpEF as early as Q1 2021, if the FDA follows its committee’s advice.”