Entresto Receives Positive Opinion From CHMP for Pediatric Heart Failure

Hope may be on the horizon for pediatric patients aged 1 month to younger than 18 years living with symptomatic chronic heart failure, in Europe, following a positive opinion on Entresto (sacubitril/valsartan, Novartis) from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency.

The opinion means the CHMP recommends approval of the treatment for pediatric patients.

The combination medication has been approved for use in adult patients in the United States and European Union since 2015, and it was approved by the FDA for use in the United States among patients 1 year or older with symptomatic HF and systemic left ventricular systolic dysfunction on October 2, 2019.

Final data from the phase 3 PANORAMA-HF and data extrapolated from the phase 3 PARADIGM-HF trial provided the basis for this positive opinion, according to a press release from Novartis.

“This positive opinion paves the way towards Novartis being able to provide children diagnosed with heart failure due to left ventricular systolic dysfunction in the European Union and their families with an effective therapy in an age-appropriate formulation, helping to address what is a major unmet need,” said David Soergel, MD, global head, Cardiovascular, Renal and Metabolism Development Unit, Novartis, in the statement announcing the opinion.

Among pediatric patients, there is a 20-times greater risk of death from heart failure, and of those hospitalized for a cardiac condition, 33% of those admission are related to heart failure, according to data published in 2018 and 2019.

The PANORAMA-HF, the largest ever trial to investigate treatment for pediatric heart failure—30 countries and 105 clinical sites in North America, Europe, Asia, and Latin America—was conducted in 2 parts: Part 1 determined optimal dosing, and part 2 compared outcomes following 52 weeks of treatment with Entresto vs enalapril. All patients were 1 month to younger than 18 years with New York Heart Association/Ross Class II-IV disease, with heart failure reduced ejection fraction (HFrEF; < 45% or fractional shortening < 22.5%). Overall findings demonstrated a reduction in N-terminal pro–brain natriuretic peptide (NT-proBNP), high levels of which indicate reduced pumping capacity in the heart and the severity of heart failure.

PARADIGM-HF was conducted among an adult patient population with HFrEF (40% or less for this analysis), but once again compared outcomes with enalapril. The trial ended early after the “boundary for overwhelming benefit had been crossed.” Among the treatment population, there was a 20% reduced risk for death from cardiovascular causes or heart failure–related hospitalization, a 21% reduced risk of heart failure–related hospitalization, and decreased symptoms and physical limitations from heart failure. Compared with the enalapril group, fewer patients receiving sacubitril/valsartan also had renal impairment, hyperkalemia, and cough.

At present, there are more than 40 trials being conducted within Novartis’ FortiHFy global clinical program that is investigating patient outcomes from heart failure and generating real-world evidence on Entresto.

Reference

Novartis Entresto receives positive CHMP opinion for pediatric heart failure. News Release. Novartis. March 31, 2023. Accessed April 3, 2023. https://bit.ly/3GesiBU