Who Owns Entresto?

Entresto (sacubitril/valsartan) was developed by Novartis as a first-in-class angiotensin receptor neprilysin inhibitor (ARNI). The drug combines two active ingredients: sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. This combination targets two pathways involved in heart failure progression.

The clinical development program was built on the PARADIGM-HF trial, a large-scale cardiovascular outcomes trial that enrolled over 8,400 patients. The trial was stopped early in 2014 by the Data Monitoring Committee because Entresto demonstrated a clear survival benefit compared to enalapril, the standard treatment at the time. Patients taking Entresto had a 20 percent reduction in cardiovascular death and a 21 percent reduction in heart failure hospitalizations compared to enalapril.

The FDA approved Entresto in July 2015 under priority review for heart failure with reduced ejection fraction. The European Medicines Agency approved it in November 2015. The drug received Breakthrough Therapy designation from the FDA, reflecting its potential to substantially improve outcomes for heart failure patients.

After approval, Entresto adoption was initially slower than Novartis expected. Physicians were cautious about switching patients from existing therapies. Novartis invested heavily in physician education and clinical evidence generation, publishing additional trial data and real-world evidence studies. The PIONEER-HF trial, published in 2018, demonstrated that initiating Entresto in stabilized acute heart failure patients reduced natriuretic peptide levels more than enalapril.

Entresto's sales grew steadily. By 2019, the drug had reached $1.8 billion in annual revenue. Sales accelerated after the 2021 FDA approval for heart failure with preserved ejection fraction (HFpEF), expanding the eligible patient population. By 2023, Entresto was Novartis's top-selling product, generating $6.0 billion. In 2024, sales reached $7.0 billion. In 2025, full-year sales were $7.7 billion, making Entresto one of the highest-revenue cardiovascular drugs in pharmaceutical history.

The primary U.S. composition of matter patent expired in July 2025. The FDA approved the first generic versions of Entresto in July 2025, manufactured by MSN Laboratories. Novartis filed a lawsuit against the FDA claiming the approval was unlawful, and submitted a Citizen Petition seeking to block generic entry until February 2026. The FDA rejected the petition, stating that generic manufacturers could avoid patent infringement by adjusting their labels. A federal appeals court ruled against Novartis, allowing generic Entresto to remain on the market.

Following generic entry, Entresto sales declined sharply. Q4 2025 revenue fell approximately 45 percent year-over-year. Novartis CEO Vas Narasimhan described the Entresto patent expiry as the largest in the company's history during an earnings call. Despite the revenue decline, Entresto remains on the market as a branded product, with Novartis continuing to promote its clinical benefits over generic alternatives.

Entresto is also subject to government price negotiation under the U.S. Inflation Reduction Act. Negotiated prices are scheduled to be published in September 2026 and would take effect in 2027. Narasimhan has described the initial impact of drug pricing negotiations as manageable.