- New analyses of data from a large trial of Novartis' Entresto found treatment with the drug reduced the rate of cardiovascular (CV) events by 20% compared to those taking another drug, even among patients considered clinically stable.
- The trial, called Paradigm-HF, also showed that clinically stable patients, meaning individuals with no history or very remote history of hospitalization for heart failure, were still at significant risk of CV events or death. Among stable patients who suffered a CV event, 51% died following their first event.
- This evidence supports the use of Entresto in patients with reduced ejection fraction heart failure (HFrEF) regardless of their prior medical history. Novartis wants to prove the value of Entresto across all patients with heart failure.
The FDA's approval of Novartis' Entresto in July 2015 was hailed as the beginning of a new era in the management of heart failure (HF) for the almost six million people in the U.S. who have HF. Novartis' data for Entresto is becoming a powerful evidence base for communicating value to payers.
However, uptake has been slower than expected since the drug's launch. Sales in the first six months were $21 million, with only $5 million coming in the fourth quarter. Part of the problem may lie with extended review times and slower reimbursement by U.S. payers. Continued positive data should help Novartis make its case for Entresto as access expands, however.
The PARADIGM-HF trial is the largest-ever clinical trial in HF patients, enrolling more than 8,000 HF patients. It was used as the basis for approval based on reduction of hospitalization and CV-related mortality in roughly 20% of patients, in addition to a 16% decrease in all-cause mortality.
The latest post-hoc analysis focused on patients with HFrEF. About half of HF patients fall into this category. The analysis showed the treatment benefit associated with Entresto extends to this population, not only in those patients who are considered clinically unstable, but also those patients who are deemed clinically stable. Moreover, the clinically stable patients continue to face a significantly higher risk of CV-related hospitalization and death without Entresto---and therefore also benefit from treatment.
Some patients in the study were receiving high- and low-dose beta-blockers, while others had been implanted with either a cardioverter-defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRT-D). Entresto was compared to with Vasotec (enalapril) for the study.
Establishing value for payers
"The data help inform the benefit of Entresto as a much needed medicine for a broad spectrum of heart failure patients, including in patients who are considered clinically stable, as well as those who are already being treated with guideline-directed background therapy," a spokesperson from Novartis said.
Earlier this year, Novartis agreed to performance-based pricing frameworks with two major U.S. insurers, Cigna and Aetna. The latest data analysis, which is being presented at this year's American Cardiology Conference in Chicago, is an important part of the data-set that will ultimately influence the success of its pay-for-performance deal with payers and set the tone for other companies.
"The specific terms of the contracts were negotiated separately and are confidential. However, the agreements use heart failure hospitalization as an outcome measure, based on the FDA-approved label. Novartis will reduce the price to payers, if the rate of heart failure hospitalization of patients on Entresto exceed a pre-specified threshold," according to Novartis.