Novartis aims to jump-start Entresto with new round of clinical trials

Joe Jimenez

When Novartis designed its clinical trials for the heart failure drug Entresto, it did so with payers in mind: It included an endpoint--hospitalizations--in hopes of showing that the drug could keep patients out of the hospital, and save money in the process.

But so far, that data hasn’t been enough to win quick, unqualified reimbursement for the med, not when cheap generics have been the standard of care.

Now, the Swiss drugmaker is putting more money into investigating Entresto’s ability to deliver the kind of payoffs that insurers want. It’s rolling out a new clinical program, FortiHFy, to generate new data, including real-world results and quality-of-life benefits. The data could not only bolster Entresto’s current case, but help the drug expand into new indications--and thus a bigger target market.

One trial, Paradise-MI, is even testing Entresto as a heart failure preventative. The study will use Entresto in patients at high risk of heart failure after a heart attack, to see whether the drug reduces cardiovascular death and new heart failure diagnoses. Others will look at beginning Entresto therapy while patients are still in the hospital, rather than after. One will test the drug against valsartan, otherwise known as the Novartis blood pressure med Diovan, which is one of Entresto’s active ingredients.

The program will comprise 40 studies in all. “FortiHFy … reinforces our long term commitment to improving heart failure treatment for as many people as possible," said Novartis CMO Vas Narasimhan said in a statement. "The outcomes of these trials will increase our understanding of heart failure, the patient population who may benefit from Entresto, and could potentially support applications to regulatory authorities.”

Entresto has been something of a disappointment so far. The company had hoped it would gain momentum more quickly, particularly with the outcomes data it had in hand. But payers were slow to negotiate reimbursement deals, and Medicare--whose patients form a big chunk of Entresto’s target population--took the full six months allotted to make its decisions.

The drug has faltered a bit with physicians as well, causing one analyst to cut his peak sales estimate for the drug--previously $6 billion--in half. "As we see it, the biggest challenges to clinical adoption are reluctance to switch the group of stable patients as well as titration and hypotension issues," Leerink Partners analyst Seamus Fernandez said.

Novartis says it’s still expecting Entresto to soar in the blockbuster sphere, and it’s looking for $200 million in sales this year. The fact that it’s putting more money into trials shows that Novartis is both confident that the investment will pay off--and cognizant of the fact that Entresto may need some additional evidence to back up its bid for market share.

The company was already studying Entresto in other patient groups, hoping to broaden its base beyond the current indication--treating symptomatic heart failure patients with systolic dysfunction. For one, patients with preserved ejection fraction, rather than reduced, as in its current approval.

To be fair, payer pressure is hampering other new launches as well, particularly the PCSK9 cholesterol-fighters launched last year by Amgen (Repatha), and Sanofi and Regeneron (Praluent). The slow uptake for those meds--as well as Entresto--prompted Novartis CEO Joe Jimenez to predict a new normal for U.S. drug rollouts.

“It’s going to be a fact of life that we have to accept a slower uptake,” Jimenez told the Financial Times last month. “The model has changed and it will take longer to get up and running.”

- see the Novartis release

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