FDA OKs Expanded Indication for Heart Failure Treatment

Officials with the FDA has approved an expanded indication for Novartis’ heart failure (HF) therapy sacubitril/valsartan (Entresto).¹

The new approval indicates sacubitril/valsartan for the reduction of the risk of cardiovascular death and hospitalization for HF in adult patients with chronic HF. The benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal, according to Novartis. However, the label states that LVEF is a variable measure and clinical judgement should be used in deciding whom to treat.

This latest indication is based on efficacy and safety data from the phase 3 PARAGON-HF clinical trial, which evaluated sacubitril/valsartan in patients with guideline-defined HF with preserved ejection fraction (HFpEF).

In PARAGON-HF, a total of 4822 patients were randomly assigned to sacubitril/valsartan or valsartan. Patients in the study were required to have signs and symptoms of HF, a LEVF of 45% or greater, evidence of natriuretic peptide elevation, and structural heart disease. The median follow-up was 34 months. According to an FDA review, the trial overall fell short in meeting its primary end point in reducing total hospitalization and cardiovascular death in patients with HFpEF, but the data suggested benefit in certain patient groups. According to the results, there was greater benefit in patients with ejection fraction below the median of 57%, with a 22% reduction rate, and in women, with a 28% reduction rate (rate ratio 0.73; 95% CI 0.59-0.90) in the primary end point.²

“This approval is a significant advancement, providing a treatment to many patients who were not eligible for treatment before because their ejection fraction was above the region we normally considered reduced,” Scott Solomon, MD, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and PARAGON-HF executive committee co-chair, said in a statement.1 “Until now, treatment for these patients was largely empiric. We can now offer a treatment to a wider range of patients who have an LVEF below normal.”

An FDA panel voted to recommend the expanded use of sacubitril/valsartan for patients with HFpEF in December based on the PARAGON-HF study, as well as additional evidence from the PARAMOUNT and PARADIGM-HF trials.

References

1. Novartis Entresto® granted expanded indication in chronic heart failure by FDA. News release. Novartis; February 16, 2021. Accessed February 16, 2021. https://www.novartis.com/news/media-releases/novartis-entresto-granted-expanded-indication-chronic-heart-failure-fda

2. FDA. Cardiovascular and Renal Drugs Advisory Committee Meeting, December 15, 2020. FDA briefing document. December 15, 2020. Accessed February 16, 2021. https://www.fda.gov/media/144377/download