How to save 28,000 heart patients a year? Use Novartis' Entresto, JAMA says

Entresto bottles

Novartis has some new Entresto data to add to its case. Researchers crunched numbers on U.S. heart failure patients and associated spending to show that Entresto is as cost-effective as the standard generic treatment enalapril. The kicker? Using Entresto in all patients likely to benefit would save 28,484 lives per year.

In two articles published by JAMA Cardiology, separate groups of researchers analyzed data on U.S. heart failure patients and created mathematical models to test Entresto’s potential benefits for those who’d be eligible for the drug. Both studies assumed that all patients would see results in the real world similar to those Entresto delivered in clinical trials.

In one study, the researchers decided that 84% of heart failure patients with reduced ejection fraction--the population Entresto is approved to treat--would be eligible for therapy with Entresto. That’s almost 2.3 million patients. Using the drug properly in these patients could prevent 28,484 deaths every year, the study concluded, or a range of 18,230 to 41,017 per year.

The new drug "would have a substantial impact on the number of deaths happening for this patient population," study author Dr. Greg Foranow, of the UCLA Cardiomyopathy Center, told FiercePharma Thursday. "It's a clinically relevant result indicating a substantial impact on heart failure in the U.S."

"Proper" use wouldn't just include prescribing the drug to all the right patients, but the same type of care given to clinical trial patients, such as titrating to the right dose and monitoring kidney function as needed. Foranow said that assuming that standard of treatment is appropriate, given the data on previously adopted drugs, such as ACE inhibitors, and their real-world performance compared with clinical trial data.

The other study added hospitalizations into the mix. Researchers followed patients from a population model for 27 months and projected lifetime outcomes, and then weighed the cost of drug therapy with Entresto or enalapril, plus any medical expenses. They found that, for every 1,000 patients treated with Entresto, 220 hospitalizations would be averted over the course of their lifetimes. But the savings weren’t considered to be that simple: Because the enalapril patients were projected to die sooner than those on Entresto, the lifetime difference in hospitalizations was smaller, about 59. 

Overall, 1,000 patients taking Entresto would account for $4.4 million in increased drug costs compared with enalapril, the researchers said, and the reduction in hospitalization costs for those Entresto patients would be $1.4 million, comparatively. So, the absolute costs weren’t lower with Entresto. But under a common measure of cost-effectiveness--the quality-adjusted life year--the drug still delivered. Compared with common cardiac interventions already considered worthwhile, Entresto therapy came in as a “good value” under ACC/AHA standards.

"It's very rare that a new therapy would be cost-dominant, with benefits so overwhelming that they reduce total healthcare costs.  Here the reduction in hospitalization costs offset the drug costs but not completely," Foranow said.

But the QALY calculations fell far below the $50,000-per-QALY cost-effectiveness threshold that AHA adopted years ago, Foranow said, with numbers comparable to statin therapy--back when those cholesterol-fighters were only available as branded drugs. Implantable cardioverter defibrillators or desynchronization therapy are both examples of other "high-value" treatments.

The QALY calculations in this new study line up with similar analyses by the Institute for Clinical and Economic Review, which also questioned any savings in absolute costs, but deemed Entresto a good value for its $4,600-per-year price tag--and a better one after assuming discounts offered to payers in exchange for formulary placement.

The two studies follow up on new, unexpectedly strong recommendations from the American Heart Association and American College of Cardiology. Last month, the organizations rolled out heart failure treatment guidelines that not only back Entresto, but advise doctors to switch certain patients to the drug.

Novartis designed its Entresto development program not only to win regulatory approval, but also to answer one important question from payers: Will this drug be worth the cost? The heart failure med had seemed to do just that by reducing expensive hospitalizations in the big PARADIGM trial.

"PARADIGM-HF was pretty compelling, not just for reducing cardiac death, but all-cause mortality," Foranow said.

But Entresto has been a tough sell even so. With cheap generics as the current standard of care, payers have put prior authorization hurdles and higher copays on Entresto, hobbling uptake. Some doctors have said they’re reluctant to switch stable patients over to the Novartis treatment, despite the PARADIGM data.

The new treatment guidelines could help sway doctors, and payers, toward the Novartis drug. But Novartis isn’t taking any chances; it’s rolling out a slate of new studies for Entresto--dubbed FortiHFy--to generate new data for payers and regulators. One trial will test the drug as a heart-failure prevention tool, using it in patients at high risk of heart failure after a heart attack. Another will pit Entresto, a combination drug, against the Novartis blood pressure treatment that’s one of its ingredients, valsartan.

In the meantime, Novartis can try to make hay with its new ACC/AHA guidelines recommendation and the latest from JAMA. But Foranow said that uptake of new treatments, despite strong evidence that they work, historically has been poor. "You see huge delays, huge gaps, huge variations in how they're applied in clinical practice," he said, adding that the guidelines, along with some systematic efforts to implement new treatment standard--plus studies like the two published in JAMA--could help speed adoption.

Analysts and investors will be watching: Even before Novartis announced disappointing Q1 sales for the product, analysts had started slashing their blockbuster projections.

Entresto sales estimates “have been marked down substantially in recent months, given the anemic initial launch trajectory of the product,” Bernstein analyst Tim Anderson wrote after the ACC and AHA backed Entresto. “These new guidelines should be a relief to investors and support the idea that, while perhaps not as big as some analysts had originally hoped for, over time Entresto is still likely to become a very meaningful product.”

- get the JAMA Cardiology mortality study
- see the JAMA cost-effectiveness study

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