FDA Panel Votes in Favor of Sacubitril/Valsartan for New Heart Failure Indication

A US Food and Drug Administration (FDA) Advisory Committee has voted in favor of supporting an indication for sacubitril/valsartan (Entresto) after clinicians and representatives from Novartis argued the treatment’s effects in patients with heart failure with preserved ejection fraction (HFpEF).

The 12 to 1 vote by members of the US FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) indicate a favorable response to data from the PARAGON-HF study, which fell just short of proving statistical significance in reducing heart failure hospitalizations and death in HFpEF patients with a P-value of .06.

“Managing HFpEF has historically been a clinical and scientific challenge due to the heterogeneity of the condition,” said Scott Solomon, MD, Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital, and PARAGON-HF Executive Committee Co-Chair, in a statement. “Today’s vote represents much needed progress in this area of unmet need and is a positive step toward bringing a potential therapy to millions of patients suffering from this type of heart failure.”

Having already received approval for treatment of patients with HFrEF in 2014, the vote in favor of sacubitril/valsartan represents a major step towards a therapy approved to reduce risk of hospitalizations and death in patients with HFpEF. With their supplemental new drug application for HFpEF accepted during July 2020, a decision on an indication for sacubitril/valsartan is expected in Q1 2021.

The FDA’s CARDC, which met on December 15, examined data from the phase 3 PARAGON-HF trial as well as from the PARAMOUNT and PARADIGM-HF trials. If approved, sacubitril/valsartan would be set up to fill a major treatment gap and also become the first therapy approved to treat patients with both HFpEF and HFrEF.

"Our commitment to reimagine medicine through our extensive clinical trials program on heart failure has been unwavering, and we are encouraged by the Committee's response today," said David Soergel, MD, Global Head of Cardiovascular, Renal and Metabolic Drug Development, Novartis, in the aforementioned statement. "We appreciate the valuable insights shared by the patient and advocacy community about this devastating disease, and we look forward to FDA's decision on the potential approval of this new indication."

For more on the use of sacubitril/valsartan in patients with HFpEF, check out this interview from ESC 2020 with Burkert Pieske, MD, professor of medicine and director of cardiology at Charite University Medicine, who presented results of the PARALLAX.